NeoplasmsPhase 1NCT02215096

Dose-finding Study of GSK2636771 When Administered in Combination With Enzalutamide in Male Subjects With Metastatic Castration-Resistant Prostate Cancer

A Phase 1 study testing GSK2636771 and Enzalutamide in people with Neoplasms, run by GlaxoSmithKline at 9 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and older, men only
Conditions the study is for: Neoplasms
What is being tested?: GSK2636771 and Enzalutamide
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 37 participants
Where: 9 sitesin 2 countries
Study dates: 13 Nov 2014to 3 Oct 2019
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
Men only
No healthy volunteers
Adult, Older adult

Who may be able to join

Signed written informed consent provided
Males >=18 years of age (at the time consent is obtained)
Histologically or cytologically confirmed diagnosis of prostate adenocarcinoma, surgically castrated or continuous medical castration (for >=8 weeks prior to Screening)
Serum testosterone <50 nanogram per deciliter (ng/dL) (1.7 nanomole per liter [nM/L])
PTEN deficient tumor as documented from archival or fresh (from biopsy) tumor tissue analyzed by GlaxoSmithKline selected laboratory
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

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Completed at least 12 weeks of prior continuous therapy with enzalutamide. A 2 week or less treatment (enzalutamide) holiday will be permitted prior to initiating study treatment.
Most recent enzalutamide dose received is 160 mg once daily with no change in dose for at least 2 weeks prior to Screening.
Has progressive disease at time of enrollment defined as one or more of the following criteria: PSA progression defined by PCWG2 criteria or soft tissue disease progression defined by RECIST 1.1 or bone disease progression defined by PCWG2 criteria Able to swallow and retain orally administered medication.
Adequate baseline organ function.
Must have a QT interval corrected for heart rate according to Fridericia's formula (QTcF) <470 milli seconds (msec) or <480 msec with bundle branch block.
Male subject with a female partner of childbearing potential must have either had a prior vasectomy or agree to use effective contraception from time of Screening until 3 months after the last dose of study treatment.

Who cannot join

Prior treatment with: anti-cancer therapy (e.g., chemotherapy with delayed toxicity, immunotherapy, biologic therapy or chemoradiation) within 21 days (or within 42 days if prior nitrosourea or mitomycin C containing therapy) prior to enrollment and/or daily or weekly chemotherapy without the potential for delayed toxicity within 14 days prior to enrolment. Subjects may remain on luteinizing hormone releasing hormone (LHRH) agonists (i.e., leuprolide, goserelin, triptorelin or histrelin). Subjects must have prior enzalutamide treatment; Any PI3K, AKT or mammalian target of rapamycin (mTOR) inhibitors; Investigational drug(s) within 30 days or 5 half-lives, whichever is longer, prior to enrollment
Prior malignancy other than CRPC. Subjects who have been disease-free for 5 years, or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible.
Current use of or anticipated requirement during the study of prohibited medication(s) (any investigational drug(s), Other anti-cancer therapy (chemotherapy, radiation therapy, immunotherapy, biologic therapy, or hormone therapy other than for replacement), AR antagonists (e.g., bicalutamide, flutamide, nilutamide), 5-alpha reductase inhibitors (e.g., finasteride, dutasteride), Androgens (e.g., testosterone, dihydroepiandrosterone), Herbal medication(s) that may affect PSA levels (e.g., saw palmetto), Other herbal medications including, but not limited to: St. John's wort, kava, ephedra (ma huang), gingko biloba, yohimbe and ginseng)
Any unresolved >=Grade 2 (per CTCAE v 4.0) toxicity from previous anti-cancer therapy at the time of enrollment, except alopecia or Grade 2 anemia (if hemoglobin is >9.0 g/dL)
Any >=Grade 2 hypophosphatemia (per CTCAE v4.0) at the time of enrolment
Serum calcium >=Grade 1 (per CTCAE v4.0) at time of enrolment, unless ionized calcium is within normal range

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Presence of any clinically significant gastrointestinal (GI) abnormality or other condition(s) that may alter absorption such as malabsorption syndrome or major resection of the stomach or substantial portion of the small intestine
Active peptic ulcer disease or history of abdominal fistula, GI perforation, or intra abdominal abscess within 28 days prior to enrolment
Previous major surgery within 28 days prior to enrolment
Known active infection requiring intravenous (IV) or oral anti-infective treatment
Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment.
A positive pre-study drug/alcohol screening (testing at time of screening is not required).
A positive test for human immunodeficiency virus (HIV) antibody (testing at time of screening is not required).
Evidence of severe or uncontrolled systemic diseases (e.g., unstable or uncompensated respiratory, hepatic, renal or cardiac disease)
History of seizure or any condition that may predispose subject to seizure (e.g., prior cortical stroke or significant brain trauma). History of loss of consciousness or transient ischemic attack within 12 months of randomization
History or evidence of cardiovascular risk including any of the following: Clinically significant electrocardiogram abnormalities including second degree (Type II) or third degree atrioventricular block; history of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, stenting, or bypass grafting within the past 6 months prior to enrolment, Class III or IV heart failure as defined by the New York Heart Association functional classification system, LVEF below 50%; known cardiac metastases
Poorly controlled hypertension (defined as systolic blood pressure of>=150 millimeter of mercury (mmHg) or diastolic blood pressure of >100 mmHg based on a mean of three measurements at approximately 2-minute intervals)
History of congenital platelet function defect (e.g., Bernard-Soulier syndrome, Chediak-Higashi syndrome, Glanzmann thrombasthenia, storage pool defect)
Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to GSK2636771or enzalutamide or excipients.
Any serious and/or unstable pre-existing medical, psychiatric disorder or other conditions that could interfere with subject's safety, obtaining informed consent or compliance to the study procedures.
Exposure to more than 4 investigational medicinal products within 12 months prior to the first dose of study treatment

Trial locations and contacts

9 sites in 2 countries.

Country

City, postcode or hospital

9 sites in 2 countries

United States7 sites

GSK Investigational Site
Detroit, Michigan, 48201
GSK Investigational Site
Duarte, California, 91010
GSK Investigational Site
Houston, Texas, 77030
GSK Investigational Site
Los Angeles, California, 90033
GSK Investigational Site
Los Angeles, California, 90095
GSK Investigational Site
New York, New York, 10016
GSK Investigational Site
Washington D.C., District of Columbia, 20007

Other trials in United States

United Kingdom2 sites

GSK Investigational Site
London, SE1 9RT
GSK Investigational Site
Sutton, SM2 5PT

Other trials in United Kingdom

About this study

Official title: A Phase I, Open-label, Dose-finding Study of GSK2636771 Administered in Combination With Enzalutamide (Xtandi^TM ) in Male Subjects With Metastatic Castration-Resistant Prostate Cancer (mCRPC)

This Phase I, open-label, dose-finding, multicenter study is designed to determine the recommended Phase II dose (RP2D) for the combination of an orally administered Phosphatidylinositol-4,5-bisphosphate 3-kinase beta (PI3K-beta) inhibitor (GSK2636771) with enzalutamide. Subjects with phosphatase and tensin homolog (PTEN)-deficient metastatic castration-resistant prostate cancer (mCRPC) who are receiving a stable dose of enzalutamide with a recently demonstrated progression (either by RECIST [Response Evaluation Criteria In Solid Tumors] version 1.1, prostate-specific antigen [PSA] progression, and/or progression in bone) per the Prostate Cancer Working Group 2 (PCWG2) criteria will be enrolled. Eligible subjects will be enrolled in the Dose-Escalation Phase to determine the maximum tolerated dose (MTD) of the combination therapy using a modified 3+3 dose escalation procedure. The safety, pharmacokinetics (PK) and clinical efficacy will also be assessed to guide the selection of the RP2D. The starting dose will be GSK2636771 300 mg once daily in combination with the recommended dose (160 milligram [mg] once daily) of oral enzalutamide. Once the RP2D has been established, additional subjects will be enrolled in the Dose Expansion Phase to further evaluate the safety, PK and preliminary clinical activity. Safety assessments will be performed throughout the study including physical examinations, vital signs, clinical laboratory tests, 12 lead electrocardiograms and monitoring of adverse events. Blood samples will be collected for pharmacokinetic analysis. Subjects will continue treatment until an unacceptable toxicity, disease progression, withdrawal of consent or death occurs. A post-treatment follow-up visit will be performed within 30 days of the last dose of study treatment. Xtandi is a registered trademark of Astellas Pharma Inc

Conditions: Neoplasms
Being tested: GSK2636771, Enzalutamide
Keywords: enzalutamide, metastatic castration-resistant prostate cancer, GSK2636771, PI3K-beta, PTEN deficiency
Medical subject headings: Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

GSK2636771Drug
GSK is available as 100 mg hard gelatin oral capsule to be taken once daily/continuous until treatment withdrawal under fasting conditions for at least 1hour (h) before and 2h after dosing with approximately 200 mL of water
EnzalutamideDrug
Enzalutamide will be sourced locally from commercial stock for sites in countries where it is approved

Study groups in NCT02215096
Study group	Role	What they receive
Phase 1-Dose Escalation	Experimental	Subject receiving a stable dose of enzalutamide 160 mg once daily will receive GSK2636771 following a modified 3+3 dose escalation procedure (Cohort -1: 200 mg, Cohort 1: 300 mg and Cohort 2: 400 mg) to evaluate the safety and PK for each combination dose level and to guide selection of the RP2D of the combination. If the combination doses in Cohort 1 are not tolerable, lower doses as defined in the de-escalation cohort (Cohort -1) will be evaluated. If the de-escalation cohort (Cohort -1) is not tolerable, further dose-escalation using a continuous daily dosing schedule for both compounds simultaneously will be terminated. Additional dose levels of GSK2636771 or alternative dosing schedules may be explored based upon ongoing assessment of safety and PK. Dose modification decisions will be made utilizing all available data at the end of each DLT determination period (28 days). Receives: Drug: GSK2636771; Drug: Enzalutamide
Phase 2- Dose Expansion	Experimental	Additional 20 subjects will be assigned to receive GSK2636771 at the MTD or RP2D determined in the Dose-Escalation Phase while continuing treatment with enzalutamide to evaluate the long-term safety of the combination as well as the 12-week non-PD rate Receives: Drug: GSK2636771; Drug: Enzalutamide

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs) During run-in Period
An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participants, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, protocol-specific SAEs: All events of possible study treatment-induced liver injury with hyperbilirubinemia defined as alanine aminotransferase (ALT) >=3 times upper limit of normal (ULN), and bilirubin >=2 times ULN (>35 percent [%] direct) (or ALT >=3 times ULN and international normalized ratio (INR) >1.5 if INR is measured) or termed 'Hy's Law' events (INR measurement is not required and the threshold value stated did not apply to participants receiving anticoagulants) or any new primary cancer.
Measured: Up to Week 2
Number of Participants With Non-SAEs and SAEs During Combination Treatment Period
An AE is any untoward medical occurrence in a participant or clinical investigation participants, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, protocol-specific SAEs: All events of possible study treatment-induced liver injury with hyperbilirubinemia defined as ALT >=3 times ULN, and bilirubin >=2 times ULN (>35% direct) (or ALT >=3 times ULN and INR >1.5 if INR is measured) or termed 'Hy's Law' events (INR measurement is not required and the threshold value stated did not apply to participants receiving anticoagulants) or any new primary cancer.
Measured: Up to maximum 675 days
Number of Participant With Dose-limiting Toxicities (DLT) During Combination Treatment Period
An event was considered as DLT if the event was attributed (definitely, probably or possibly) to study treatment, occured within the first 28 days of combination treatment (DLT reporting period), and met one of the following criteria: Febrile neutropenia of any grade or duration as per Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, Grade 4 neutropenia lasting >5 days, Grade 3 or greater non-hematologic toxicity that cannot be controlled with routine supportive measures, Grade 4 thrombocytopenia, ALT >3 times ULN with bilirubin >2 times ULN or ALT >=3 times ULN and >=1.5 times Baseline ALT value, if enrolled with liver metastases/tumor infiltration at Baseline), together with bilirubin >=2 times ULN.
Measured: Up to Day 28
Percent Change From Baseline in Hematology Parameters During Combination Treatment Period: Basophils, Eosinophils, Hematocrit, Hemoglobin, Lymphocytes, MCH, MCV, Monocytes, Total Neutrophils, Platelet Count, WBC Count
Blood samples were collected to analyze the hematology parameters: basophils, eosinophils, hematocrit, hemoglobin, lymphocytes, mean corpuscular hemoglobin (MCH), mean corpuscular volume (MCV), monocytes, total neutrophils, platelet count and white blood cells (WBCs) count. Baseline value is the latest GSK2636771 pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Percent change from Baseline was calculated as 100 multiplied by (post-Baseline visit value minus Baseline divided by Baseline).
Measured: Baseline (Day 1), Weeks 2,3,4,5,8,12,16,20,24,28,32,36,40,44,48,52,56,60,64,68,72,76,80,84 and 88
Percent Change From Baseline in Hematology Parameters During Combination Treatment Period: International Normalized Ratio (INR), Prothrombin Time (PT), Partial Thromboplastin Time (PTT)
Blood samples were collected to analyze the hematology parameters: INR, PT and PTT. Baseline value is the latest GSK2636771 pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Percent change from Baseline was calculated as 100 multiplied by (post-Baseline visit value minus Baseline divided by Baseline).
Measured: Baseline (Day 1), Week 4
Percent Change From Baseline in Chemistry Parameters in Combination Treatment Period:ALT, Albumin, ALP, AST, Calcium, CO2, Chloride, Creatinine, Direct Bilirubin, Glucose, Lactate Dehydrogenase, Magnesium, Potassium, Sodium, Total Bilirubin, Total Protein
Blood samples were collected to analyze the chemistry parameters: ALT, Albumin, Alkaline phosphatase (ALP), Aspartate amino transferase (AST), Calcium, Carbon dioxide (CO2), Chloride, Creatinine, Direct bilirubin, Glucose, Lactate dehydrogenase, Magnesium, Potassium, Sodium, Total bilirubin and Total protein. Baseline value is the latest GSK2636771 pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Percent change from Baseline was calculated as 100 multiplied by (post-Baseline visit value minus Baseline divided by Baseline).
Measured: Baseline (Day 1), Weeks 1,2,3,4,5,8,12,16,20,24,28,32,36,40,44,48,52,56,60,64,68,72,76,80,84 and 88
Percent Change From Baseline in Chemistry Parameters During Combination Treatment Period: Blood Urea Nitrogen (BUN), Uric Acid
Blood samples were collected to analyze the chemistry parameters: BUN and uric acid. Baseline value is the latest GSK2636771 pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Percent change from Baseline was calculated as 100 multiplied by (post-Baseline visit value minus Baseline divided by Baseline).
Measured: Baseline (Day 1), Weeks 1, 2,3,4,5,8,12,16,20,24,28,32,36,40,44,48,52,56,60,64,68,72,76,80,84 and 88
Percent Change From Baseline in Urine Concentration of Calcium, Creatinine Concentration, Magnesium, Phosphate, Protein During Combination Treatment Period
Urine samples were collected to analyze the urinalysis parameters: Calcium, Creatinine concentration (conc), Magnesium, Phosphate and Protein. Baseline value is the latest GSK2636771 pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Percent change from Baseline was calculated as 100 multiplied by (post-Baseline visit value minus Baseline divided by Baseline).
Measured: Baseline (Day 1), Weeks 1, 3, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 48, 56 and 64
Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings During Combination Treatment Period
A 12-lead ECG was obtained after the participant had rested at least 5 minutes in a semi-recumbent or supine position at each time point during the study using ECG machine that automatically measured PR, QRS, QT and Corrected QT interval (QT duration corrected for heart rate by Bazett's formula [QTcB] and Fridericia's formula [QTcF]). Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Number of participants with abnormal clinical significant ECG findings are presented.
Measured: Weeks 4, 8, 16, 24, 32, 40, 48, 56, 64, 72, 80 and 88
Number of Participants With Worst Case Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Results by Maximum Grade Increase Post-Baseline Relative to Baseline During Combination Treatment Period
SBP and DBP were measured after resting for 5 minutes in semi-supine position. SBP and DBP were graded according to Common Toxicity Criteria for Adverse Events (CTCAE) version 4. 'Any grade increase' is defined as an increase in CTCAE grade relative to Baseline grade. For SBP, Grade 0: <120 millimeters of mercury [mmHg]), Grade 1: 120-139 mmHg, Grade 2: 140-159 mmHg, Grade 3:>=160 mmHg. For DBP, Grade 0: <80 mmHg, Grade 1: 80-89 mmHg, Grade 2: 90-99 mmHg, Grade 3: >=100 mmHg. Higher grade indicate worst outcome. Data for worst-case post-Baseline is reported.
Measured: Up to maximum 654 days
Number of Participants With Worst Case Post-Baseline Results for Heart Rate During Combination Treatment Period
Heart rate was measured after resting for 5 minutes in semi-supine position. The clinical concern range for heart rate was: low: decrease to <60 beats per minute (bpm) and high: increase to >100 bpm. Participants were counted in the worst case category that their value changed to (low, within range or no change, or high) unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the 'Change to normal or No Change' category. Participants were counted twice if the participant had both values 'decrease to <60 bpm' and 'increase to >100 bpm' during post-Baseline visits. Data for worst case post-Baseline is reported.
Measured: Up to maximum 654 days
Number of Participants With Worst Case Post-Baseline Results for Body Temperature During Combination Treatment Period
Temperature was measured after resting for 5 minutes in semi-supine position. The clinical concern range for body temperature was: low: decrease to <=35 degrees celsius, high: increase to >=38 degrees celsius. Participants were counted in the worst case category that their value changed to (low, within range or no change, or high) unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the 'Change to normal or No Change' category. Participants were counted twice if the participant had both values 'decreased to <=35 degree celsius' and 'increased to >=38 degrees celsius' during post-Baseline visits. Data for worst-case post-Baseline is presented.
Measured: Up to maximum 654 days
Non-progressive Disease (Non-PD) Rate at Week 12 According to Prostate Cancer Working Group 2 (PCWG2) Criteria in GSK2636771 200mg/Enzalutamide 160mg - Overall Arm
The 12-week non-PD rate was defined as percentage of participants without progression(non-PD) at Week12 as determined from Prostate-specific antigen(PSA) results, radiographic assessment per Response Evaluation Criteria In Solid Tumors(RECIST)1.1 and bone scan.Disease progression was defined by 1 or more of the following:PSA progression alone; PSA progression according to the PCWG2 criteria with accompanying progression by RECIST1.1 or bone scan for participants with soft tissue Baseline disease; Bone progression on bone scan according to PCWG2 criteria; or Radiographic progression in soft tissue or bone by RECIST1.1 for participants with Baseline disease.Modified All Treated Clinical Activity Population consisted of all participants who received at least 1 dose of GSK2636771 and who were treated at the same dose as dose expansion cohort and have been on study drug for at least 12weeks or have discontinued study treatment due to disease progression, died or withdrawn for any reason.
Measured: At Week 12

Secondary outcomes (11)

Prostate-specific Antigen Decrease From Baseline >=50% (PSA50) Response Rate at 12 Weeks During Combination Treatment Period
PSA50 response rate is defined as percentage of participants with a decrease of >=50% in the PSA concentration from the Baseline PSA value determined at least 12 weeks after start of treatment until last post-treatment follow-up visit or initiation of new anti-cancer therapy and confirmed after 3 or more weeks by an additional PSA evaluation. Confirmed PSA50 is defined as decline of >=50% in PSA concentration from Baseline.
Measured: At Week 12
Objective Response Rate (ORR) During Combination Treatment Period
ORR is defined as the percentage of participants with a confirmed complete response (CR) or a partial response (PR) as the Best Overall Response (BOR), as assessed by the investigator per RECIST Version (v) 1.1 criteria; where CR: Disappearance of all target lesions; PR: at least 30% decrease in the sum of the longest diameter of target lesions with reference to Baseline sum of diameters.
Measured: Up to maximum 654 days
Time to PSA Progression According to PCWG2 Criteria During Combination Treatment Period
Time to PSA progression is defined as the time from combination study treatment start until the first PSA progression per PCWG2 criteria (confirmed if there has been a PSA decline from Baseline). Time to PSA was analyzed using Kaplan-Meier methods. Median and inter-quartile range (first and third quartile) are presented.
Measured: Up to maximum 654 days
Time to Radiological Progression According to PCWG2 Criteria During Combination Treatment Period
Time to radiological progression is defined as the time from combination study treatment start until the first radiological progression by PCWG2 criteria. Time to radiological progession was analyzed using Kaplan-Meier methods. For participants who do not progress, participants were censored at the time of last radiological scan or date of death. Participants who discontinued study with no post-treatment tumor assessment were censored at date of first dose of GSK2636771 drug. Median and inter-quartile range (first and third quartile) are presented.
Measured: Up to maximum 654 days
Radiological Progression Free Survival (rPFS) Per PCWG2 Criteria During Combination Treatment Period
rPFS is defined as the interval of time (in weeks) between the date of first dose of GSK2636771 and the earlier of the date of disease progression as assessed by the investigator per RECIST version 1.1 criteria and the date of death due to any cause. For participants who do not progress or die, participants were censored at the time of last radiological scan. Participants who discontinued study with no post-treatment tumor assessment were censored at date of first dose of GSK2636771 drug. rPFS was analyzed using Kaplan-Meier methods. Median and inter-quartile range (first and third quartile) are presented.
Measured: Up to maximum 654 days
Plasma Concentration of GSK2636771 in GSK2636771/Enzalutamide Expansion Cohort in Combination Treatment Period
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2636771.
Measured: Week 5: Pre-dose, 1, 2, 3, 5-6, 6-7, 7-8 hours post-dose; Weeks 8 and 12: Pre-dose
Plasma Concentration of GSK2636771 in GSK2636771/Enzalutamide Escalation Cohorts in Combination Treatment Period
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2636771. Pharmacokinetic Concentration Population consisted of all participants in the All Treated Safety Population for whom a blood sample for pharmacokinetics were obtained, analyzed, and was measurable.
Measured: Week 5: Pre-dose, 0.5, 1, 2, 3, 4, 6 hours post-dose; Weeks 8 and 12: Pre-dose
Plasma Concentration of Enzalutamide in GSK2636771/Enzalutamide Escalation Cohorts in Combination Treatment Period
Blood samples were collected at indicated time points for pharmacokinetic analysis of enzalutamide.
Measured: Week 5: Pre-dose, 0.5, 1, 2, 3, 4, 6 hours post-dose; Weeks 8 and 12: Pre-dose
Plasma Concentration of Enzalutamide in GSK2636771/Enzalutamide Expansion Cohort in Combination Treatment Period
Blood samples were collected at indicated time points for pharmacokinetic analysis of enzalutamide.
Measured: Week 5: Pre-dose, 1, 2, 3, 5-6, 6-7, 7-8 hours post-dose; Weeks 8 and 12: Pre-dose
Plasma Concentration of N-desmethyl Enzalutamide in GSK2636771/Enzalutamide Escalation Cohorts in Combination Treatment Period
Blood samples were collected at indicated time points for pharmacokinetic analysis of N-desmethyl enzalutamide.
Measured: Week 5: Pre-dose, 0.5, 1, 2, 3, 4, 6 hours post-dose; Weeks 8 and 12: Pre-dose
Plasma Concentration of N-desmethyl Enzalutamide in GSK2636771/Enzalutamide Expansion Cohort in Combination Treatment Period
Blood samples were collected at indicated time points for pharmacokinetic analysis of N-desmethyl enzalutamide.
Measured: Week 5: Pre-dose, 1, 2, 3, 5-6, 6-7, 7-8 hours post-dose; Weeks 8 and 12: Pre-dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

13 Nov 20143 Oct 2019

First posted13 Aug 2014 (estimated)
Study start13 Nov 2014
Primary completion3 Oct 2019
Study completion3 Oct 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for NeoplasmsStudies of the same condition, open and under way.
More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Enrolment: 37 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02215096
Sponsor's protocol ID: 200331
Other IDs: 2013-005111-27
Status last verified: Sep 2020
First submitted: 11 Aug 2014
Last updated: 22 Oct 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Sarker D, Dawson NA, Aparicio AM, Dorff TB, Pantuck AJ, Vaishampayan UN, Henson L, Vasist L, Roy-Ghanta S, Gorczyca M, York W, Ganji G, Tolson J, de Bono JS. A Phase I, Open-Label, Dose-Finding Study of GSK2636771, a PI3Kbeta Inhibitor, Administered with Enzalutamide in Patients with Metastatic Castration-Resistant Prostate Cancer. Clin Cancer Res. 2021 Oct 1;27(19):5248-5257. doi: 10.1158/1078-0432.CCR-21-1115.
PubMed 34281912

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Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 22 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase I, Open-label, Dose-finding Study of GSK2636771 Administered in Combination With Enzalutamide (Xtandi^TM ) in Male Subjects With Metastatic Castration-Resistant Prostate Cancer (mCRPC)
ClinicalTrials.gov ID: NCT02215096
Acronym / sponsor ID: 200331
Conditions: Neoplasms
Keywords: enzalutamide, metastatic castration-resistant prostate cancer, GSK2636771, PI3K-beta, PTEN deficiency
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 37 participants (actual)
Lead sponsor: GlaxoSmithKlineIndustry (pharma, biotech, devices)
Study start: 13 Nov 2014 (actual)
Primary completion: 3 Oct 2019 (actual)
Study completion: 3 Oct 2019 (actual)
First posted: 13 Aug 2014 (estimated)
Results: Posted 22 Oct 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Phase 1-Dose Escalation	Experimental	Drug: GSK2636771, Drug: EnzalutamideSubject receiving a stable dose of enzalutamide 160 mg once daily will receive GSK2636771 following a modified 3+3 dose escalation procedure (Cohort -1: 200 mg, Cohort 1: 300 mg and Cohort 2: 400 mg) to evaluate the safety and PK for each combination dose level and to guide selection of the RP2D of the combination. If the combination doses in Cohort 1 are not tolerable, lower doses as defined in the de-escalation cohort (Cohort -1) will be evaluated. If the de-escalation cohort (Cohort -1) is not tolerable, further dose-escalation using a continuous daily dosing schedule for both compounds simultaneously will be terminated. Additional dose levels of GSK2636771 or alternative dosing schedules may be explored based upon ongoing assessment of safety and PK. Dose modification decisions will be made utilizing all available data at the end of each DLT determination period (28 days).
Phase 2- Dose Expansion	Experimental	Drug: GSK2636771, Drug: EnzalutamideAdditional 20 subjects will be assigned to receive GSK2636771 at the MTD or RP2D determined in the Dose-Escalation Phase while continuing treatment with enzalutamide to evaluate the long-term safety of the combination as well as the 12-week non-PD rate

Who may qualify

Ages: 18 years and older
Sex: Male only
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (12 listed)

Signed written informed consent provided
Males >=18 years of age (at the time consent is obtained)
Histologically or cytologically confirmed diagnosis of prostate adenocarcinoma, surgically castrated or continuous medical castration (for >=8 weeks prior to Screening)
Serum testosterone <50 nanogram per deciliter (ng/dL) (1.7 nanomole per liter [nM/L])
PTEN deficient tumor as documented from archival or fresh (from biopsy) tumor tissue analyzed by GlaxoSmithKline selected laboratory

Key exclusion criteria (21 listed)

Prior treatment with: anti-cancer therapy (e.g., chemotherapy with delayed toxicity, immunotherapy, biologic therapy or chemoradiation) within 21 days (or within 42 days if prior nitrosourea or mitomycin C containing therapy) prior to enrollment and/or daily or weekly chemotherapy without the potential for delayed toxicity within 14 days prior to enrolment. Subjects may remain on luteinizing hormone releasing hormone (LHRH) agonists (i.e., leuprolide, goserelin, triptorelin or histrelin). Subjects must have prior enzalutamide treatment; Any PI3K, AKT or mammalian target of rapamycin (mTOR) inhibitors; Investigational drug(s) within 30 days or 5 half-lives, whichever is longer, prior to enrollment
Prior malignancy other than CRPC. Subjects who have been disease-free for 5 years, or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible.
Current use of or anticipated requirement during the study of prohibited medication(s) (any investigational drug(s), Other anti-cancer therapy (chemotherapy, radiation therapy, immunotherapy, biologic therapy, or hormone therapy other than for replacement), AR antagonists (e.g., bicalutamide, flutamide, nilutamide), 5-alpha reductase inhibitors (e.g., finasteride, dutasteride), Androgens (e.g., testosterone, dihydroepiandrosterone), Herbal medication(s) that may affect PSA levels (e.g., saw palmetto), Other herbal medications including, but not limited to: St. John's wort, kava, ephedra (ma huang), gingko biloba, yohimbe and ginseng)
Any unresolved >=Grade 2 (per CTCAE v 4.0) toxicity from previous anti-cancer therapy at the time of enrollment, except alopecia or Grade 2 anemia (if hemoglobin is >9.0 g/dL)
Any >=Grade 2 hypophosphatemia (per CTCAE v4.0) at the time of enrolment

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
GSK2636771GSK is available as 100 mg hard gelatin oral capsule to be taken once daily/continuous until treatment withdrawal under fasting conditions for at least 1hour (h) before and 2h after dosing with approximately 200 mL of water	Drug	Phase 1-Dose Escalation, Phase 2- Dose Expansion
EnzalutamideEnzalutamide will be sourced locally from commercial stock for sites in countries where it is approved	Drug	Phase 1-Dose Escalation, Phase 2- Dose Expansion

Primary outcome

Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs) During run-in Period
Time frame: Up to Week 2
An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participants, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, protocol-specific SAEs: All events of possible study treatment-induced liver injury with hyperbilirubinemia defined as alanine aminotransferase (ALT) >=3 times upper limit of normal (ULN), and bilirubin >=2 times ULN (>35 percent [%] direct) (or ALT >=3 times ULN and international normalized ratio (INR) >1.5 if INR is measured) or termed 'Hy's Law' events (INR measurement is not required and the threshold value stated did not apply to participants receiving anticoagulants) or any new primary cancer.
Number of Participants With Non-SAEs and SAEs During Combination Treatment Period
Time frame: Up to maximum 675 days
An AE is any untoward medical occurrence in a participant or clinical investigation participants, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, protocol-specific SAEs: All events of possible study treatment-induced liver injury with hyperbilirubinemia defined as ALT >=3 times ULN, and bilirubin >=2 times ULN (>35% direct) (or ALT >=3 times ULN and INR >1.5 if INR is measured) or termed 'Hy's Law' events (INR measurement is not required and the threshold value stated did not apply to participants receiving anticoagulants) or any new primary cancer.
Number of Participant With Dose-limiting Toxicities (DLT) During Combination Treatment Period
Time frame: Up to Day 28
An event was considered as DLT if the event was attributed (definitely, probably or possibly) to study treatment, occured within the first 28 days of combination treatment (DLT reporting period), and met one of the following criteria: Febrile neutropenia of any grade or duration as per Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, Grade 4 neutropenia lasting >5 days, Grade 3 or greater non-hematologic toxicity that cannot be controlled with routine supportive measures, Grade 4 thrombocytopenia, ALT >3 times ULN with bilirubin >2 times ULN or ALT >=3 times ULN and >=1.5 times Baseline ALT value, if enrolled with liver metastases/tumor infiltration at Baseline), together with bilirubin >=2 times ULN.
Percent Change From Baseline in Hematology Parameters During Combination Treatment Period: Basophils, Eosinophils, Hematocrit, Hemoglobin, Lymphocytes, MCH, MCV, Monocytes, Total Neutrophils, Platelet Count, WBC Count
Time frame: Baseline (Day 1), Weeks 2,3,4,5,8,12,16,20,24,28,32,36,40,44,48,52,56,60,64,68,72,76,80,84 and 88
Blood samples were collected to analyze the hematology parameters: basophils, eosinophils, hematocrit, hemoglobin, lymphocytes, mean corpuscular hemoglobin (MCH), mean corpuscular volume (MCV), monocytes, total neutrophils, platelet count and white blood cells (WBCs) count. Baseline value is the latest GSK2636771 pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Percent change from Baseline was calculated as 100 multiplied by (post-Baseline visit value minus Baseline divided by Baseline).
Percent Change From Baseline in Hematology Parameters During Combination Treatment Period: International Normalized Ratio (INR), Prothrombin Time (PT), Partial Thromboplastin Time (PTT)
Time frame: Baseline (Day 1), Week 4
Blood samples were collected to analyze the hematology parameters: INR, PT and PTT. Baseline value is the latest GSK2636771 pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Percent change from Baseline was calculated as 100 multiplied by (post-Baseline visit value minus Baseline divided by Baseline).
Percent Change From Baseline in Chemistry Parameters in Combination Treatment Period:ALT, Albumin, ALP, AST, Calcium, CO2, Chloride, Creatinine, Direct Bilirubin, Glucose, Lactate Dehydrogenase, Magnesium, Potassium, Sodium, Total Bilirubin, Total Protein
Time frame: Baseline (Day 1), Weeks 1,2,3,4,5,8,12,16,20,24,28,32,36,40,44,48,52,56,60,64,68,72,76,80,84 and 88
Blood samples were collected to analyze the chemistry parameters: ALT, Albumin, Alkaline phosphatase (ALP), Aspartate amino transferase (AST), Calcium, Carbon dioxide (CO2), Chloride, Creatinine, Direct bilirubin, Glucose, Lactate dehydrogenase, Magnesium, Potassium, Sodium, Total bilirubin and Total protein. Baseline value is the latest GSK2636771 pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Percent change from Baseline was calculated as 100 multiplied by (post-Baseline visit value minus Baseline divided by Baseline).
Percent Change From Baseline in Chemistry Parameters During Combination Treatment Period: Blood Urea Nitrogen (BUN), Uric Acid
Time frame: Baseline (Day 1), Weeks 1, 2,3,4,5,8,12,16,20,24,28,32,36,40,44,48,52,56,60,64,68,72,76,80,84 and 88
Blood samples were collected to analyze the chemistry parameters: BUN and uric acid. Baseline value is the latest GSK2636771 pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Percent change from Baseline was calculated as 100 multiplied by (post-Baseline visit value minus Baseline divided by Baseline).
Percent Change From Baseline in Urine Concentration of Calcium, Creatinine Concentration, Magnesium, Phosphate, Protein During Combination Treatment Period
Time frame: Baseline (Day 1), Weeks 1, 3, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 48, 56 and 64
Urine samples were collected to analyze the urinalysis parameters: Calcium, Creatinine concentration (conc), Magnesium, Phosphate and Protein. Baseline value is the latest GSK2636771 pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Percent change from Baseline was calculated as 100 multiplied by (post-Baseline visit value minus Baseline divided by Baseline).
Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings During Combination Treatment Period
Time frame: Weeks 4, 8, 16, 24, 32, 40, 48, 56, 64, 72, 80 and 88
A 12-lead ECG was obtained after the participant had rested at least 5 minutes in a semi-recumbent or supine position at each time point during the study using ECG machine that automatically measured PR, QRS, QT and Corrected QT interval (QT duration corrected for heart rate by Bazett's formula [QTcB] and Fridericia's formula [QTcF]). Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Number of participants with abnormal clinical significant ECG findings are presented.
Number of Participants With Worst Case Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Results by Maximum Grade Increase Post-Baseline Relative to Baseline During Combination Treatment Period
Time frame: Up to maximum 654 days
SBP and DBP were measured after resting for 5 minutes in semi-supine position. SBP and DBP were graded according to Common Toxicity Criteria for Adverse Events (CTCAE) version 4. 'Any grade increase' is defined as an increase in CTCAE grade relative to Baseline grade. For SBP, Grade 0: <120 millimeters of mercury [mmHg]), Grade 1: 120-139 mmHg, Grade 2: 140-159 mmHg, Grade 3:>=160 mmHg. For DBP, Grade 0: <80 mmHg, Grade 1: 80-89 mmHg, Grade 2: 90-99 mmHg, Grade 3: >=100 mmHg. Higher grade indicate worst outcome. Data for worst-case post-Baseline is reported.
Number of Participants With Worst Case Post-Baseline Results for Heart Rate During Combination Treatment Period
Time frame: Up to maximum 654 days
Heart rate was measured after resting for 5 minutes in semi-supine position. The clinical concern range for heart rate was: low: decrease to <60 beats per minute (bpm) and high: increase to >100 bpm. Participants were counted in the worst case category that their value changed to (low, within range or no change, or high) unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the 'Change to normal or No Change' category. Participants were counted twice if the participant had both values 'decrease to <60 bpm' and 'increase to >100 bpm' during post-Baseline visits. Data for worst case post-Baseline is reported.
Number of Participants With Worst Case Post-Baseline Results for Body Temperature During Combination Treatment Period
Time frame: Up to maximum 654 days
Temperature was measured after resting for 5 minutes in semi-supine position. The clinical concern range for body temperature was: low: decrease to <=35 degrees celsius, high: increase to >=38 degrees celsius. Participants were counted in the worst case category that their value changed to (low, within range or no change, or high) unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the 'Change to normal or No Change' category. Participants were counted twice if the participant had both values 'decreased to <=35 degree celsius' and 'increased to >=38 degrees celsius' during post-Baseline visits. Data for worst-case post-Baseline is presented.
Non-progressive Disease (Non-PD) Rate at Week 12 According to Prostate Cancer Working Group 2 (PCWG2) Criteria in GSK2636771 200mg/Enzalutamide 160mg - Overall Arm
Time frame: At Week 12
The 12-week non-PD rate was defined as percentage of participants without progression(non-PD) at Week12 as determined from Prostate-specific antigen(PSA) results, radiographic assessment per Response Evaluation Criteria In Solid Tumors(RECIST)1.1 and bone scan.Disease progression was defined by 1 or more of the following:PSA progression alone; PSA progression according to the PCWG2 criteria with accompanying progression by RECIST1.1 or bone scan for participants with soft tissue Baseline disease; Bone progression on bone scan according to PCWG2 criteria; or Radiographic progression in soft tissue or bone by RECIST1.1 for participants with Baseline disease.Modified All Treated Clinical Activity Population consisted of all participants who received at least 1 dose of GSK2636771 and who were treated at the same dose as dose expansion cohort and have been on study drug for at least 12weeks or have discontinued study treatment due to disease progression, died or withdrawn for any reason.

11 secondary outcomes

Prostate-specific Antigen Decrease From Baseline >=50% (PSA50) Response Rate at 12 Weeks During Combination Treatment Period
Time frame: At Week 12
Objective Response Rate (ORR) During Combination Treatment Period
Time frame: Up to maximum 654 days
Time to PSA Progression According to PCWG2 Criteria During Combination Treatment Period
Time frame: Up to maximum 654 days
Time to Radiological Progression According to PCWG2 Criteria During Combination Treatment Period
Time frame: Up to maximum 654 days
Radiological Progression Free Survival (rPFS) Per PCWG2 Criteria During Combination Treatment Period
Time frame: Up to maximum 654 days
Plasma Concentration of GSK2636771 in GSK2636771/Enzalutamide Expansion Cohort in Combination Treatment Period
Time frame: Week 5: Pre-dose, 1, 2, 3, 5-6, 6-7, 7-8 hours post-dose; Weeks 8 and 12: Pre-dose
Plasma Concentration of GSK2636771 in GSK2636771/Enzalutamide Escalation Cohorts in Combination Treatment Period
Time frame: Week 5: Pre-dose, 0.5, 1, 2, 3, 4, 6 hours post-dose; Weeks 8 and 12: Pre-dose
Plasma Concentration of Enzalutamide in GSK2636771/Enzalutamide Escalation Cohorts in Combination Treatment Period
Time frame: Week 5: Pre-dose, 0.5, 1, 2, 3, 4, 6 hours post-dose; Weeks 8 and 12: Pre-dose
Plasma Concentration of Enzalutamide in GSK2636771/Enzalutamide Expansion Cohort in Combination Treatment Period
Time frame: Week 5: Pre-dose, 1, 2, 3, 5-6, 6-7, 7-8 hours post-dose; Weeks 8 and 12: Pre-dose
Plasma Concentration of N-desmethyl Enzalutamide in GSK2636771/Enzalutamide Escalation Cohorts in Combination Treatment Period
Time frame: Week 5: Pre-dose, 0.5, 1, 2, 3, 4, 6 hours post-dose; Weeks 8 and 12: Pre-dose
Plasma Concentration of N-desmethyl Enzalutamide in GSK2636771/Enzalutamide Expansion Cohort in Combination Treatment Period
Time frame: Week 5: Pre-dose, 1, 2, 3, 5-6, 6-7, 7-8 hours post-dose; Weeks 8 and 12: Pre-dose

Results and safety

Results posted to the registry on 22 Oct 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Enzalutamide Only (run-in Period)	37	36
GSK2636771 200mg/Enzalutamide 160mg Escalation	0	0
GSK2636771 200mg/Enzalutamide 160mg Expansion	0	0
GSK2636771 300mg/Enzalutamide 160mg Escalation	0	0
GSK2636771 400mg/Enzalutamide 160mg Escalation	0	0

Primary outcome: Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs) During run-in Period

Time frame: Up to Week 2. Count of participants. Unit: Participants

Measure	Enzalutamide Only (run-in Period) n = 37
Non-SAEs	11
SAEs	1

Population analysed: All Treated Safety Population consisted of all participants who received at least one dose of Enzalutamide.

Primary outcome: Number of Participants With Non-SAEs and SAEs During Combination Treatment Period

Time frame: Up to maximum 675 days. Count of participants. Unit: Participants

Measure	GSK2636771 200mg/Enzalutamide 160mg Escalation n = 11	GSK2636771 200mg/Enzalutamide 160mg Expansion n = 11	GSK2636771 300mg/Enzalutamide 160mg Escalation n = 12	GSK2636771 400mg/Enzalutamide 160mg Escalation n = 2
Non-SAEs	11	11	12	2
SAEs	2	2	2	0

Population analysed: All Treated Safety Population consisted of all participants who received at least one dose of GSK2636771 or Enzalutamide. Only those participants with data available at the indicated time points were analyzed.

Primary outcome: Number of Participant With Dose-limiting Toxicities (DLT) During Combination Treatment Period

Time frame: Up to Day 28. Count of participants. Unit: Participants

Measure	GSK2636771 200mg/Enzalutamide 160mg Escalation n = 11	GSK2636771 200mg/Enzalutamide 160mg Expansion n = 11	GSK2636771 300mg/Enzalutamide 160mg Escalation n = 12	GSK2636771 400mg/Enzalutamide 160mg Escalation n = 2
Value	1	0	2	2

Population analysed: All Treated Safety Population. Only those participants with data available at the indicated time points were analyzed.

Primary outcome: Percent Change From Baseline in Hematology Parameters During Combination Treatment Period: Basophils, Eosinophils, Hematocrit, Hemoglobin, Lymphocytes, MCH, MCV, Monocytes, Total Neutrophils, Platelet Count, WBC Count

Time frame: Baseline (Day 1), Weeks 2,3,4,5,8,12,16,20,24,28,32,36,40,44,48,52,56,60,64,68,72,76,80,84 and 88. Mean (Standard Deviation). Unit: Percent change

Measure	GSK2636771 200mg/Enzalutamide 160mg Escalation n = 11	GSK2636771 200mg/Enzalutamide 160mg Expansion n = 11	GSK2636771 300mg/Enzalutamide 160mg Escalation n = 12	GSK2636771 400mg/Enzalutamide 160mg Escalation n = 2
Basophils, Week 2, n=5,4,5,1	20.000 (103.6822)	0.000 (0.0000)	30.000 (48.0885)	33.330 (NA)
Basophils, Week 3, n=5,5,6,1	0.000 (70.7107)	27.500 (43.6606)	-16.270 (38.4859)	0.000 (NA)
Basophils, Week 4, n=5,4,5,1	-16.666 (79.9314)	25.000 (50.0000)	26.666 (43.4612)	33.330 (NA)
Basophils, Week 5, n=4,4,5,0	-37.500 (94.6485)	25.000 (50.0000)	27.380 (46.9143)	–
Basophils, Week 8, n=4,4,4,0	-12.500 (25.0000)	25.000 (50.0000)	139.583 (188.2399)	–
Basophils, Week 12, n=3,4,3,0	0.000 (100.0000)	25.000 (50.0000)	51.190 (42.3084)	–
Basophils, Week 16, n=3,4,1,0	-33.333 (57.7350)	16.668 (33.3350)	0.000 (NA)	–
Basophils, Week 20, n=2,3,1,0	-50.000 (70.7107)	0.000 (0.0000)	50.000 (NA)	–

Population analysed: All Treated Safety Population. Only those participants with data available at the indicated time points were analyzed (represented by n= X in the category titles).

11 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to Week 2 for run-in period and up to maximum of 675 days for combination treatment period. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Enzalutamide Only (run-in Period)	1 of 37 (2.7%)	11 of 37 (29.7%)	0 of 37
GSK2636771 200mg/Enzalutamide 160mg Escalation	2 of 11 (18.2%)	11 of 11 (100%)	0 of 11
GSK2636771 200mg/Enzalutamide 160mg Expansion	2 of 11 (18.2%)	11 of 11 (100%)	0 of 11
GSK2636771 300mg/Enzalutamide 160mg Escalation	2 of 12 (16.7%)	12 of 12 (100%)	0 of 12
GSK2636771 400mg/Enzalutamide 160mg Escalation	0 of 2 (0%)	2 of 2 (100%)	0 of 2

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 22 Oct 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 34281912Sarker D, Dawson NA, Aparicio AM, Dorff TB, Pantuck AJ, Vaishampayan UN, Henson L, Vasist L, Roy-Ghanta S, Gorczyca M, York W, Ganji G, Tolson J, de Bono JS. A Phase I, Open-Label, Dose-Finding Study of GSK2636771, a PI3Kbeta Inhibitor, Administered with Enzalutamide in Patients with Metastatic Castration-Resistant Prostate Cancer. Clin Cancer Res. 2021 Oct 1;27(19):5248-5257. doi: 10.1158/1078-0432.CCR-21-1115.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

GSK Clinical Trials study director

GlaxoSmithKline

9 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing GSK2636771 and Enzalutamide in people with Neoplasms, run by GlaxoSmithKline at 9 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in United States, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 Oct 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs) During run-in Period (time frame: Up to Week 2). The study lists 13 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02215096, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Oct 2020; AzTrials last refreshed its copy on 6 Nov 2026.