AzTrials
AzTrials

Solid TumoursPhase 2NCT03266159

A Dose Escalation Study to Investigate the Safety, Pharmacokinetics (PK), Pharmacodynamics (PD), and Clinical Activity of GSK525762 Plus Trametinib in Subjects With Solid Tumors

A Phase 2 study testing GSK525762 Besylate tablets and Trametinib tablets in people with Solid Tumours, run by GlaxoSmithKline.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

GSK525762 is a novel inhibitor of bromodomain and extraterminal (BET) proteins. Trametinib is a potent inhibitor of the mitogen-activated protein kinase proteins (MEK1 and MEK2). GSK525762 and trametinib are critical for growth and survival of tumor cells. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Solid Tumours
What is being tested?
GSK525762 Besylate tablets and Trametinib tablets
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
27 Nov 2017to 19 Aug 2020
Phase
Phase 2
Are there results?
None posted in the registry

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
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Written informed consent provided.
  • Males and females 18 years old and greater, at the time of signing the informed consent.
  • Histologically- or cytologically confirmed diagnosis of one of the following; Part 1 dose escalation cohorts: Advanced (metastatic or non-resectable) SCLC with any mutational status, or any solid malignancy that demonstrates an activating mutation in Harvey rat sarcoma viral oncogene homolog (HRAS), Kirsten rat sarcoma viral oncogene homolog (KRAS), or neuroblastoma RAS viral (v-ras) oncogene homolog (NRAS); Part 1 dose expansion (PD cohort[s]) and part 2: Advanced (metastatic or non-resectable) SCLC with any mutational status, or adenocarcinoma of the colon or rectum, or NSCLC or adenocarcinoma of the pancreas, all of which must demonstrate an activating mutation in HRAS, KRAS, or NRAS; Part 2 "basket" cohort: Advanced (metastatic or non-resectable) solid malignancy that demonstrates Ras pathway activation (including but not limited to activating BRAF/HRAS/KRAS/NRAS mutation, inactivating neurofibromin (NF1) mutation, or evidence of Ras pathway activation by gene expression analysis).
  • Disease that did not respond to, or progressed after, at least 1 prior line of therapy, or has no generally-accepted standard therapy (dose escalation cohorts and optional "basket" cohort only).
  • Measurable disease during part 1, measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 is recommended but not required. Subjects enrolled in part 2 must demonstrate measurable disease per RECIST v1.1.
  • PD expansion subjects only: Subjects must consent to pre-dosing and on-therapy tumor biopsies and additional sample collection procedures.
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  • All prior treatment-related toxicities must be National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v4 <=Grade 1 (except alopecia [permitted at any grade]) and peripheral neuropathy (permitted at <=Grade 2) at the time of screening.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1.
  • Must have adequate organ function as defined by the following values: Absolute neutrophil count (ANC) >=1.5 x 10^9/liter (L); hemoglobin >=9 grams per deciliter (g/dL) subjects that required transfusion or growth factor need to demonstrate stable hemoglobin for 7 days of 9 g/dL; platelets >=100 x 10^9/L; prothrombin time (PT)/International normalized ration (INR) and partial thromboplastin time (PTT) <=1.5 x upper limit of normal (ULN); albumin >=2.5 g/dL; total bilirubin <=1.5 x ULN; aspartate transaminase (AST) <=2.5 x ULN; alanine transaminase (ALT) <=2.5 x ULN OR <5 x ULN; estimated glomerular filtration rate >=50 milliliter (mL)/minute/1.73 m^2; ejection fraction>= lower limit of normal (LLN); troponin <=ULN
  • Able to swallow and retain orally administered medication.
  • A female subject is eligible to participate if she is of: Non-childbearing potential; Childbearing potential and agrees to use one of the contraception methods from the time of the screening pregnancy test until at least 7 months after the last dose of study treatment; All female subjects of childbearing potential must have a negative serum pregnancy test <=7 days prior to first dose of study treatment; Female subjects who are lactating must discontinue nursing prior to the first dose of study treatment and must refrain from nursing throughout the treatment period and for 5 half-lives of GSK525762/trametinib or at least 28 days (whichever is longer) following the last dose of study treatment.
  • Male subjects with female partners of childbearing potential must agree to abide by the reproductive guidelines from the first dose of study treatment and for at least 16 weeks after the last dose of study treatment.

Who cannot join

  • Primary malignancy of the central nervous system or malignancies related to human immunodeficiency virus (HIV) or solid organ transplant.
  • Prior therapy with any BET inhibitor.
  • Recent prior therapy, defined as follows: Any non-biologic anti-cancer drug (either investigational or approved) within 14 days or 5 half-lives, whichever is longer, prior to the first dose of GSK525762 and trametinib; any nitrosoureas or mitomycin C within 42 days prior to the first dose of GSK525762 and trametinib; any biologic anti-cancer agent within 28 days prior to the first dose of GSK525762 and trametinib; any radiotherapy within 14 days or major surgery within 28 days prior to the first dose of GSK525762 and trametinib.
  • Therapeutic-dose anticoagulation (e.g., warfarin, heparin) must be discontinued and coagulation parameters must be normalized prior to the first dose of GSK525762 and trametinib. Low dose (prophylactic) low molecular weight heparin or other anticoagulants are permitted.
  • Current or planned use of a prohibited medication during treatment with GSK525762 and trametinib.
  • Evidence of severe or uncontrolled systemic diseases (e.g., unstable or uncompensated respiratory, hepatic, renal, cardiac disease, or clinically significant bleeding episodes). Any serious and/or unstable pre-existing medical (aside from malignancy) condition, psychiatric disorder, or other conditions that could interfere with subject's safety, obtaining informed consent or compliance to the study procedures, in the opinion of the investigator.
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  • Symptomatic or untreated leptomeningeal or brain metastases or spinal cord compression. Subjects with a history of central nervous system (CNS) involvement may be enrolled so long as all of the following requirements are met: Subjects must have received definitive therapy for the CNS involvement (e.g., surgery, radiotherapy, or stereotactic radiosurgery [i.e., gamma knife or equivalent]); At least 28 days must have elapsed since the CNS-directed therapy; All symptoms and AEs from the CNS-directed therapy must have resolved to <=Grade 1; Lesion stability must be demonstrated by serial imaging spaced at least 28 days apart; If the subject remains on corticosteroids, the dose must be stable to decreasing for the 28-day interval prior to study Day 1; The subject does not receive any enzyme-inducing anticonvulsants (EIACs) from 14 days prior to study Day 1 until the End of Treatment.
  • Cardiac abnormalities as evidenced by any of the following: Baseline QTcF interval >450 millisecond (msec); Clinically significant conduction abnormalities or arrhythmias; Presence of cardiac pacemaker or defibrillator with a paced ventricular rhythm limiting ECG analysis; History or evidence of current >=Class II congestive heart failure as defined by New York Heart Association (NYHA); History of acute coronary syndromes (including unstable angina and myocardial infarction), coronary angioplasty, or stenting within the past 3 months. Subjects with a history of stent placement requiring ongoing antithrombotic therapy (e.g., clopidogrel, prasugrel) will not be permitted to enroll.
  • Current active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones, liver metastases, or otherwise stable chronic liver disease per investigator assessment).
  • Presence of hepatitis B surface antigen (HBsAg) or positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment.
  • History of known HIV infection or positive HIV test at screening.
  • Any serious known immediate or delayed hypersensitivity reaction(s) to GSK525762 or trametinib, or idiosyncrasy to drugs chemically related to the investigational drugs.
  • Subjects with a history of known bleeding disorder(s) or history of clinically significant (as judged by the investigator and medical monitor) hemorrhage (e.g., GI, neurologic, pulmonary) within the past 6 months.
  • History of retinal vein occlusion.
  • History of pneumonitis or interstitial lung disease.
  • Any clinically significant gastrointestinal abnormalities that may alter absorption of oral medications, (e.g., malabsorption syndrome).

About this study

Official title: A Phase I/II Open-Label, Dose Escalation Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of GSK525762 Plus Trametinib in Subjects With Small Cell Lung Cancer and Ras-Mutated Solid Tumors

GSK525762 is a novel inhibitor of bromodomain and extraterminal (BET) proteins. Trametinib is a potent inhibitor of the mitogen-activated protein kinase proteins (MEK1 and MEK2). GSK525762 and trametinib are critical for growth and survival of tumor cells. This will be the first study demonstrating the synergistic effect of BET inhibitor and MEK inhibitor administered together against tumor cell growth. This study aims to evaluate the safety, tolerability, PK, PD, and preliminary efficacy of combination of GSK525762 and trametinib when administered concomitantly to subjects with small cell lung cancer (SCLC) and rat sarcoma virus oncogene homolog (Ras) mutated solid tumors. The study will be conducted in two parts; part 1 will consists of dose escalation and dose expansion cohorts and part 2 will consists of four disease specific cohorts (SCLC, Ras-mutated adenocarcinoma [RMAC] of the colon [Ras-mutated colorectal cancer {RMCRC}] and/or rectum, Ras-mutated non small cell lung cancer [RMNSCLC], Ras-mutated pancreatic adenocarcinoma [RMPAC]) and an optional "basket" cohort (Ras-pathway activated solid tumors [RAST]). Part 1 will focus on selection of the Part 2 dose based on safety/tolerability, PK, PD, and efficacy. Part 2 will investigate the overall response rate and clinical response. The total duration of study will be approximately three years (nine to twelve months for part 1 and two years for part 2). Approximately 138-156 subjects will be enrolled in the study.

Conditions
Solid Tumours
Being tested
GSK525762 Besylate tablets, Trametinib tablets
Keywords
Dose escalation, Small cell lung cancer, Trametinib, GSK525762, Ras-mutations, BET inhibitor
Medical subject headings
Small Cell Lung Carcinoma

What participants receive

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

  • GSK525762 Besylate tabletsDrug

    GSK525762 Besylate film coated tablets will be available as a 20 mg tablet strength, yellowish pink in color, round and biconvex with no markings. It will be administered with 240mL of liquid.

  • Trametinib tabletsDrug

    Trametinib film coated tablets will be available as 0.5 mg and 2 mg dose strengths. Trametinib 0.5 mg will be yellow colored, modified oval, biconvex, tablets with 'GS' debossed on one face and 'TFC' on the opposing face.

    Trametinib 2 mg will be pink colored, round, biconvex tablets with 'GS' debossed on one face and 'HMJ' on the opposing face. Doses will be taken at least 1 hour before or at least 2 hours after a meal.

Study groups in NCT03266159
Study groupRoleWhat they receive
Part 1: Subjects receiving GSK525762 + trametinibExperimentalEligible subjects will receive doses of GSK525762 with a starting dose of 40 milligrams (mg), or 60 mg in combination with trametinib with a starting dose of 1 mg or 1.5 mg or 2 mg, administered orally once daily. Dose escalation will continue until the maximally-tolerated dose combination (MTC) is reached. Once the MTC is reached, subjects will be enrolled in expansion cohort and will receive a fixed dose combination.
Receives: Drug: GSK525762 Besylate tablets; Drug: Trametinib tablets
Part 2: Subjects with SCLC receiving GSK525762+ trametinibExperimentalEligible subjects with small cell lung cancer (SCLC) will receive their Part 2 dose as the dose combination of GSK525762 with trametinib selected at the end of Part 1.
Receives: Drug: GSK525762 Besylate tablets; Drug: Trametinib tablets
Part 2: Subjects with RMCRC receiving GSK525762+ trametiniExperimentalEligible subjects with Ras-mutated colorectal cancer (RMCRC) will receive their Part 2 dose as the dose combination of GSK525762 with trametinib selected at the end of Part 1.
Receives: Drug: GSK525762 Besylate tablets; Drug: Trametinib tablets
Part 2: Subjects with RMNSCLC receiving GSK525762+ trametinibExperimentalEligible subjects with Ras-mutated non small cell lung cancer (RMNSCLC) will receive their Part 2 dose as the dose combination of GSK525762 with trametinib selected at the end of Part 1.
Receives: Drug: GSK525762 Besylate tablets; Drug: Trametinib tablets
Part 2: Subjects with RMPAC receiving GSK525762+ trametinibExperimentalEligible subjects with Ras-mutated pancreatic adenocarcinoma (RMPAC) will receive their Part 2 dose as the dose combination of GSK525762 with trametinib selected at the end of Part 1.
Receives: Drug: GSK525762 Besylate tablets; Drug: Trametinib tablets
Part 2: Subjects with RAST receiving GSK525762+ trametinibExperimentalEligible subjects with Ras-pathway activated solid tumors (RAST) will receive their Part 2 dose as the dose combination of GSK525762 with trametinib selected at the end of Part 1.
Receives: Drug: GSK525762 Besylate tablets; Drug: Trametinib tablets

What is being measured

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

  1. Part 1: Number of subjects with adverse events (AEs) and serious adverse events (SAEs)

    An AE is any untoward medical occurrence in a subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgement will be categorized as SAE.

    Measured: Up to 12 months

  2. Part 1: Number of subjects with dose limiting toxicities (DLT) as a measure of safety

    DLT is defined by the occurrence of severe toxicities during the first cycle of cancer therapy. An event will be considered a DLT if it occurs within the first 21 days of treatment and meets the DLT criteria.

    Measured: Up to 12 months

  3. Part 1: Area under the plasma concentration time curve from time 0 to last time of quantifiable concentration (AUC [0-T]) of GSK525762 and trametinib

    Blood samples will be collected at the indicated time points for pharmacokinetic analysis and concentration of GSK525762 and trametinib will be determined in plasma.

    Measured: Pre-dose,30minutes ±5minutes,1 hour±5minutes,2hours±10 minutes,3hours±10minutes, 4hours±15minutes,6±1hour,8±1hour, and 24±2hours at Day1 Week1;Day1 Week3. Pre-dose;1hour±10minutes post-dose at Day1 Week2,Day1 Week 4;every 8 Weeks from Week8 to Week52

  4. Part 1: Pre-dose (trough) concentration at the end of a dosing interval (Ctau) of GSK525762 and trametinib

    Blood samples will be collected at the indicated time points for pharmacokinetic analysis and concentration of GSK525762 and trametinib will be determined in plasma.

    Measured: Pre-dose,30minutes ±5minutes,1 hour±5minutes,2hours±10 minutes,3hours±10minutes, 4hours±15minutes,6±1hour,8±1hour, and 24±2hours at Day1 Week1;Day1 Week3. Pre-dose;1hour±10minutes post-dose at Day1 Week2,Day1 Week 4;every 8 Weeks from Week8 to Week52

  5. Part 1: Maximum observed plasma concentration (Cmax) of GSK525762 and trametinib

    Blood samples will be collected at the indicated time points for pharmacokinetic analysis and concentration of GSK525762 and trametinib will be determined in plasma.

    Measured: Pre-dose,30minutes ±5minutes,1 hour±5minutes,2hours±10 minutes,3hours±10minutes, 4hours±15minutes,6±1hour,8±1hour, and 24±2hours at Day1 Week1;Day1 Week3. Pre-dose;1hour±10minutes post-dose at Day1 Week2,Day1 Week 4;every 8 Weeks from Week8 to Week52

  6. Part 1: Time to Cmax (Tmax) of GSK525762 and trametinib

    Blood samples will be collected at the indicated time points for pharmacokinetic analysis and concentration of GSK525762 and trametinib will be determined in plasma.

    Measured: Pre-dose,30minutes ±5minutes,1 hour±5minutes,2hours±10 minutes,3hours±10minutes, 4hours±15minutes,6±1hour,8±1hour, and 24±2hours at Day1 Week1;Day1 Week3. Pre-dose;1hour±10minutes post-dose at Day1 Week2,Day1 Week 4;every 8 Weeks from Week8 to Week52

  7. Part 1: Change from Baseline in the phosphorylation of extracellular signal-regulated kinase (pERK) levels

    The pERK levels will be assessed in pre-therapy and on-therapy tumor samples.

    Measured: Baseline and up to Week 3

  8. Part 1: Change from Baseline circulating protein or ribonucleic acid (RNA) biomarkers

    The circulating protein or RNA biomarkers including to monocyte chemoattractant protein-1 (MCP-1) will be assessed in pre-therapy and on-therapy blood samples.

    Measured: Baseline and up to Week 3

  9. Part 1: Change from Baseline transcriptional levels and mitogen activated protein (MAP) kinase signaling

    The transcriptional levels and MAP kinase signaling will be assessed in pre-therapy and on-therapy tumor and/or blood samples.

    Measured: Baseline and up to Week 3

  10. Part 1: Overall response rate (ORR)

    ORR is defined as the percentage of subjects with a confirmed complete response (CR) or partial response (PR) at any time as per disease-specific criteria.

    Measured: Up to 12 months

  11. Part 1: Disease control rate (DCR)

    DCR is defined as the percentage of subjects with a confirmed CR, PR, or SD at any time as per disease-specific criteria.

    Measured: Up to 12 months

  12. Part 1: Duration of response (DOR)

    The DOR is defined as, in the subset of subjects who show a confirmed CR or PR, the time from first documented evidence of CR or PR until the first documented sign of disease progression or death.

    Measured: Up to 12 months

  13. Part 2: ORR

    ORR is defined as the percentage of subjects with a confirmed CR or PR at any time as per disease-specific criteria.

    Measured: Up to 24 months

  14. Part 2: Clinical response

    Clinical response is defined as confirmed ORR as per standard evaluation criteria. ORR is the percentage of subjects with a confirmed CR or PR at any time as per disease-specific criteria.

    Measured: Up to 24 months

  15. Part 2: Number of subjects with AEs and SAEs

    An AE is any untoward medical occurrence in a subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgement will be categorized as SAE.

    Measured: Up to 24 months

  16. Part 2: Number of subjects with dose reductions or delays as a measure of safety

    Dose reductions or delays will be evaluated until the end of treatment.

    Measured: Up to 24 months

  17. Part 2: Number of subjects withdrawals due to toxicities

    Withdrawals will be collected until the end of treatment.

    Measured: Up to 24 months

  18. Part 2: Number of subjects with abnormal clinical chemistry laboratory tests

    Clinical chemistry parameters will be analyzed as a measure of safety.

    Measured: Up to 24 months

  19. Part 2: Number of subjects with abnormal hematology laboratory tests

    Hematology parameters will be analyzed as a measure of safety.

    Measured: Up to 24 months

  20. Part 2: Number of subjects with abnormal routine urinalysis laboratory tests

    Urinalysis will be carried out as a measure of safety.

    Measured: Up to 24 months

  21. Part 2: Number of subjects with abnormal systolic blood pressure (SBP) and diastolic blood pressure (DBP) as a measure of safety

    Systolic and diastolic blood pressure will be measured in semi-supine position after 5 minutes of rest.

    Measured: Up to 24 months

  22. Part 2: Number of subjects with abnormal pulse rate

    Pulse rate will be measured in a semi-supine position after 5 minutes of rest..

    Measured: Up to 24 months

  23. Part 2: Number of subjects with abnormal respiratory rate

    Respiratory rate will be measured in a semi-supine position after 5 minutes of rest.

    Measured: Up to 24 months

  24. Part 2: Number of subjects with abnormal body temperature

    Body temperature will be measured in a semi-supine position after 5 minutes of rest.

    Measured: Up to 24 months

  25. Part 2: Number of subjects with abnormal electrocardiogram (ECG) findings

    Triplicate 12-lead ECGs will be obtained at each time point using an ECG machine to measure PR, QRS, QT, and Corrected QT interval (QTc).

    Measured: Up to 24 months

  26. Part 2: Number of subjects with cardiotoxicity and gastrointestinal (GI) toxicity

    Echocardiography (ECHO) or multigated acquisition (MUGA) scan will be performed to assess cardiotoxicity and GI effects will be monitored.

    Measured: Up to 24 months

  27. Part 2: AUC [0-T] of GSK525762 and trametinib

    Blood samples will be collected at the indicated time points for pharmacokinetic analysis and concentration of GSK525762 AND TRAMETINIB will be determined in plasma.

    Measured: Pre-dose, and 0.5hour±5 minutes, 1-2 hours, 4-6hours post-dose at Day1 Week 1, Day1 Week3, and every 8 Weeks from Week8 to Week52

  28. Part 2: Ctau of GSK525762 and trametinib

    Blood samples will be collected at the indicated time points for pharmacokinetic analysis and concentration of GSK525762 and trametinib will be determined in plasma.

    Measured: Pre-dose, and 0.5hour±5 minutes, 1-2 hours, 4-6hours post-dose at Day1 Week 1, Day1 Week3, and every 8 Weeks from Week8 to Week52

  29. Part 2: Cmax of GSK525762 and trametinib

    Blood samples will be collected at the indicated time points for pharmacokinetic analysis and concentration of GSK525762 and trametinib will be determined in plasma.

    Measured: Pre-dose, and 0.5hour±5 minutes, 1-2 hours, 4-6hours post-dose at Day1 Week 1, Day1 Week3, and every 8 Weeks from Week8 to Week52

  30. Part 2: Tmax of GSK525762 and trametinib

    Blood samples will be collected at the indicated time points for pharmacokinetic analysis and concentration of GSK525762 and trametinib will be determined in plasma.

    Measured: Pre-dose, and 0.5hour±5 minutes, 1-2 hours, 4-6hours post-dose at Day1 Week 1, Day1 Week3, and every 8 Weeks from Week8 to Week52

  31. Part 2: Change from Baseline in the pERK levels

    The pERK levels will be assessed in pre-therapy and on-therapy tumor samples.

    Measured: Baseline and up to Week 3

  32. Part 2: Change from Baseline circulating protein or RNA biomarkers

    The circulating protein or RNA biomarkers including to MCP-1 will be assessed in pre-therapy and on-therapy blood samples.

    Measured: Baseline and up to Week 3

  33. Part 2: Change from Baseline transcriptional levels and MAP kinase signaling

    The transcriptional levels and MAP kinase signaling will be assessed in pre-therapy and on-therapy tumor and/or blood samples.

    Measured: Baseline and up to Week 3

Secondary outcomes (24)

  1. Part 1: Number of subjects with AEs and SAEs

    An AE is any untoward medical occurrence in a subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgement will be categorized as SAE.

    Measured: Up to 12 months

  2. Part 1: Number of subjects with dose reductions or delays as a measure of safety

    Subjects will be evaluated for dose reductions and delays. An event will be considered a DLT if it occurs within the first 21 days of treatment and meets the DLT criteria.

    Measured: Up to 12 months

  3. Part 1: Number of subject withdrawals due to toxicities

    DLT is defined by the occurrence of severe toxicities during the first cycle of cancer therapy. An event will be considered a DLT if it occurs within the first 21 days of treatment and meets the DLT criteria.

    Measured: Up to 12 months

  4. Part 1: Number of subjects with abnormal clinical chemistry laboratory tests

    Clinical chemistry parameters will be analyzed as a measure of safety.

    Measured: Up to 12 months

  5. Part 1: Number of subjects with abnormal hematology laboratory tests

    Hematology parameters will be analyzed as a measure of safety.

    Measured: Up to 12 months

  6. Part 1: Number of subjects with abnormal routine urinalysis laboratory tests

    Urinalysis will be carried out as a measure of safety.

    Measured: Up to 12 months

  7. Part 1: Number of subjects with abnormal SBP and DBP as a measure of safety

    Systolic and diastolic blood pressure will be measured in semi-supine position after 5 minutes of rest.

    Measured: Up to 12 months

  8. Part 1: Number of subjects with abnormal pulse rate

    Pulse rate will be measured in a semi-supine position after 5 minutes of rest.

    Measured: Up to 12 months

  9. Part 1: Number of subjects with abnormal respiratory rate

    Respiratory rate will be measured in a semi-supine position after 5 minutes of rest.

    Measured: Up to 12 months

  10. Part 1: Number of subjects with abnormal body temperature

    Body temperature will be measured in a semi-supine position after 5 minutes of rest.

    Measured: Up to 12 months

  11. Part 1: Number of subjects with abnormal ECG findings

    Triplicate 12-lead ECGs will be obtained at each time point using an ECG machine to measure PR, QRS, QT, and QTc.

    Measured: Up to 12 months

  12. Part 1: Number of subjects with cardiotoxicity and GI toxicity

    Echocardiography (ECHO) or multigated acquisition (MUGA) scan will be performed to assess cardiotoxicity and GI effects will be monitored.

    Measured: Up to 12 months

  13. Part 1: (AUC [0-T]) of GSK525762 and trametinib

    Blood samples will be collected at the indicated time points for pharmacokinetic analysis and concentration of GSK525762 and trametinib will be determined in plasma.

    Measured: Pre-dose,30minutes ±5minutes,1 hour±5minutes,2hours±10 minutes,3hours±10minutes, 4hours±15minutes,6±1hour,8±1hour, and 24±2hours at Day1 Week1;Day1 Week3. Pre-dose;1hour±10minutes post-dose at Day1 Week2,Day1 Week 4;every 8 Weeks from Week8 to Week52

  14. Part 1: Ctau of GSK525762 and trametinib

    Blood samples will be collected at the indicated time points for pharmacokinetic analysis and concentration of GSK525762 and trametinib will be determined in plasma.

    Measured: Pre-dose,30minutes ±5minutes,1 hour±5minutes,2hours±10 minutes,3hours±10minutes, 4hours±15minutes,6±1hour,8±1hour, and 24±2hours at Day1 Week1;Day1 Week3. Pre-dose;1hour±10minutes post-dose at Day1 Week2,Day1 Week 4;every 8 Weeks from Week8 to Week52

  15. Part 1: Cmax of GSK525762 and trametinib

    Blood samples will be collected at the indicated time points for pharmacokinetic analysis and concentration of GSK525762 and trametinib will be determined in plasma.

    Measured: Pre-dose,30minutes ±5minutes,1 hour±5minutes,2hours±10 minutes,3hours±10minutes, 4hours±15minutes,6±1hour,8±1hour, and 24±2hours at Day1 Week1;Day1 Week3. Pre-dose;1hour±10minutes post-dose at Day1 Week2,Day1 Week 4;every 8 Weeks from Week8 to Week52

  16. Part 1: Tmax of GSK525762 and trametinib

    Blood samples will be collected at the indicated time points for pharmacokinetic analysis and concentration of GSK525762 and trametinib will be determined in plasma.

    Measured: Pre-dose,30minutes ±5minutes,1 hour±5minutes,2hours±10 minutes,3hours±10minutes, 4hours±15minutes,6±1hour,8±1hour, and 24±2hours at Day1 Week1;Day1 Week3. Pre-dose;1hour±10minutes post-dose at Day1 Week2,Day1 Week 4;every 8 Weeks from Week8 to Week52

  17. Part 1: ORR

    ORR is defined as the percentage of subjects with a CR or PR at any time as per disease-specific criteria.

    Measured: Up to 12 months

  18. Part 1: DCR

    DCR is defined as the percentage of subjects with a confirmed CR, PR, or SD at any time as per disease-specific criteria.

    Measured: Up to 12 months

  19. Part 1: DOR

    The DOR is defined as, in the subset of subjects who show a confirmed CR or PR, the time from first documented evidence of CR or PR until the first documented sign of disease progression or death.

    Measured: Up to 12 months

  20. Part 1: Progression-free survival (PFS)

    PFS defined as the time from first dose of study treatment until the disease progression or death due to any cause.

    Measured: Up to 12 months

  21. Part 2: PFS

    PFS defined as the time from first dose of study treatment until the disease progression or death due to any cause.

    Measured: Up to 24 months

  22. Part 2: DOR

    The DOR is defined as, in the subset of subjects who show a confirmed CR or PR, the time from first documented evidence of CR or PR until the first documented sign of disease progression or death.

    Measured: Up to 24 months

  23. Part 2: DCR

    DCR is defined as the percentage of subjects with a confirmed CR, PR, or SD at any time as per disease-specific criteria.

    Measured: Up to 24 months

  24. Part 2 :Concentrations of GSK525762 and its relevant metabolite(s) and trametinib following repeat dose oral administration.

    Plasma samples will be collected at the indicated time points to measure concentrations of GSK525762 and its relevant metabolite(s) and trametinib following repeat dose oral administration.

    Measured: Pre-dose, and 0.5hour±5 minutes, 1-2 hours, 4-6hours post-dose at Day1 Week 1, Day1 Week3, and every 8 Weeks from Week8 to Week52

Timeline

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

  1. First posted30 Aug 2017
  2. Study start27 Nov 2017 (estimated)
  3. Primary completion19 Aug 2020 (estimated)
  4. Study completion19 Aug 2020 (estimated)

Why it stopped: Study withdrawn before active to fully evaluate impact of changing practice in target population.

Resources

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 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Model description
A sequential combined therapy of GSK525762 plus trametinib will be given to the subjects. Subjects will receive escalating doses in part 1 and the dose combination selected at the end of part 1 will be provided in part 2.
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03266159
Sponsor's protocol ID
204673
Status last verified
Dec 2017
First submitted
25 Aug 2017
Last updated
8 Dec 2017
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing GSK525762 Besylate tablets and Trametinib tablets in people with Solid Tumours, run by GlaxoSmithKline.

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 16 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: withdrawn, as of the sponsor's last update on 8 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.

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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

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?

Part 1: Number of subjects with adverse events (AEs) and serious adverse events (SAEs) (time frame: Up to 12 months). The study lists 33 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 NCT03266159.

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 8 Dec 2017.

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