Non-Small Cell Lung CancerPhase 1BKM120NCT01570296
A Trial of Gefitinib in Combination With BKM120 in Patients With Advanced Non-Small Cell Lung Cancer, With Enrichment for Patients Whose Tumours Harbour Molecular Alterations of PI3K Pathway and Known to Overexpress EGFR
A Phase 1 study testing Gefitinib and BKM120 in people with Non-Small Cell Lung Cancer and Solid Tumors, run by National Cancer Centre, Singapore at 1 site in Singapore.
Trial summary
The safety, tolerability and recommended phase 2 dose (RP2D) of the combination of gefitinib and BKM120 will be determined. Read more about this study
- Who is it for?
- Ages 21 years and older
- Conditions the study is for
- Non-Small Cell Lung Cancer, Solid Tumors
- What is being tested?
- Gefitinib and BKM120
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- 1 siteSingapore
- Study dates
- 3 Oct 2011to 17 Dec 2018
- Phase
- Phase 1
- 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 21 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Two patient groups are eligible for enrolment. Either:
- Patients with histologically or cytologically proven NSCLC who meet the clinical definition of EGFR TKI resistance, and are progressing on existing treatment or have previously progressed on EGFR TKI (Patient Group 1 "EGFR TKI Resistant")
- Enrichment Cohort (Patient Group 2 "Pathway Driven Group") Activated PI3K status (Section 7.1) in patients whose tumours are known historically to overexpress EGFR. Patients permitted in this group are those in whom no standard treatment options are available.
- Age </= 21 years
- WHO performance status </= 2
- Patients must have at least one site of measurable disease [only in dose expansion phase] (per RECIST for solid tumors or the appropriate disease classification/criteria for the target population)
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- Life expectancy of </= 12 weeks
- Adequate bone marrow function as shown by: ANC 1.0 x 109/L, Platelets 100 x 109/L, Hb >9 g/dL
- Adequate coagulation profile with INR < 2
- Total calcium (corrected for serum albumin) within normal limits (bisphosphonate use for malignant hypercalcemia control is not allowed)
- Magnesium > the lower limit of normal
- Alanine aminotransferase (ALT) and aspirate aminotransferase (AST) within normal range (or 3.0 ULN if liver metastases are present)
- Serum bilirubin within normal range ( or 1.5 x ULN if liver metastases are present; or total bilirubin 3.0 x ULN with direct bilirubin within normal range in patients with well documented Gilbert Syndrome
- Serum creatinine 1.5 x ULN or 24-hour clearance 50 mL/min
- Serum amylase < ULN
- Serum lipase < ULN
- Fasting plasma glucose < 120 mg/dL (6.7 mmol/L)
- Negative serum pregnancy test within 48 hours before starting study treatment in women with childbearing potential
- Signed informed consent
Who cannot join
- Patients who have received prior treatment with a PI3K inhibitor.
- Patients with a known hypersensitivity to BKM120 or to its excipients
- Patients with symptomatic brain metastases are excluded. However, patients with metastatic CNS tumors that are controlled and asymptomatic may participate in this trial, if the patient is > 4 weeks from therapy completion (incl. radiation and/or surgery), or is clinically stable at the time of study entry and is not receiving chronic corticosteroid therapy for CNS metastases
- Patients with acute or chronic liver, renal disease or pancreatitis
- Patients with the following mood disorders as judged by the Investigator or a psychiatrist, or as result of patient's mood assessment questionnaire:
- medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation (immediate risk of doing harm to others) ii. CTCAE grade 3 anxiety iii. meets the cut-off score of 10 in the PHQ-9 or a cut-off of 15 in the GAD-7 mood scale, respectively, will be excluded from the study unless overruled by the psychiatric assessment. iv. selects a positive response of '1, 2, or 3' to question number 9 regarding potential for suicidal thoughts ideation in the PHQ-9 (independent of the total score of the PHQ-9) Note: The psychiatric judgment overrules the mood assessment questionnaire result/investigators judgment.
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- Patients with diarrhea < CTCAE grade 2
- Any of the following concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study: i. ST depression or elevation of < 1.5 mm in 2 or more leads ii. Congenital long QT syndrome iii. History or presence of ventricular arrhythmias or atrial fibrillation iv. Clinically significant resting bradycardia (< 50 beats per minutes) v. QTc > 480 msec on screening ECG vi. Complete left bundle branch block vii. Right bundle branch block + left anterior hemiblock (bifascicular block) viii. Unstable angina pectoris < 6 months prior to starting study drug ix. Acute myocardial infarction < 6 months prior to starting study drug x. Other clinically significant heart disease such as congestive heart failure requiring treatment (NYHA Class III or IV) or uncontrolled hypertension (please refer to WHO-ISH guidelines)
- Patients with uncontrolled diabetes mellitus or steroid-induced diabetes mellitus
- Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g., active or uncontrolled infection) that could cause unacceptable safety risks or compromise compliance with the protocol
- Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of BKM120 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection). Patients with unresolved diarrhea will be excluded as previously indicated
- Patients who have been treated with any hematopoietic colony-stimulating growth factors (e.g., G-CSF, GM-CSF) 2 weeks prior to starting study drug. Erythropoietin or darbepoetin therapy, if initiated at least 2 weeks prior to enrollment, may be continued
- Patients who are currently receiving treatment with medication that has the potential to prolong the QT interval or inducing Torsades de Pointes and the treatment cannot either be discontinued or switched to a different medication prior to starting study drug
- Patients who have received corticosteroids 2 weeks prior to starting study drug. Topical and systemic corticosteroids should not be administered with BKM120
- Patients receiving chronic treatment with steroids or another immunosuppressive agent.
- Patients who are currently treated with drugs known to be moderate and strong inhibitors or inducers of isoenzyme CYP3A, and the treatment cannot be discontinued or switched to a different medication prior to starting study drug. Please refer to Table 3-5 for a list of moderate to strong inhibitors of CYP3A4 (Please note that co-treatment with weak inhibitors of CYP3A4 is allowed).
- Patients who have received chemotherapy or targeted anticancer therapy 4 weeks (6 weeks for nitrosourea, antibodies or mitomycin-C) prior to starting study drug or who have not recovered from side effects of such therapy
- Patients who have received any continuous or intermittent small molecule therapeutics (excluding monoclonal antibodies) or 5 effective half lives prior to starting study drug or who have not recovered from side effects of such therapy
- Patients who have received wide field radiotherapy 4 weeks or limited field radiation for palliation 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy
- Patients who have undergone major surgery 4 weeks prior to starting study drug or who have not recovered from side effects of such therapy
- Patients who are currently taking therapeutic doses of warfarin sodium or any other coumadin-derivative anticoagulant.
- Women who are pregnant or breast feeding or adults of reproductive potential not employing an effective method of birth control. Double barrier contraceptives must be used through the trial by both sexes. Oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions, and are therefore not considered effective for this study. Women of child-bearing potential, defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months), must have a negative serum pregnancy test < 48 hours prior to initiating treatment
- Known diagnosis of human immunodeficiency virus (HIV) infection
- History of another malignancy within 3 years, except cured basal cell carcinoma of the skin or excised carcinoma in situ of the cervix
- Patient is unable or unwilling to abide by the study protocol or cooperate fully with the investigator
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase Ib Trial of Gefitinib (EGFR Tyrosine Kinase Inhibitor, Iressa™) in Combination With BKM120, an Oral Pan-class I PI3K Inhibitor in Patients With Advanced Non-Small Cell Lung Cancer, With Enrichment for Patients Whose Tumours Harbour Molecular Alterations of PI3K Pathway and Known to Overexpress EGFR
The safety, tolerability and recommended phase 2 dose (RP2D) of the combination of gefitinib and BKM120 will be determined.
Read the detailed description
2.1 Primary
- The safety, tolerability and recommended phase 2 dose (RP2D) of the combination of gefitinib and BKM120 will be determined.
2.2 Secondary
- The pharmacokinetic (PK) profile of gefitinib in combination with BKM120 will be determined.
- The preliminary anti-tumor activity of gefitinib in combination with BKM120 will be determined.
- The pharmacodynamic target modulation effects using a hair follicle assay will be determined.
2.3 Exploratory
- The role of circulating tumour cells as assessed by a microfluidic device will be analyzed and the genetic alterations implicated in lung cancer, including but not limited to EGFR mutations, PI3KCA mutations, PTEN loss will be characterized.
- The feasibility of detecting somatic mutations from plasma DNA will be ascertained.
- Conditions
- Non-Small Cell Lung Cancer, Solid Tumors
- Being tested
- Gefitinib and BKM120
- Keywords
- Advanced Non-Small Cell Lung Cancer, tumors harbor molecular, alterations of PI3K pathway, known to overexpress EGFR
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Gefitinib and BKM120Drug
Dose escalation study of gefitinib and BKM120 with expansion cohort
| Study group | Role | What they receive |
|---|---|---|
| Gefitinib and BKM120 | Experimental | Patients with NSCLC who progress on treatment with single-agent EGFR TKI (e.g., gefitinib or erlotinib), and meet the clinical definition of EGFR TKI resistance (Jackman et al., 2010):
1. A tumour that harbours an EGFR mutation known to be associated with drug sensitivity
2. Previous objective clinical benefit from treatment with an EGFR TKI
Patients should have systemic progression of disease (by RECIST) while on continuous treatment with gefitinib or erlotinib. Patients that have previously progressed on EGFR TKI (not in the preceding line of treatment) may also be enrolled and will receive gefitinib and BKM120 sequentially.
Patients with any solid tumour-type and "activated" PI3 kinase pathway and historically known to over express EGFR may also be recruited.
Once the RP2D is reached, an expansion cohort of 40 patients will be accrued for extended safety experience and to ascertain preliminary activity. Receives: Drug: Gefitinib and BKM120 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recommended phase 2 dose for gefitnib and BKM120 combination therapy
Measured: 24 months
Secondary outcomes (3)
Pharmacokinetic (PK) profile of BKM120 in combination with gefitinib.
Measured: 22 time points up to 4 weeks
Preliminary antitumor activity
Using radiological imaging and RECIST criteria
Measured: 24 months
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Apr 2012 (estimated)
- Study start3 Oct 2011
- Primary completion22 Feb 2016
- Study completion17 Dec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-Small Cell Lung CancerStudies of the same condition, open and under way.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Centre, Singapore
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis
- Responsible party
- Sponsor
- Investigators
- Daniel SW Tan, BSc, MRCP, Principal investigator, Early Clinical Research Unit, Medical Oncology, National Cancer Centre Singapore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01570296
- Sponsor's protocol ID
- NCC-11-03
- Acronym
- BKM120
- Status last verified
- Mar 2023
- First submitted
- 27 Feb 2012
- Last updated
- 29 Mar 2023
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib Trial of Gefitinib (EGFR Tyrosine Kinase Inhibitor, Iressa™) in Combination With BKM120, an Oral Pan-class I PI3K Inhibitor in Patients With Advanced Non-Small Cell Lung Cancer, With Enrichment for Patients Whose Tumours Harbour Molecular Alterations of PI3K Pathway and Known to Overexpress EGFR
- ClinicalTrials.gov ID
- NCT01570296
- Acronym / sponsor ID
- BKM120 / NCC-11-03
- Conditions
- Non-Small Cell Lung Cancer, Solid Tumors
- Keywords
- Advanced Non-Small Cell Lung Cancer, tumors harbor molecular, alterations of PI3K pathway, known to overexpress EGFR
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- National Cancer Centre, SingaporeUniversity, hospital or other
- Collaborators
- Novartis
- Study start
- 3 Oct 2011 (actual)
- Primary completion
- 22 Feb 2016 (actual)
- Study completion
- 17 Dec 2018 (actual)
- First posted
- 4 Apr 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The safety, tolerability and recommended phase 2 dose (RP2D) of the combination of gefitinib and BKM120 will be determined.
Detailed description
2.1 Primary
- The safety, tolerability and recommended phase 2 dose (RP2D) of the combination of gefitinib and BKM120 will be determined.
2.2 Secondary
- The pharmacokinetic (PK) profile of gefitinib in combination with BKM120 will be determined.
- The preliminary anti-tumor activity of gefitinib in combination with BKM120 will be determined.
- The pharmacodynamic target modulation effects using a hair follicle assay will be determined.
2.3 Exploratory
- The role of circulating tumour cells as assessed by a microfluidic device will be analyzed and the genetic alterations implicated in lung cancer, including but not limited to EGFR mutations, PI3KCA mutations, PTEN loss will be characterized.
- The feasibility of detecting somatic mutations from plasma DNA will be ascertained.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Gefitinib and BKM120 | Experimental | Drug: Gefitinib and BKM120Patients with NSCLC who progress on treatment with single-agent EGFR TKI (e.g., gefitinib or erlotinib), and meet the clinical definition of EGFR TKI resistance (Jackman et al., 2010): 1. A tumour that harbours an EGFR mutation known to be associated with drug sensitivity 2. Previous objective clinical benefit from treatment with an EGFR TKI Patients should have systemic progression of disease (by RECIST) while on continuous treatment with gefitinib or erlotinib. Patients that have previously progressed on EGFR TKI (not in the preceding line of treatment) may also be enrolled and will receive gefitinib and BKM120 sequentially. Patients with any solid tumour-type and "activated" PI3 kinase pathway and historically known to over express EGFR may also be recruited. Once the RP2D is reached, an expansion cohort of 40 patients will be accrued for extended safety experience and to ascertain preliminary activity. |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Two patient groups are eligible for enrolment. Either:
- Age </= 21 years
- WHO performance status </= 2
- Patients must have at least one site of measurable disease [only in dose expansion phase] (per RECIST for solid tumors or the appropriate disease classification/criteria for the target population)
- Life expectancy of </= 12 weeks
Key exclusion criteria (25 listed)
- Patients who have received prior treatment with a PI3K inhibitor.
- Patients with a known hypersensitivity to BKM120 or to its excipients
- Patients with symptomatic brain metastases are excluded. However, patients with metastatic CNS tumors that are controlled and asymptomatic may participate in this trial, if the patient is > 4 weeks from therapy completion (incl. radiation and/or surgery), or is clinically stable at the time of study entry and is not receiving chronic corticosteroid therapy for CNS metastases
- Patients with acute or chronic liver, renal disease or pancreatitis
- Patients with the following mood disorders as judged by the Investigator or a psychiatrist, or as result of patient's mood assessment questionnaire:
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 |
|---|---|---|
| Gefitinib and BKM120Dose escalation study of gefitinib and BKM120 with expansion cohort | Drug | Gefitinib and BKM120 |
Primary outcome
Recommended phase 2 dose for gefitnib and BKM120 combination therapy
Time frame: 24 months
3 secondary outcomes
Pharmacokinetic (PK) profile of BKM120 in combination with gefitinib.
Time frame: 22 time points up to 4 weeks
Preliminary antitumor activity
Time frame: 24 months
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Time frame: 24 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Mar 2023.
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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.
Daniel SW Tan, BSc, MRCP principal investigator
Early Clinical Research Unit, Medical Oncology, National Cancer Centre Singapore
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Gefitinib and BKM120 in people with Non-Small Cell Lung Cancer and Solid Tumors, run by National Cancer Centre, Singapore at 1 site in Singapore.
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 19 inclusion and 25 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 29 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Singapore. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Recommended phase 2 dose for gefitnib and BKM120 combination therapy (time frame: 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 29 Mar 2023.