Status and phase
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About
The study consists of a pre-screening period to determine if the subject's tumor has PTEN deficiencies. Subjects then continue into the screening phase for Part 1, 2, or 3, as appropriate. In Part 1, subjects will then receive a single dose of 25 mg. After analysis of 24 hour pharmacokinetic (PK) samples, subjects may receive continuous dosing or receive a single modified dose. In Part 2, subjects will be enrolled and dose escalation will occur in a 3+3 design. Subjects will receive a single dose on Day 1, and then begin continuous daily dosing after collection of a 72-hour PK sample. Additional subjects may be enrolled at lower dose levels for assessment of pharmacodynamic response. In Part 3, up to two tumor-specific expansion cohorts will be enrolled and receive the MTD or BED as defined in Part 2. A minimum of 12 and a maximum of 20 evaluable subjects will be enrolled in each cohort. Interim monitoring for futility will be incorporated after response data from 12 subjects are available. In addition, up to 20 evaluable subjects will be enrolled into Part 3 -Signal-finding Expansion Cohort at the MTD or BED as defined in Part 2. All subjects in all parts/cohorts will receive daily dosing until withdrawal or unacceptable toxicity. All subjects in all parts/cohorts will receive daily dosing until withdrawal or unacceptable toxicity.
Full description
The study consists of a pre-screening period to determine if the subject's tumor has PTEN deficiencies. Subjects then continue into the screening phase for Part 1, 2, or 3, as appropriate. In Part 1, subjects will then receive a single dose of 25 mg. After analysis of 24 hour pharmacokinetic (PK) samples, subjects may receive continuous dosing or receive a single modified dose. In Part 2, subjects will be enrolled and dose escalation will occur in a 3+3 design. Subjects will receive a single dose on Day 1, and then begin continuous daily dosing after collection of a 72-hour PK sample. Additional subjects may be enrolled at lower dose levels for assessment of pharmacodynamic response. In Part 3, up to two tumor-specific expansion cohorts will be enrolled and receive the MTD or BED as defined in Part 2. A minimum of 12 and a maximum of 20 evaluable subjects will be enrolled in each cohort. Interim monitoring for futility will be incorporated after response data from 12 subjects are available. In addition, up to 20 evaluable subjects will be enrolled into Part 3 -Signal-finding Expansion Cohort at the MTD or BED as defined in Part 2. All subjects in all parts/cohorts will receive daily dosing until withdrawal or unacceptable toxicity. All subjects in all parts/cohorts will receive daily dosing until withdrawal or unacceptable toxicity.
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
Pre-screening Parts 1, 2, and 3
Pre-screening Parts 1 and 2 only
Pre-screening Part 3 only
For Signal-finding Expansion Cohort: one of the specified tumor types that is not responsive to standard therapies, or for which there is no approved or curative therapy, or for which subjects have refused standard therapy, including:
Screening Part 3 includes Pre-screening criteria (above) and
Exclusion criteria
Pre-screening Parts 1, 2, and 3
Screening Parts 1, 2 includes Pre-screening criteria (above) and
Subject has had chemotherapy, radiotherapy, immunotherapy, or other anti-cancer therapy including investigational drugs within 14 days prior to the first dose of the investigational drug described in this study. Hormonal (e.g., anti-androgen) therapies for prostate cancer must be stopped 4 to 6 weeks prior to enrolment. NOTE: Subjects with prostate cancer may remain on LHRH agonists. Subjects with prostate cancer may remain on low-dose prednisone or prednisolone (up to 10 mg per day) and still be eligible for this study.
Current use of prohibited medication during treatment with GSK2636771. Current use of aspirin, clopidogrel, ticlopidine, prasugrel, or ticagrelor is prohibited. Anticoagulants are permitted only if the subject meets PTT and INR entry criteria. Their use must be monitored in accordance with local institutional practice.
Active peptic ulcer disease or history of abdominal fistula, GI perforation, or intra abdominal abscess within 28 days prior to beginning study treatment.
Any major surgery within the last four weeks.
Poorly controlled hypertension (defined as systolic blood pressure of >=150 mmHg or diastolic blood pressure of >100 mmHg based on a mean of 3 measurements at approximately 2-minute intervals). NOTE: Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry.
Known active infection requiring parenteral or oral anti-infective treatment.
Evidence of severe or uncontrolled systemic diseases (e.g., unstable or uncompensated respiratory, hepatic, renal or cardiac disease).
Subjects with brain metastases of non-central nervous system (CNS) primary tumors are excluded if their brain metastases are:
QTcF interval >=470 msecs. If a screening QTcF is >=470 msecs, it should be repeated 2 additional times at least 5 minutes apart and the average of the 3 readings should be used to determine eligibility.
Other clinically significant ECG abnormalities including 2nd degree (Type II) or 3rd degree atrioventricular block.
History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within the past 6 months.
Class III or IV heart failure as defined by the New York Heart Association functional classification system.
Baseline cardiac troponin (cT-n) >10% coefficient of variance (CV).
Known hypersensitivity to any of the components of the study treatment.
Pregnant or lactating female.
Any malignancy related to human immunodeficiency virus (HIV) or solid organ transplant; history of known HIV, history of known Hepatitis B virus (HBV) surface antigen positivity (subjects with documented laboratory evidence of HBV clearance may be enrolled) or positive Hepatitis C virus antibody confirmed by recombinant immunoblot assay.
Screening Part 3 includes Pre-screening criteria (above) and
NOTE: Subjects receiving a stable (i.e., unchanged) dose of corticosteroids for >30 days or subjects who have not received corticosteroids within 14 days prior to the first dose of study treatment may be enrolled. Subjects must not have received enzyme-inducing anticonvulsants within 28 days prior to enrollment.
Primary purpose
Allocation
Interventional model
Masking
30 participants in 3 patient groups
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Data sourced from clinicaltrials.gov
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