An Open-Label, Phase I, Dose-Escalation Study Evaluating Two Dosing Schedules of PI3-Kinase Inhibitor (GDC-0941) in Patients With Locally Advanced or Metastatic Solid Tumors for Which Standard Therapy Either Does Not Exist or Has Proven Ineffective or Intolerable
Overview
- Phase
- Phase 1
- Intervention
- GDC-0941
- Conditions
- Solid Cancers
- Sponsor
- Genentech, Inc.
- Enrollment
- 108
- Primary Endpoint
- Terminal Elimination Half-Life (t1/2) of GDC-0941
- Status
- Completed
- Last Updated
- 9 years ago
Overview
Brief Summary
This is an open-label, multicenter, Phase I, dose-escalation study to assess the safety, tolerability, and pharmacokinetics of orally administered GDC-0941 administered once daily (QD) and twice daily (BID) in the treatment of advanced or metastatic solid tumors.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Participants with histologically documented, incurable, locally advanced or metastatic solid malignancy that has progressed or failed to respond to at least one prior regimen, and who are not candidates for regimens known to provide clinical benefit
- •Evaluable or measurable disease per RECIST
- •Life expectancy of greater than or equal to (\>/=) 12 weeks
- •Documented willingness to use an effective means of contraception (for both men and women) while participating in the study
Exclusion Criteria
- •Leptomeningeal disease as the only manifestation of the current malignancy
- •History of Type 1 or 2 diabetes mellitus requiring regular medication
- •Any condition requiring anticoagulants, such as warfarin, heparin, or thrombolytics
- •Malabsorption syndrome or other condition that would interfere with enteral absorption
- •Known untreated central nervous system (CNS) malignancies or treated brain metastases that are not radiographically stable for \>/=3 months
- •Active congestive heart failure or ventricular arrhythmia requiring medication
- •Uncontrolled ascites requiring weekly large-volume paracentesis for 3 consecutive weeks prior to enrollment
- •Active infection requiring intravenous (IV) antibiotics
- •Requirement for any daily supplemental oxygen
- •Uncontrolled hypomagnesemia or hypokalemia, defined as values below the lower limit of normal (LLN), or hypercalcemia above the upper limit of normal (ULN) for the institution despite adequate electrolyte supplementation or management
Arms & Interventions
Group A: GDC-0941 QD Dose Escalation
Participants will receive GDC-0941 for up to 1 year, administered orally QD at a starting dose of 15 milligrams (mg).
Intervention: GDC-0941
Group B: GDC-0941 BID Dose Escalation
Participants will receive GDC-0941 for up to 1 year, administered orally BID at a starting dose determined from Group A assessments.
Intervention: GDC-0941
Group C: GDC-0941 QD or BID Expansion
Participants will receive GDC-0941 for up to 1 year, administered orally QD or BID. The dose/regimen will be determined on the basis of data from Groups A and B.
Intervention: GDC-0941
Outcomes
Primary Outcomes
Terminal Elimination Half-Life (t1/2) of GDC-0941
Time Frame: Pre-dose (5 min) and post-dose (0.5, 1, 2, 3, 4, 8, 12, 24, 48, 72 h) Day 1; pre-dose (5 min) and post-dose (0.5, 1, 2, 3, 4, 8, 12, 24 h) Days 8 and 15; pre-dose (5 min) Days 22, 29, 36, and end of Cycles 1 to 12 (up to 1 year overall)
Maximum Observed Concentration (Cmax) of GDC-0941
Time Frame: Pre-dose (5 min) and post-dose (0.5, 1, 2, 3, 4, 8, 12, 24, 48, 72 h) Day 1; pre-dose (5 min) and post-dose (0.5, 1, 2, 3, 4, 8, 12, 24 h) Days 8 and 15; pre-dose (5 min) Days 22, 29, 36, and end of Cycles 1 to 12 (up to 1 year overall)
Percentage of Participants with Adverse Events
Time Frame: Visits during treatment on Days 1, 2, 3, 4, 8, 15, 22, 29, 36; weekly during Cycle 2; every two weeks during Cycles 3 to 6; every month during Cycles 7 to 12; and up to 30 days after last dose (up to 1 year overall)
Percentage of Participants with Grade 3 or 4 Abnormalities in Safety-Related Laboratory Parameters
Time Frame: Visits at Baseline and during treatment on Days 1, 8, 15, 22, 29, 36; weekly during Cycle 2; every two weeks during Cycles 3 to 6; every month during Cycles 7 to 12; and up to 30 days after last dose (up to 1 year overall)
Time of Maximum Observed Concentration (Tmax) of GDC-0941
Time Frame: Pre-dose (5 minutes [min]) and post-dose (0.5, 1, 2, 3, 4, 8, 12, 24, 48, 72 hours [h]) Day 1; pre-dose (5 min) and post-dose (0.5, 1, 2, 3, 4, 8, 12, 24 h) Days 8 and 15; pre-dose (5 min) Days 22, 29, 36, and end of Cycles 1 to 12 (up to 1 year overall)
Percentage of Participants with Dose-Limiting Toxicities (DLTs)
Time Frame: Visits during treatment on Days 1, 2, 3, 4, 8, 15, 22, 29, 36
Area Under the Concentration-Time Curve (AUC) of GDC-0941
Time Frame: Pre-dose (5 min) and post-dose (0.5, 1, 2, 3, 4, 8, 12, 24, 48, 72 h) Day 1; pre-dose (5 min) and post-dose (0.5, 1, 2, 3, 4, 8, 12, 24 h) Days 8 and 15; pre-dose (5 min) Days 22, 29, 36, and end of Cycles 1 to 12 (up to 1 year overall)
Secondary Outcomes
- Percentage of Participants by Best Overall Response According to Response Evaluation Criteria in Solid Tumors (RECIST)(Tumor assessments as Baseline, Day 36, and every 8 weeks thereafter through Cycle 12 (up to 1 year overall))
- Duration of Objective Response According to RECIST(Tumor assessments as Baseline, Day 36, and every 8 weeks thereafter through Cycle 12 (up to 1 year overall))
- Progression-Free Survival (PFS) According to RECIST(Tumor assessments as Baseline, Day 36, and every 8 weeks thereafter through Cycle 12 (up to 1 year overall))