A Phase 1 Study Evaluating CB-5083 in Subjects With Advanced Solid Tumors
- Registration Number
- NCT02243917
- Lead Sponsor
- Cleave Biosciences, Inc.
- Brief Summary
This is a multicenter, open-label, Phase 1 study of orally administered CB-5083 in adult subjects with advanced metastatic solid tumors. The study will be conducted in 2 parts: an initial Dose Escalation Phase (Phase 1a) of CB-5083 in subjects with advanced metastatic solid tumors who have progressed or are non-responsive to available therapies and for which no standard therapy exists, followed by a Dose Expansion Phase (Phase 1b) which will include 1 to 4 arms: one arm in subjects with RAS mutated mCRC; optionally, at sponsors discretion, 3 additional arms may be added for subjects with advanced RCC, advanced pNET, or solid tumors with mutations in the RAS-MAPK pathway.
- Detailed Description
The objectives of the Dose Escalation Phase are to determine the safety, tolerability, PK and pharmacodynamic profiles, the MTD and/or RP2D, and the effect of fed vs. fasted state on the bioavailability of orally administered CB-5083. The objectives of the dose expansion phase are to confirm the safety and tolerability of the RP2D, to further assess the PK and pharmacodynamic profiles and to evaluate the preliminary anti-tumor activity of CB-5083 in subjects with tumors for which there is biologic plausibility of unique sensitivity to CB-5083 mechanism of action (MOA) based on pre-clinical data. The objectives of the Food Effect Stage is to determine the effect of fed vs. fasted state on the bioavailability of orally administered CB-5083.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 62
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Dose Escalation Stage - CB-5083 CB-5083 CB-5083 will be orally administered daily, 4 days on and 3 days off, for 28 day cycles; subjects who have completed at least one cycle may optionally participate in a food effect week, wherein CB-5083 will be orally administered once daily, on days 1 and 4, and thereafter return to the original dosing schedule Dose Expansion Stage - CB-5083 CB-5083 CB-5083 will be orally administered daily, 4 days on and 3 days off, for 28 day cycles Food Effect Stage - CB-5083 CB-5083 CB-5083 will be orally administered once daily, on days 1 and 4 of week 1, cycle 1, and orally administered daily, 4 days on and 3 days off, for the remaining 3 weeks of cycle 1; for subsequent 28 day cycles, CB-5083 will be orally administered daily, 4 days on and 3 days off
- Primary Outcome Measures
Name Time Method Dose Escalation Stage - the dose limiting toxicities (DLTs), using NCI CTCAE v4.0, of oral CB-5083 in subjects with advanced tumors the first 28 days of treatment with CB-5083 Dose Escalation Stage - the pharmacokinetic profile (PK) of oral CB-5083 in subjects with advanced solid tumors; parameters include AUC, Cmax, Tmax and T1/2 day 1 to day 5 of Cycle 1 and day 1 and day 2 of Cycle 2 Dose Expansion Stage - safety and tolerability of oral CB-5083 administered to subjects with RAS mutated metastatic colorectal cancer (mCRC) at the RP2D, using NCI CTCAE v4.0 day 1 of Cycle 1 through 28 days after the subjects's last treatment Dose Expansion Stage - safety and tolerability of CB-5083 in subjects with advanced renal-cell carcinoma (RCC), pancreatic neuroendocrine tumors (pNET) or solid tumors with RAS-MAPK mutations, if such arms are opened per Sponsor, using NCI CTCAE v4.0 from day 1 of Cycle 1 through 28 days after the subjects's last treatment Food Effect Stage - the effect of a standard meal on the plasma concentration of oral CB-5083 in subjects with advanced solid tumors from day 1 of Cycle 1 through day 5 of Cycle 1
- Secondary Outcome Measures
Name Time Method Dose Expansion Stage - PK and PD profiles of CB-5083; PK parameters to include AUC, Cmax, Tmax and T1/2; PD effects through the measurement of PUA in PBMCs day 1 through day 5 of Cycle 1; day 1 and day 2 of Cycle 2 (PK only) Dose Escalation Stage - the pharmacodynamic (PD)effects of CB-5083 through the measurement of polyubiquitin accumulation (PUA) in peripheral blood mononuclear cells (PBMCs) day 1 through day 5 of Cycle 1 Dose Expansion Stage - anti-tumor activity in certain subjects, using the Response Evaluation Criteria in Solid Tumors (RECIST), v1.1 from the pre-study visit though the end of the last cycle on treatment, an expected average of 14 weeks Food Effect Stage - safety and tolerability of oral CB-5083 in subjects with advanced solid tumors using NCI CTCAE v4.0, of oral CB-5083 From day 1 of Cycle 1 through 28 days after the subjects's last treatment
Trial Locations
- Locations (6)
HonorHealth Research Institute
🇺🇸Scottsdale, Arizona, United States
University of Colorado
🇺🇸Aurora, Colorado, United States
University of Pennsylvania, Abramson Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
University of California San Francisco
🇺🇸San Francisco, California, United States
Winship Cancer Institute of Emory University
🇺🇸Atlanta, Georgia, United States
Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute
🇺🇸Los Angeles, California, United States