A Phase 1a/1b, Multicenter, Open Label, Dosefinding Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of the Dual Dna-pk and Tor Kinase Inhibitor, Cc-115, Administered Orally to Subjects With Advanced Solid Tumors and Hematologic Malignancies
Overview
- Phase
- Phase 1
- Intervention
- CC-115
- Conditions
- Glioblastoma Multiforme
- Sponsor
- Celgene
- Enrollment
- 118
- Locations
- 17
- Primary Endpoint
- Maximum Tolerated Dose
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
The main purpose of this first human study with CC-115 is to assess the safety and action of a new class of experimental drug (dual DNA-PK and TOR kinase inhibitors) in patients with advanced tumors unresponsive to standard therapies and to determine the appropriate dose and tumor types for later-stage clinical trials. The bioavailability of tablet and capsule formulations under fasting and fed conditions will also be evaluated in some patients.
Detailed Description
Latest amendment clarifies that Chronic Lymophocytic Leukemia (CLL) includes T-cell Prolymphocytic Leukemia (T-PLL). Prior treatment with some drugs targeting mTOR, P13K and related pathways is now permitted.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically-confirmed advanced solid tumor, chronic lymphocytic leukemia, small lymphocytic lymphoma, T-cell prolymphocytic leukemia, Non-Hodgkin Lymphoma or multiple myeloma
- •Progressed or not tolerated standard therapy, and no further standard therapy is available
- •Archival and screening tumor biopsy
- •Eastern Cooperative Oncology Group Performance Status: 0 or 1
- •Adequate organ function
Exclusion Criteria
- •Prior cancer-directed modalities or investigational drugs within 4 wks or 5 half lives, whichever is shorter
- •Symptomatic brain metastases (prior treatment and stable metastases are allowed)
- •Acute or chronic renal disease or pancreatitis
- •Diarrhea ≥ Grade 2, impaired gastrointestinal absorption
- •Impaired cardiac function
- •History of diabetes requiring treatment, glucose \>126 mg/dL, Glycated hemoglobin (HbA1c) ≥6.5%
- •Peripheral neuropathy ≥ Grade 2
- •Known Human Immunodeficiency Virus (HIV) infection, chronic hepatitis B or C (unless associated with hepatocellular cancer)
- •Pregnant, inadequate contraception, breast feeding
- •Most concurrent second malignancies
Arms & Interventions
CC-115
Intervention: CC-115
Outcomes
Primary Outcomes
Maximum Tolerated Dose
Time Frame: Continuously for 28 days after starting treatment
Time to Maximum Concentration of CC-115
Time Frame: Days 1, 2, 15, and 16 of treatment
Terminal Half-Life for CC-115
Time Frame: Days 1, 2, 15, and 16 of treatment
Non-Tolerated Dose
Time Frame: Continuously for 28 days after starting treatment
Maximum Observed Concentration in Plasma of CC-115
Time Frame: Days 1, 2, 15, 16 of treatment
Apparent Total Body Clearance of CC-115
Time Frame: Days 1, 2, 15 and 16 of treatment
Apparent Volume of Distribution of CC-115
Time Frame: Days 1, 2, 15, and 16 of treatment
Accumulation Index of CC-115
Time Frame: Days 1, 2, 15 and 16 of treatment
Dose-Limiting Toxicity
Time Frame: Continuously for 28 days after starting treatment
Area Under the Concentration-Time Curve for CC-115
Time Frame: Days 1, 2, 15 and 16 of treatment
Secondary Outcomes
- Pharmacodynamics(Screening (within 28 days prior to first dose of study drug) and Days 1, 2, 8, 15, 22, 28, 155, and end of treatment)
- Anti-Tumor Efficacy(Every 2-3 months until proof of tumor progression)