Study to Assess Safety and Tolerability of Oral CC-115 for Patients With Advanced Solid Tumors, and Hematologic Malignancies.

Phase 1

Completed

• Conditions: Glioblastoma Multiforme; Squamous Cell Carcinoma of Head and Neck; Prostate Cancer; Ewing's Osteosarcoma; Neoplasm Metastasis; Chronic Lymphocytic Leukemia
• Interventions: Drug: CC-115

• Registration Number: NCT01353625
• Lead Sponsor: Celgene

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.

Study Timeline

• Study Start: 2011-04-25
• Study First Submitted: 2011-05-12
• Study First Submitted QC: 2011-05-12
• Study First Posted: 2011-05-13
• Primary Completion: 2021-03-12
• Study Completion: 2021-03-12
• Status Verified: 2021-09
• Last Update Submitted: 2021-10-04
• Last Update Posted: 2021-10-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 118

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
• Part B only: Prior treatment with agents targeting both mammalian target of rapamycin (mTOR) complexes (dual mammalian target of rapamycin complex 1/2 inhibitors) and/or PI3K/AKT pathways. However, prior treatment with isolated target of rapamycin complex 1 (TORC1) inhibitors (eg., rapalogs) is allowed in both parts of this study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CC-115	CC-115	-

Primary Outcome Measures

Name	Time	Method
Terminal Half-Life for CC-115	Days 1, 2, 15, and 16 of treatment
Time to Maximum Concentration of CC-115	Days 1, 2, 15, and 16 of treatment
Maximum Tolerated Dose	Continuously for 28 days after starting treatment
Non-Tolerated Dose	Continuously for 28 days after starting treatment
Maximum Observed Concentration in Plasma of CC-115	Days 1, 2, 15, 16 of treatment
Apparent Total Body Clearance of CC-115	Days 1, 2, 15 and 16 of treatment
Apparent Volume of Distribution of CC-115	Days 1, 2, 15, and 16 of treatment
Accumulation Index of CC-115	Days 1, 2, 15 and 16 of treatment
Dose-Limiting Toxicity	Continuously for 28 days after starting treatment
Area Under the Concentration-Time Curve for CC-115	Days 1, 2, 15 and 16 of treatment

Secondary Outcome Measures

Name	Time	Method
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	Phosphorylation inhibition determined by changes in the levels of multiple biomarkers including S6 and, 4EBP (for mTORC1), AKT (for mTORC2) and other appropriate biomarkers in circulating granulocytes and tumor tissue (when available).
Anti-Tumor Efficacy	Every 2-3 months until proof of tumor progression	Tumor response rates using appropriate objective criteria for various malignancies

Trial Locations

Locations (17)

Memorial Sloan-Kettering Cancer Center; 🇺🇸 New York, New York, United States

Universitatsklinikum Wurzburg; 🇩🇪 Würzburg, Germany

UCLA; 🇺🇸 Los Angeles, California, United States

Cedars-Sinai Medical Center; 🇺🇸 Los Angeles, California, United States

University of California, San Francisco Comprehensive Cancer Center and Cancer Research Institiute; 🇺🇸 San Francisco, California, United States

University of Michigan Comprehensive Cancer Center; 🇺🇸 Ann Arbor, Michigan, United States

Moffitt Cancer Center; 🇺🇸 Tampa, Florida, United States

Sarah Cannon Research Institute Drug Development Unit; 🇺🇸 Nashville, Tennessee, United States

Henry Ford Medical Center - New Center One; 🇺🇸 Detroit, Michigan, United States

Uniklinik Koln; 🇩🇪 Koeln, Germany

The University of Texas MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Gustave Roussy; 🇫🇷 Villejuif Cedex, France

Mary Crowley Medical Research Center; 🇺🇸 Dallas, Texas, United States

Hospital Val d'Hebron; 🇪🇸 Barcelona, Spain

Hospital Universitario Madrid Sanchinarro; 🇪🇸 Madrid, Spain

Hospital de Donosti; 🇪🇸 San Sebastián (Guipuzcoa), Spain

Hospital Virgen del Rocio; 🇪🇸 Sevilla, Spain