Study to Assess Safety and Tolerability of Oral CC-115 for Patients With Advanced Solid Tumors, and Hematologic Malignancies.
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
1 other identifier
interventional
118
4 countries
17
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Apr 2011
Longer than P75 for phase_1
17 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
April 25, 2011
CompletedFirst Submitted
Initial submission to the registry
May 12, 2011
CompletedFirst Posted
Study publicly available on registry
May 13, 2011
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 12, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
March 12, 2021
CompletedOctober 5, 2021
September 1, 2021
9.9 years
May 12, 2011
October 4, 2021
Conditions
Keywords
Outcome Measures
Primary Outcomes (10)
Dose-Limiting Toxicity
Continuously for 28 days after starting treatment
Non-Tolerated Dose
Continuously for 28 days after starting treatment
Maximum Tolerated Dose
Continuously for 28 days after starting treatment
Maximum Observed Concentration in Plasma of CC-115
Days 1, 2, 15, 16 of treatment
Area Under the Concentration-Time Curve 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
Terminal Half-Life for CC-115
Days 1, 2, 15, and 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
Secondary Outcomes (2)
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
Study Arms (1)
CC-115
EXPERIMENTALInterventions
Part A (actively recruiting): Dose level starts with 0.5mg daily by mouth in cycles of 28 days. Level increases for different patient cohorts in 100% or 50% increments until optimal dose schedule is established for further study. Treatment continues for as long as patient benefits (i.e., until disease progression or unacceptable toxicity). Part B: Optimal dose schedule is administered in 28-day cycles until disease progression.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Celgenelead
Study Sites (17)
Cedars-Sinai Medical Center
Los Angeles, California, 90048, United States
UCLA
Los Angeles, California, 90095, United States
University of California, San Francisco Comprehensive Cancer Center and Cancer Research Institiute
San Francisco, California, 94115, United States
Moffitt Cancer Center
Tampa, Florida, 33612, United States
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, 48109, United States
Henry Ford Medical Center - New Center One
Detroit, Michigan, 48202, United States
Memorial Sloan-Kettering Cancer Center
New York, New York, 10021, United States
Sarah Cannon Research Institute Drug Development Unit
Nashville, Tennessee, 37203, United States
Mary Crowley Medical Research Center
Dallas, Texas, 75201, United States
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77303, United States
Gustave Roussy
Villejuif, 94805, France
Uniklinik Koln
Cologne, 50937, Germany
Universitatsklinikum Wurzburg
Würzburg, 97070, Germany
Hospital Val d'Hebron
Barcelona, 08035, Spain
Hospital Universitario Madrid Sanchinarro
Madrid, 28050, Spain
Hospital de Donosti
San Sebastián (Guipuzcoa), 20014, Spain
Hospital Virgen del Rocio
Seville, 41013, Spain
Related Publications (2)
Thijssen R, Ter Burg J, Garrick B, van Bochove GG, Brown JR, Fernandes SM, Rodriguez MS, Michot JM, Hallek M, Eichhorst B, Reinhardt HC, Bendell J, Derks IA, van Kampen RJ, Hege K, Kersten MJ, Trowe T, Filvaroff EH, Eldering E, Kater AP. Dual TORK/DNA-PK inhibition blocks critical signaling pathways in chronic lymphocytic leukemia. Blood. 2016 Jul 28;128(4):574-83. doi: 10.1182/blood-2016-02-700328. Epub 2016 May 27.
PMID: 27235137BACKGROUNDMunster P, Mita M, Mahipal A, Nemunaitis J, Massard C, Mikkelsen T, Cruz C, Paz-Ares L, Hidalgo M, Rathkopf D, Blumenschein G Jr, Smith DC, Eichhorst B, Cloughesy T, Filvaroff EH, Li S, Raymon H, de Haan H, Hege K, Bendell JC. First-In-Human Phase I Study Of A Dual mTOR Kinase And DNA-PK Inhibitor (CC-115) In Advanced Malignancy. Cancer Manag Res. 2019 Dec 13;11:10463-10476. doi: 10.2147/CMAR.S208720. eCollection 2019.
PMID: 31853198DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Bristol-Myers Squibb
Bristol-Myers Squibb
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 12, 2011
First Posted
May 13, 2011
Study Start
April 25, 2011
Primary Completion
March 12, 2021
Study Completion
March 12, 2021
Last Updated
October 5, 2021
Record last verified: 2021-09