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

Sponsor

Celgene (Industry)

Overall Status

Completed

CT.gov ID

NCT01353625

Collaborator

(none)

118

Enrollment

Locations

Arm

118.6

Actual Duration (Months)

6.9

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Glioblastoma Multiforme Squamous Cell Carcinoma of Head and Neck Prostate Cancer Ewing's Osteosarcoma Chronic Lymphocytic Leukemia Neoplasm Metastasis	Drug: CC-115	Phase 1

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 Design

Study Type:

Interventional

Actual Enrollment :

118 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Apr 25, 2011

Actual Primary Completion Date :

Mar 12, 2021

Actual Study Completion Date :

Mar 12, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CC-115	Drug: CC-115 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.

Arm

Intervention/Treatment

Experimental: CC-115

Drug: CC-115

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.

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cedars-Sinai Medical Center	Los Angeles	California	United States	90048
2	UCLA	Los Angeles	California	United States	90095
3	University of California, San Francisco Comprehensive Cancer Center and Cancer Research Institiute	San Francisco	California	United States	94115
4	Moffitt Cancer Center	Tampa	Florida	United States	33612
5	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109
6	Henry Ford Medical Center - New Center One	Detroit	Michigan	United States	48202
7	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10021
8	Sarah Cannon Research Institute Drug Development Unit	Nashville	Tennessee	United States	37203
9	Mary Crowley Medical Research Center	Dallas	Texas	United States	75201
10	The University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77303
11	Gustave Roussy	Villejuif Cedex		France	94805
12	Uniklinik Koln	Koeln		Germany	50937
13	Universitatsklinikum Wurzburg	Würzburg		Germany	97070
14	Hospital Val d'Hebron	Barcelona		Spain	08035
15	Hospital Universitario Madrid Sanchinarro	Madrid		Spain	28050
16	Hospital de Donosti	San Sebastián (Guipuzcoa)		Spain	20014
17	Hospital Virgen del Rocio	Sevilla		Spain	41013