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

This study is currently recruiting participants.
Verified March 2014 by Celgene Corporation
Sponsor:
Information provided by (Responsible Party):
Celgene Corporation
ClinicalTrials.gov Identifier:
NCT01353625
First received: May 12, 2011
Last updated: March 6, 2014
Last verified: March 2014

May 12, 2011
March 6, 2014
April 2011
December 2014   (final data collection date for primary outcome measure)
  • Dose-Limiting Toxicity [ Time Frame: Continuously for 28 days after starting treatment ] [ Designated as safety issue: Yes ]
  • Non-Tolerated Dose [ Time Frame: Continuously for 28 days after starting treatment ] [ Designated as safety issue: Yes ]
  • Maximum Tolerated Dose [ Time Frame: Continuously for 28 days after starting treatment ] [ Designated as safety issue: Yes ]
  • Maximum Observed Concentration in Plasma of CC-115 [ Time Frame: Days 1, 2, 15, 16 of treatment ] [ Designated as safety issue: Yes ]
  • Area Under the Concentration-Time Curve for CC-115 [ Time Frame: Days 1, 2, 15 and 16 of treatment ] [ Designated as safety issue: Yes ]
  • Time to Maximum Concentration of CC-115 [ Time Frame: Days 1, 2, 15, and 16 of treatment ] [ Designated as safety issue: Yes ]
  • Terminal Half-Life for CC-115 [ Time Frame: Days 1, 2, 15, and 16 of treatment ] [ Designated as safety issue: Yes ]
  • Apparent Total Body Clearance of CC-115 [ Time Frame: Days 1, 2, 15 and 16 of treatment ] [ Designated as safety issue: Yes ]
  • Apparent Volume of Distribution of CC-115 [ Time Frame: Days 1, 2, 15, and 16 of treatment ] [ Designated as safety issue: Yes ]
  • Accumulation Index of CC-115 [ Time Frame: Days 1, 2, 15 and 16 of treatment ] [ Designated as safety issue: Yes ]
  • Dose-Limiting Toxicity [ Time Frame: Continuously for 28 days after starting treatment ] [ Designated as safety issue: Yes ]
    Dose-Limiting Toxicity
  • Non-Tolerated Dose [ Time Frame: Continuously for 28 days after starting treatment ] [ Designated as safety issue: Yes ]
  • Maximum Tolerated Dose [ Time Frame: Continuously for 28 days after starting treatment ] [ Designated as safety issue: Yes ]
  • Maximum Observed Concentration in Plasma of CC-115 [ Time Frame: Days 1, 2, 15, 16 of treatment ] [ Designated as safety issue: Yes ]
  • Area Under the Concentration-Time Curve for CC-115 [ Time Frame: Days 1, 2, 15 and 16 of treatment ] [ Designated as safety issue: Yes ]
  • Time to Maximum Concentration of CC-115 [ Time Frame: Days 1, 2, 15, and 16 of treatment ] [ Designated as safety issue: Yes ]
  • Terminal Half-Life for CC-115 [ Time Frame: Days 1, 2, 15, and 16 of treatment ] [ Designated as safety issue: Yes ]
  • Apparent Total Body Clearance of CC-115 [ Time Frame: Days 1, 2, 15 and 16 of treatment ] [ Designated as safety issue: Yes ]
  • Apparent Volume of Distribution of CC-115 [ Time Frame: Days 1, 2, 15, and 16 of treatment ] [ Designated as safety issue: Yes ]
  • Accumulation Index of CC-115 [ Time Frame: Days 1, 2, 15 and 16 of treatment ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT01353625 on ClinicalTrials.gov Archive Site
  • Pharmacodynamics [ Time Frame: Screening (within 28 days prior to first dose of study drug) and Days 1, 2, 8, 15, 22, 28, 155, and end of treatment ] [ Designated as safety issue: No ]
    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 [ Time Frame: Every 2-3 months until proof of tumor progression ] [ Designated as safety issue: No ]
    Tumor response rates using appropriate objective criteria for various malignancies
  • Pharmacodynamics [ Time Frame: Screening and Days 1, 2, 8, 15, 22, 28, 155, and end of treatment ] [ Designated as safety issue: No ]
    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).
  • Inhibition of biomarker DNA-PK activity in skin biopsies. [ Time Frame: Screening and Day 15 ] [ Designated as safety issue: No ]
  • Number of participants with tumor response using appropriate objective criteria. [ Time Frame: Screening, Days 15 and 155 and end of treatment ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Study to Assess Safety and Tolerability of Oral CC-115 for Patients With Advanced Solid Tumors, and Hematologic Malignancies.
A Phase 1a/b, Multicenter, Open Label, Dose-Finding 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.

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.

The bioavailability sub-study is designed as a short adjunct prior to the start of the 28-day treatment and evaluation phase of the main study and will be conducted in a limited number of US sites. Subjects with most forms of solid tumor will be eligible. Subjects participating in the preliminary bioavailability study undergo slightly fewer study-related assessments during the main part of the study than other subjects.

Interventional
Phase 1
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Glioblastoma Multiforme
  • Squamous Cell Carcinoma of Head and Neck
  • Prostate Cancer
  • Ewing's Osteosarcoma
  • Chronic Lymphocytic Leukemia
  • Neoplasm Metastasis
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.

Experimental: CC-115
Intervention: Drug: CC-115
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
144
April 2015
December 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Histologically-confirmed advanced solid tumor, chronic lymphocytic leukemia, small lymphocytic lymphoma, 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.
Both
18 Years and older
No
Contact: Wayne R. Hull 1-908-673-9727 whull@celgene.com
United States,   France,   Germany,   Spain
 
NCT01353625
CC-115-ST-001
No
Celgene Corporation
Celgene Corporation
Not Provided
Study Director: Kristen Hege, MD Celgene Corporation
Celgene Corporation
March 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP