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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Celgene Corporation
ClinicalTrials.gov Identifier:
NCT01353625
First received: May 12, 2011
Last updated: December 27, 2016
Last verified: December 2016

May 12, 2011
December 27, 2016
April 2011
September 2018   (Final data collection date for primary outcome measure)
  • Dose-Limiting Toxicity [ Time Frame: Continuously for 28 days after starting treatment ]
  • Non-Tolerated Dose [ Time Frame: Continuously for 28 days after starting treatment ]
  • Maximum 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 ]
  • Area Under the Concentration-Time Curve for CC-115 [ Time Frame: Days 1, 2, 15 and 16 of 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 ]
  • 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 ]
    Dose-Limiting Toxicity
  • Non-Tolerated Dose [ Time Frame: Continuously for 28 days after starting treatment ]
  • Maximum 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 ]
  • Area Under the Concentration-Time Curve for CC-115 [ Time Frame: Days 1, 2, 15 and 16 of 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 ]
  • 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 ]
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 ]
    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 ]
    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 ]
    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 ]
  • Number of participants with tumor response using appropriate objective criteria. [ Time Frame: Screening, Days 15 and 155 and end of treatment ]
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/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
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.
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.
Interventional
Phase 1
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
Thijssen R, Ter Burg J, Garrick B, van Bochove GG, Brown JR, Fernandes SM, Rodríguez 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
119
November 2018
September 2018   (Final data collection date for primary outcome measure)

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.
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States,   France,   Germany,   Spain
 
 
NCT01353625
CC-115-ST-001
No
Not Provided
Not Provided
Not Provided
Celgene Corporation
Celgene Corporation
Not Provided
Study Director: Kristen Hege, MD Celgene Corporation
Celgene Corporation
December 2016

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