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.
Information provided by (Responsible Party):
Celgene ( Celgene Corporation ) Identifier:
First received: May 12, 2011
Last updated: March 10, 2016
Last verified: March 2016
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 Intervention 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

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:

Further study details as provided by Celgene:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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

Estimated Enrollment: 144
Study Start Date: April 2011
Estimated Study Completion Date: July 2016
Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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.
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Please refer to this study by its identifier: NCT01353625

United States, California
Cedars-Sinai Medical Center
Los Angeles, California, United States, 90048
Los Angeles, California, United States, 90095
University of California, San Francisco Comprehensive Cancer Center and Cancer Research Institiute
San Francisco, California, United States, 94115
United States, Florida
Moffitt Cancer Center
Tampa, Florida, United States, 33612
United States, Michigan
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States, 48109
Henry Ford Health System
Detroit, Michigan, United States, 48202
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021
United States, Tennessee
Sarah Cannon Research Institute Drug Development Unit
Nashville, Tennessee, United States, 37203
United States, Texas
Mary Crowley Medical Research Center
Dallas, Texas, United States, 75201
The University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77303
Institut Gustave Roussy
Villejuif Cedex, France, 94805
Uniklinik Koln
Koeln, Germany, 50937
Universitatsklinikum Wurzburg
Würzburg, Germany, 97070
Hospital Vall d'Hebron
Barcelona, Spain, 08035
Hospital Universitario Madrid Sanchinarro
Madrid, Spain, 28050
Hospital de Donosti
San Sebastián (Guipuzcoa), Spain, 20014
Hospital Virgen del Rocio
Sevilla, Spain, 41013
Sponsors and Collaborators
Celgene Corporation
Study Director: Kristen Hege, MD Celgene Corporation
  More Information

Responsible Party: Celgene ( Celgene Corporation ) Identifier: NCT01353625     History of Changes
Other Study ID Numbers: CC-115-ST-001 
Study First Received: May 12, 2011
Last Updated: March 10, 2016
Health Authority: United States: Federal Government
United States: Institutional Review Board
United States: Food and Drug Administration
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
France: Comité consultatif sur le traitement de l'information en matière de recherche dans le domaine de la santé
France: Committee for the Protection of Personnes
France: Conseil National de l'Ordre des Médecins
France: Direction Générale de la Santé
France: French Data Protection Authority
France: Haute Autorité de Santé Transparency Commission
France: Institutional Ethical Committee
France: Agence Nationale de Sécurité du Médicament et des produits de santé
France: Ministry of Health
France: Ministère de l'Enseignement supérieur et de la Recherche
France: National Consultative Ethics Committee for Health and Life Sciences
France: The Commission nationale de l’informatique et des libertés
Germany: Ethics Commission
Germany: Federal Institute for Drugs and Medical Devices
Germany: Federal Ministry of Education and Research
Germany: Federal Ministry of Food, Agriculture and Consumer Protection
Germany: Federal Office for Radiation Protection
Germany: German Institute of Medical Documentation and Information
Germany: Ministry of Health
Germany: Ministry of Work, Health and Social Affairs in North Rhine-Westph
Germany: Paul-Ehrlich-Institute
Germany: The Bavarian State Ministry of the Environment and Public Health
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Spain: Comité Ético de Investigación Clínica
Spain: Departament de Salut de la Generalitat de Catalunya
Spain: Ethics Committee
Spain: Ministry of Health
Spain: Ministry of Health and Consumption
Spain: Spanish Agency of Medicines

Keywords provided by Celgene:
Multiple myeloma
mTOR kinase inhibitor
Castration-resistant prostate cancer
Hormone-resistant prostate cancer
Diffuse Large B-cell lymphoma

Additional relevant MeSH terms:
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Neoplasm Metastasis
Prostatic Neoplasms
Genital Diseases, Male
Genital Neoplasms, Male
Immune System Diseases
Immunoproliferative Disorders
Leukemia, B-Cell
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neoplasms, Squamous Cell processed this record on May 23, 2016