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. (see Contacts and Locations)
Verified September 2014 by Celgene Corporation
Sponsor:
Information provided by (Responsible Party):
Celgene Corporation
ClinicalTrials.gov Identifier:
NCT01353625
First received: May 12, 2011
Last updated: September 11, 2014
Last verified: September 2014
  Purpose

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/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.

Resource links provided by NLM:


Further study details as provided by Celgene Corporation:

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: November 2015
Estimated Primary Completion Date: July 2015 (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.

  Eligibility

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

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01353625

Contacts
Contact: Wayne R. Hull 1-908-673-9727 whull@celgene.com

Locations
United States, California
Cedars-Sinai Medical Center Recruiting
Los Angeles, California, United States, 90048
Contact: Regina Deck    310-967-4397    Regina.Deck@cshs.org   
UCLA Neuro-Oncology Program Active, not recruiting
Los Angeles, California, United States, 90095-1769
University of California at San Francisco Recruiting
San Francisco, California, United States, 94115
Contact: Paula Fiermonte, RN    415-885-7605      
United States, Florida
Moffitt Cancer Center & Research Institute Recruiting
Tampa, Florida, United States, 33612
Contact: Angela Akar    214-658-1964    Angela.Akar@Moffitt.org   
United States, Michigan
University of Michigan, Comprehensive Cancer Center Active, not recruiting
Ann Arbor, Michigan, United States, 48109-5940
Karmanos Cancer Center Withdrawn
Detroit, Michigan, United States, 48201
Henry Ford Health System Active, not recruiting
Detroit, Michigan, United States, 48202
United States, New York
Memorial Sloan-Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Dana Rathkopf, MD    646-422-4379    rathkopd@MSKCC.ORG   
NYU Clinical Cancer Center Withdrawn
New York, New York, United States, 10016
United States, Tennessee
Sarah Cannon Research Institute (SCRI) Drug Development Unit Recruiting
Nashville, Tennessee, United States, 37203
Contact: Vicky D Weikal    615-524-4052    Vicky.Weikal@scresearch.net   
United States, Texas
Mary Crowley Cancer Research Centers Recruiting
Dallas, Texas, United States, 75230
Contact: Meghan Degele    972-566-3062    mdegele@marycrowley.org   
The University of Texas, MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Sandy Molina    713-792-8370    smolina@mdanderson.org   
France
Department of Medical Oncology-Institut Gustave Roussy Recruiting
Villejuif, France, 94800
Contact: Christophe Massard, MD    +33142115210    christophe.massard@igr.fr   
Germany
Uniklinik Koln Recruiting
Koeln, Germany, 50937
Contact: Barbara Eichhorst    49 221478      
Universitatsklinikum Wuerzburg Recruiting
Wuerzburg, Germany, 97080
Spain
Hospital Universitario Vall Hebrón Recruiting
Barcelona, Spain, 08035
Contact: Josep Tabernero, MD    34 93 489 4301    jtabernero@vhio.net   
Unidad de Fase I 3º planta Hospital Universitario Madrid Sanchinarro Recruiting
Madrid, Spain, 28050
Contact: Manuel Hidalgo    34 91 756 78 25    mhidalgo@cnio.es   
Hospital de Donosti Recruiting
San Sebastian, Spain, 20014
Contact: Enrique Bengoechea    003494300700 ext 3232    enrique.bengoecheanerecan@osakidetza.net   
Pasillo Onco-Hematología. Sala de Protocolos Hospital Universitario Virgen del Rocío Recruiting
Sevilla, Spain, 41013
Contact: Luis Paz-Ares, MD    34 955014134    luis.pazares.sspa@juntadeandalucia.es   
Sponsors and Collaborators
Celgene Corporation
Investigators
Study Director: Kristen Hege, MD Celgene Corporation
  More Information

No publications provided

Responsible Party: Celgene Corporation
ClinicalTrials.gov Identifier: NCT01353625     History of Changes
Other Study ID Numbers: CC-115-ST-001
Study First Received: May 12, 2011
Last Updated: September 11, 2014
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 Corporation:
Neoplasm
Malignancy
Carcinoma
Lymphoma
Leukemia
Multiple myeloma
mTOR kinase inhibitor
Castration-resistant prostate cancer
Hormone-resistant prostate cancer
Diffuse Large B-cell lymphoma

Additional relevant MeSH terms:
Neoplasms
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Carcinoma, Squamous Cell
Prostatic Neoplasms
Osteosarcoma
Glioblastoma
Neoplasm Metastasis
Leukemia
Carcinoma
Head and Neck Neoplasms
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Neoplasms, Glandular and Epithelial
Neoplasms, Squamous Cell
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Sarcoma
Astrocytoma
Glioma

ClinicalTrials.gov processed this record on September 16, 2014