Study to Assess Safety, Pharmacokinetics, and Efficacy of Oral CC-223 for Patients With Advanced Solid Tumors, Non-Hodgkin Lymphoma or Multiple Myeloma

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2013 by Celgene Corporation
Sponsor:
Information provided by (Responsible Party):
Celgene Corporation
ClinicalTrials.gov Identifier:
NCT01177397
First received: August 5, 2010
Last updated: July 17, 2013
Last verified: July 2013
  Purpose

The main purpose of this first human study with CC-223 is to assess the safety and action of a new class of experimental drug (dual mTOR inhibitors) in patients with advanced tumors unresponsive to standard therapies and to determine the appropriate dose and tumor type for later-stage clinical trials.


Condition Intervention Phase
Multiple Myeloma
Diffuse Large B-Cell Lymphoma
Glioblastoma Multiforme
Hepatocellular Carcinoma
Non-Small Cell Lung Cancer
Neuroendocrine Tumors of Non-Pancreatic Origin
Hormone Receptor-Positive Breast Cancer
Drug: CC-223
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1/2, Multi-Center, Open-Label, Dose Finding Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of the mTOR Kinase Inhibitor CC-223 Administered Orally to Subjects With Advanced Solid Tumors, Non-Hodgkin Lymphoma or Multiple Myeloma.

Resource links provided by NLM:


Further study details as provided by Celgene Corporation:

Primary Outcome Measures:
  • Safety [ Time Frame: From the time of informed consent, throughout dosing period and for 21 days after the last dose of CC-223 ] [ Designated as safety issue: Yes ]
    To determine the safety profile and dose-limiting toxicity of CC-223 using NCI CTCAE v4.

  • Pharmacokinetics [ Time Frame: Throughout the first cycle (30 days) through to the first day of Cycle 2. ] [ Designated as safety issue: No ]
    Standard variables (eg. Cmax, AUC, half-life) to define the PK profile for single and multiple doses of oral CC-223.


Secondary Outcome Measures:
  • Pharmacodynamics [ Time Frame: Throughout the first cycle (30 days) through to the first day of Cycle 2. ] [ Designated as safety issue: No ]
    Phosphorylation inhibition changes by levels of S6, 4EBP (for mTORC1) and AKT (for mTORC2) in circulating granulocytes, and tumor tissue (when available).

  • 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: 230
Study Start Date: July 2010
Estimated Study Completion Date: February 2016
Estimated Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CC-223
All patients will receive CC-223, but serial patient groups will receive different dose levels in Phase 1. The number of groups will be determined by the number of dose levels required to establish dose-limiting toxicity.
Drug: CC-223

Part A: (closed to enrollment) Dose level starts with 7.5mg daily taken by mouth in cycles of 28 days. Level increases for different patient cohorts in 100% or 50% increments until optimal dose level is established for further study. Treatment continues for as long as patient benefits (i.e., until disease progression or unacceptable toxicity).

Part B: (actively recruiting) Optimal dose is administered in 28 day cycles until disease progression.


Detailed Description:

Initially, patients will be treated with oral CC-223 for one month. During this time, various tests (involving blood and urine collections, ECGs, etc) will be performed. Those whose tumors stabilize or regress may continue receiving treatment for as long as they benefit from CC-223. Different dose levels of CC-223 will be tested in a dose-rising study design.

  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, Non-Hodgkin Lymphoma or multiple myeloma
  • Patients have not tolerated or progressed on standard therapy, and no further standard therapy is available
  • Archival and screening tumor biopsy
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (solid tumors), 0-2 (hematologic malignancy)
  • Adequate organ function

Exclusion Criteria:

  • Prior systemic cancer-directed treatments or investigational drugs within 4 weeks or 5 half lives, whichever is shorter, prior to starting study drug or who have not recovered from side effects of such therapy. Subjects must have recovered from any effects of recent radiotherapy that might confound the safety evaluation of study drug
  • Symptomatic brain metastases (prior Rx and stable metastases are OK)
  • Acute or chronic liver or renal disease or pancreatitis
  • Diarrhea ≥ Grade 2, impaired GI absorption
  • Impaired cardiac function
  • Diabetes requiring Rx, glucose >126 mg/dL, HbA1c ≥6.5%
  • Peripheral neuropathy ≥ Grade 2
  • Pulmonary fibrosis
  • Known HIV infection
  • Known chronic hepatitis B or C virus (HBV/HCV) infection, unless comorbidity in subjects with HCC
  • Pregnant, inadequate contraception
  • Most concurrent second malignancies
  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: NCT01177397

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

Locations
United States, California
Cedars-Sinai Medical Center-Samuel Oschin Comprehensive Cancer Institute Recruiting
Los Angeles, California, United States, 90048
Contact: Regina Deck    310-967-4397    Regina.Deck@cshs.org   
UCLA Neuro-Oncology Program Completed
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    pfiermonte@medicine.ucsf.edu   
Principal Investigator: Pamela Munster, MD         
United States, Florida
Moffitt Cancer Center & Research Institute Recruiting
Tampa, Florida, United States, 33612
Contact: Jennifer Cooksey, BS, CCRP    813-745-4740    Jennifer.Cooksey@moffitt.org   
United States, Minnesota
Mayo Clinic Completed
Rochester, Minnesota, United States, 55905
United States, Montana
Billings Clinic Terminated
Billings, Montana, United States, 59101
United States, New Jersey
John Theurer Cancer Center at Hackensack University Recruiting
Hackensack, New Jersey, United States, 07601
Contact: Danielle Schillen, R.N.    201-336-8849    dschillen@humed.com   
United States, New York
NYU Cancer Institute Recruiting
New York, New York, United States, 10016
Contact: Nicholas B. Shuman, MSN, RN    212-263-9091    Nicholas.Shuman@nyumc.org   
United States, Tennessee
Sarah Cannon Research Institute (SCRI) Recruiting
Nashville, Tennessee, United States, 37203
Contact: Vicky D. Weikal    615-524-4052    Vicky.Weikal@scresearch.net   
Principal Investigator: Johanna Bendell, M.D         
United States, Texas
Mary Crowley Cancer Research Centers Recruiting
Dallas, Texas, United States, 75230
Contact: Meghan Degele    972-566-3062    mdegele@marycrowley.org   
France
Institut Claudius Régaud Recruiting
Toulouse Cedex, France, 31052
Contact: Jean-Pierre Delord    +33567222567    delord.jean-pierre@claudiusregaud.fr   
Institut Gustave Roussy, Dept. of Medicine Recruiting
Villejuif Cedex, France, 94800
Contact: Natacha Colin    +33142114952    natacha.colin@igr.fr   
Spain
Hospital Universitario de Salamanca Recruiting
Salamanca, Spain, 37007
Contact: Irene Real    +34923291384    ireal@usal.es   
Servicio de Oncologia Medica Sala de Investigación Recruiting
Seville, Spain, 41013
Contact: Ana Calderon    +0034955013068    ana.calderon.exts@juntadeandalucia.es   
United Kingdom
Sarah Cannon Research Institute Recruiting
London, United Kingdom, W1G 6AD
Contact: Janet Shadare    +44 (0) 203 219 5220    Janet.Shadare@HCAHealthcare.co.uk   
University College London Hospitals NHS Foundation Trust Recruiting
London, United Kingdom, NW1 2BU
Contact: Alan Sahin    +44 (0) 845 1555 000 ext 76043    Alan.Sahin@uclh.nhs.uk   
Sponsors and Collaborators
Celgene Corporation
Investigators
Study Director: Kristen Hege, M.D. Celgene Corporation
  More Information

No publications provided

Responsible Party: Celgene Corporation
ClinicalTrials.gov Identifier: NCT01177397     History of Changes
Other Study ID Numbers: CC-223-ST-001
Study First Received: August 5, 2010
Last Updated: July 17, 2013
Health Authority: 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
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
United States: Food and Drug Administration
United States: Institutional Review Board
United Kingdom: Department of Health
United Kingdom: Food Standards Agency
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: National Health Service
United Kingdom: National Institute for Health Research
United Kingdom: Research Councils UK
United Kingdom: Research Ethics Committee

Keywords provided by Celgene Corporation:
Advanced solid malignant neoplasms,Non-Hodgkin Lymphoma,
Multiple Myeloma

Additional relevant MeSH terms:
Breast Neoplasms
Carcinoma, Hepatocellular
Carcinoma, Non-Small-Cell Lung
Glioblastoma
Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Non-Hodgkin
Multiple Myeloma
Neoplasms, Plasma Cell
Neuroendocrine Tumors
Adenocarcinoma
Astrocytoma
Blood Protein Disorders
Breast Diseases
Bronchial Neoplasms
Carcinoma
Carcinoma, Bronchogenic
Cardiovascular Diseases
Digestive System Diseases
Digestive System Neoplasms
Glioma
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Liver Diseases
Liver Neoplasms
Lung Diseases

ClinicalTrials.gov processed this record on October 22, 2014