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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 has been completed.
Sponsor:
Information provided by (Responsible Party):
Celgene
ClinicalTrials.gov Identifier:
NCT01177397
First received: August 5, 2010
Last updated: May 11, 2017
Last verified: May 2017
  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: Intervention Model: Single Group Assignment
Masking: No masking
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:

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 ]
    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. ]
    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. ]
    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 ]
    Tumor response rates using appropriate objective criteria for various malignancies


Enrollment: 173
Actual Study Start Date: July 20, 2010
Study Completion Date: December 9, 2016
Primary Completion Date: November 15, 2016 (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: (closed to enrollment) 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   (Adult, Senior)
Sexes Eligible for Study:   All
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

Locations
United States, California
Cedars-Sinai Medical Center
Los Angeles, California, United States, 90048
UCLA Neuro-Oncology Program
Los Angeles, California, United States, 90095
University of California, San Francisco Hellen Diller Family Comprehensive Cancer Center
San Francisco, California, United States, 94115
United States, Florida
Moffitt Cancer Center
Tampa, Florida, United States, 33612
United States, Minnesota
Mayo Clinic Cancer Clinical Studies Unit
Rochester, Minnesota, United States, 55905
United States, Montana
Billings Clinic
Billings, Montana, United States, 59102
United States, New Jersey
Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
United States, New York
NYU Cancer Institute - Bellevue Hospital
New York, New York, United States, 10016
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
France
Institut Claudius Regaud
Toulouse Cedex, France, 31052
Institut Gustave Roussy Faculte de Medecine Paris Sud Service de pneumologie
Villejuif, France, 94800
Spain
Hospital Universitario de Salamanca
Salamanca, Spain, 37007
Hospital Universitario Virgen Del Rocio
Sevilla, Spain, 41013
United Kingdom
Sarah Cannon Research Institute UK
London, United Kingdom, W1G 6AD
UCL Cancer Institute
London, United Kingdom, WC1E 6BT
Sponsors and Collaborators
Celgene
Investigators
Study Director: Kristen Hege, M.D. Celgene
  More Information

Responsible Party: Celgene
ClinicalTrials.gov Identifier: NCT01177397     History of Changes
Other Study ID Numbers: CC-223-ST-001
Study First Received: August 5, 2010
Last Updated: May 11, 2017

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

Additional relevant MeSH terms:
Lymphoma
Carcinoma, Non-Small-Cell Lung
Multiple Myeloma
Neoplasms, Plasma Cell
Lymphoma, Non-Hodgkin
Glioblastoma
Carcinoma, Hepatocellular
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neuroendocrine Tumors
Carcinoid Tumor
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders

ClinicalTrials.gov processed this record on July 21, 2017