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Study Assessing Safety, Pharmacokinetics and Efficacy of CC-223 With Either Erlotinib or Oral Azacitidine in Advanced Non-Small Cell Lung Cancer

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01545947
First Posted: March 7, 2012
Last Update Posted: November 8, 2016
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Celgene Corporation
  Purpose
The main purpose of this first study combining an investigational dual mTOR inhibitor, CC-223, with other agents (erlotinib or the investigational agent, oral azacitidine) is to establish a maximum tolerated dose level for each combination in order to evaluate their effects in future clinical trials for advanced non-small cell lung cancer.

Condition Intervention Phase
Carcinoma, Non-Small-Cell Lung Non-Small Cell Lung Cancer Drug: CC-223, erlotinib Drug: CC-223, oral azacitidine Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A PHASE 1B, MULTI-CENTER, OPEN-LABEL STUDY OF THE MTOR KINASE INHIBITOR CC-223 IN COMBINATION WITH ERLOTINIB OR ORAL AZACITIDINE IN ADVANCED NON-SMALL CELL LUNG CANCER

Resource links provided by NLM:


Further study details as provided by Celgene Corporation:

Primary Outcome Measures:
  • Adverse events [ Time Frame: Up to 24 months ]
    Number of participants with adverse events

  • MTD [ Time Frame: Up to 24 months ]
    Maximum tolerated dose (MTD)

  • PK-Cmax [ Time Frame: Up to 15 months ]
    Pk-Maximum observed concentration in plasma (Cmax)

  • PK-AUC [ Time Frame: Up to 15 months ]
    Area under the plasma concentration-time curve (AUC)

  • PK-Tmax [ Time Frame: Up to 15 months ]
    PK-Time to maximum concentration (Tmax)

  • PK-T1/2 [ Time Frame: Up to 15 months ]
    PK-Terminal half-life (T1/2)

  • PK-CL/F [ Time Frame: Up to 15 months ]
    PK-Apparent total body clearance (CL/F)

  • PK-Vz/F [ Time Frame: Up to 15 months ]
    PK-Apparent volume of distribution (Vz/F)


Secondary Outcome Measures:
  • mTORC1 and mTORC2 pathway biomarkers [ Time Frame: Up to 15 months. ]
    The effect of treatment on mTORC1 and mTORC2 pathway biomarkers in blood and tumor

  • CC-223 metabolite, M1 [ Time Frame: Up to 9 months ]
    CC-223 metabolite, M1, will be characterized

  • Tumor Response Rate [ Time Frame: Up to 24 months ]
    Tumor Response Rate using RECIST 1.1 (Eisenhauer, 2009)

  • Number of participants surviving without tumor progression [ Time Frame: Up to 24 months ]
    Number of participants surviving without tumor progression


Enrollment: 76
Study Start Date: May 2012
Study Completion Date: December 2014
Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CC-223/erlotinib concurrent
Cohorts will receive escalating continuous daily doses (15 mg and 30 mg) of CC-223 in capsules concurrently with at least two different daily dose levels of erlotinib tablets (100 mg and 150 mg) in 28-day cycles.
Drug: CC-223, erlotinib

Dose escalation: Combination doses start with 15 mg CC-223 and 100 mg erlotinib, or 15 mg CC-223 and 150 mg erlotinib, administered in 28-day cycles. Combination dose levels increase sequentially using predefined regimens until non-tolerated dose levels are established and a maximum tolerated dose combination has been identified for further study.

Dose expansion: The maximum tolerated doses are evaluated further for evidence of preliminary efficacy

Experimental: CC-223/oral azacitidine concurrent
Cohorts will receive escalating continuous daily doses of CC-223 (15 mg and 30 mg) with one or more dose levels of oral azacitidine (200 mg or 300 mg, as two or three 100 mg tablets) administered on Day 1 to 21 of each 28-day cycle.
Drug: CC-223, oral azacitidine

Dose escalation: Combination doses start with 15 mg CC-223 and 200 mg oral azacitidine, administered in 28-day cycle. Combination dose levels increase sequentially using predefined regimens until non-tolerated dose levels are established and a maximum tolerated dose combination has been identified for further study.

Dose expansion: The maximum tolerated doses are evaluated further for evidence of preliminary efficacy

Experimental: CC-223/oral azacitidine sequential
Cohorts will receive escalating continuous daily dose levels of CC-223 (15 mg and 30 mg) administered on Days 8 through 28 sequentially with one or more dose levels of of oral azacitidine (200 mg or 300 mg, as two or three 100 mg tablets) administered on Days 1 to 7 of each 28-day cycle
Drug: CC-223, oral azacitidine

Dose escalation: Sequential dosing starts with 200 mg of oral azacitidine administered on Days 1 through 7 of each 28-day cycle, followed by daily dose level of 15 mg CC-223 on Days 8 through 28. Combination dose levels increase sequentially using predefined regimens until non-tolerated dose levels are established and a maximum tolerated dose combination has been identified for further study.

Dose expansion: The maximum tolerated doses are evaluated further for evidence of preliminary efficacy


  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Men and women, 18 years or older, with histologically or cytologically-confirmed, Stage IIIB/IV Non-Small Cell Lung Cancer (NSCLC) with tumor progression following at least one prior treatment regimen [(either chemotherapy or an Epidermal Growth Factor Receptor inhibitor (EGFR)] for advanced disease. There is no restriction on the number of prior treatment regimens allowed.
  2. Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 to 1.
  3. Adequate organ function.
  4. Adequate contraception (if appropriate).
  5. Consent to retrieve archival tumor tissue.
  6. Consent to repeated tumor biopsy (dose expansion phase).

Exclusion Criteria:

  1. Prior systemic cancer-directed treatments or investigational drugs within 4 weeks or 5 half lives, whichever is shorter except erlotinib which may be continued with intervention in subjects allocated in Arm A.
  2. Symptomatic central nervous system metastases.
  3. Acute or chronic pancreatitis.
  4. Persistent diarrhea or malabsorption > Grade 2, despite medical management.
  5. Impaired cardiac function or significant cardiac disease.
  6. Diabetes on active treatment, fasting blood glucose > 126 mg/dL, (glycated haemoglobin) HbA1c > 6.5%.
  7. Known Human Immunodeficiency Virus (HIV), chronic hepatitis B or C infection.
  8. Prior treatment with an investigational dual target of ripamycin 1 (TORC1)/ target of ripamycin 2 (TORC2), Phosphatidylinositol 3-Kinase (PI3K), or protein kinase B (Akt) inhibitor. Prior treatment with analogs of rapamycin (rapalogs) is allowed.
  9. Major surgery < 2 weeks prior to starting study drugs. No specific wash out is required for radiotherapy. Subjects must have recovered from any effects of recent therapy that might confound the safety evaluation of study drug.
  10. Pregnant or breastfeeding, inadequate contraception.
  11. History of concurrent second malignancies requiring ongoing systemic treatment.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01545947


Locations
United States, California
Cedars Sinai Medical Center, Inflammatory Bowel Disease Center
Los Angeles, California, United States, 90048
University of California, San Francisco
San Francisco, California, United States, 9411
United States, New York
NYU School of Medicine
New York, New York, United States, 10016
United States, South Carolina
Cancer Center of the Carolinas
Greenville, South Carolina, United States, 29605
United States, Tennessee
Henry-Joyce Cancer Clinic
Nashville, Tennessee, United States, 37232-5505
United States, Texas
Mary Crowley Cancer Research Centers - Medical City
Dallas, Texas, United States, 75201
The University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Spain
Vall d´Hebron University Hospital
Barcelona, Spain, 08035
Hospital Virgen del RocíoServicio de Hematologia
Sevilla, Spain, 41013
Sponsors and Collaborators
Celgene Corporation
Investigators
Study Director: Kristen Hege, MD Celgene Corporation
  More Information

Responsible Party: Celgene Corporation
ClinicalTrials.gov Identifier: NCT01545947     History of Changes
Other Study ID Numbers: CC-223-NSCL-001
2011-005290-23 ( EudraCT Number )
First Submitted: March 2, 2012
First Posted: March 7, 2012
Last Update Posted: November 8, 2016
Last Verified: November 2016

Keywords provided by Celgene Corporation:
Neoplasms
Pulmonary
Lung Cancer
Cancer of the Lung
Stage IIIB Non-Small Cell Lung Cancer
IV Non-Small Cell Lung Cancer
Non-Small Cell Lung Cancer

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Erlotinib Hydrochloride
Azacitidine
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites