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

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Celgene Corporation
Sponsor:
Information provided by (Responsible Party):
Celgene Corporation
ClinicalTrials.gov Identifier:
NCT01545947
First received: March 2, 2012
Last updated: March 17, 2014
Last verified: March 2014
  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
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: 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 ] [ Designated as safety issue: Yes ]
    Number of participants with adverse events

  • MTD [ Time Frame: Up to 24 months ] [ Designated as safety issue: Yes ]
    Maximum tolerated dose (MTD)

  • PK-Cmax [ Time Frame: Up to 15 months ] [ Designated as safety issue: No ]
    Pk-Maximum observed concentration in plasma (Cmax)

  • PK-AUC [ Time Frame: Up to 15 months ] [ Designated as safety issue: No ]
    Area under the plasma concentration-time curve (AUC)

  • PK-Tmax [ Time Frame: Up to 15 months ] [ Designated as safety issue: No ]
    PK-Time to maximum concentration (Tmax)

  • PK-T1/2 [ Time Frame: Up to 15 months ] [ Designated as safety issue: No ]
    PK-Terminal half-life (T1/2)

  • PK-CL/F [ Time Frame: Up to 15 months ] [ Designated as safety issue: No ]
    PK-Apparent total body clearance (CL/F)

  • PK-Vz/F [ Time Frame: Up to 15 months ] [ Designated as safety issue: No ]
    PK-Apparent volume of distribution (Vz/F)


Secondary Outcome Measures:
  • mTORC1 and mTORC2 pathway biomarkers [ Time Frame: Up to 15 months. ] [ Designated as safety issue: No ]
    The effect of treatment on mTORC1 and mTORC2 pathway biomarkers in blood and tumor

  • CC-223 metabolite, M1 [ Time Frame: Up to 9 months ] [ Designated as safety issue: No ]
    CC-223 metabolite, M1, will be characterized

  • Tumor Response Rate [ Time Frame: Up to 24 months ] [ Designated as safety issue: No ]
    Tumor Response Rate using RECIST 1.1 (Eisenhauer, 2009)

  • Number of participants surviving without tumor progression [ Time Frame: Up to 24 months ] [ Designated as safety issue: No ]
    Number of participants surviving without tumor progression


Estimated Enrollment: 108
Study Start Date: April 2012
Estimated Study Completion Date: March 2015
Estimated 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 erlotonib, 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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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 with tumor progression following at least one prior treatment regimen (either chemotherapy or an Epidermal Growth Factor Receptor inhibitor) for advanced disease. There is no restriction on the number of prior treatment regimens allowed.
  2. Eastern Cooperative Oncology Group 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, HbA1c > 6.5%.
  7. Known Human Immunodeficiency Virus, chronic hepatitis B or C infection.
  8. Prior treatment with an investigational dual TORC1/TORC2, PI3K, or Akt inhibitor. Prior treatment with 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
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: NCT01545947

Contacts
Contact: Associate Director, Clinical Trials Disclosure 1-888-260-1599 clinicaltrialdisclosure@celgene.com

Locations
United States, California
Cedars Sinai Recruiting
Los Angeles, California, United States, 90048
University of California San Francisco Recruiting
San Francisco, California, United States, 94115
United States, New York
NYU Cancer Institute Recruiting
New York, New York, United States, 10016
United States, South Carolina
ITOR Cancer Center of North Carolina Recruiting
Greenville, South Carolina, United States, 29605
United States, Tennessee
Vanderbilt University Medical Center Recruiting
Nashville, Tennessee, United States, 37232
Contact: Cancer Information Program    800-811-8480      
Principal Investigator: Dr. Leora Horn         
United States, Texas
Mary Crowley Cancer Research Center Recruiting
Dallas, Texas, United States, 75201
Principal Investigator: John Nemunaitis, MD         
University of Texas MD Anderson Recruiting
Houston, Texas, United States, 77030
Spain
Hospital Universitari Vall d'Hebron Recruiting
Barcelona, Spain, 08035
Contact: Dr.Enriqueta Felip    +34 93 2746077    efelip@vhebron.net   
Principal Investigator: Dr. Enriqueta Felip         
Hospital Universitario Virgen del Rocío Recruiting
Sevilla, Spain, 41013
Contact: Ana Calderon    +34 955 013068    ana.calderon.exts@juntadeandalucia.es   
Contact: Laura Bernal    +34 955 013068    lbernal@andaluciajunta.es   
Principal Investigator: Luis Paz-Ares, MD         
Hospital Universitario Clínico de Valencia Not yet recruiting
Valencia, Spain, 46010
Contact: Amparo Domingo    +34 963987649    domingo_amp@gva.es   
Contact: Inmaculada Blasco    +34 963987649    inmablasco@hotmail.com   
Principal Investigator: Amelia Insa, MD         
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: NCT01545947     History of Changes
Other Study ID Numbers: CC-223-NSCL-001, 2011-005290-23
Study First Received: March 2, 2012
Last Updated: March 17, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Spain: Agencia Española de Medicamentos y Productos Sanitarios

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
Carcinoma
Lung Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Azacitidine
Erlotinib
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on July 26, 2014