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.
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

March 2, 2012
March 17, 2014
April 2012
December 2014   (final data collection date for primary outcome measure)
  • 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)
  • Number of participants with adverse events [ Time Frame: Up to 24 months ] [ Designated as safety issue: Yes ]
    Number of participants with adverse events
  • Maximum tolerated dose (MTD) [ Time Frame: Up to 24 months ] [ Designated as safety issue: Yes ]
    Maximum tolerated dose (MTD)
  • PK-Maximum observed concentration in plasma (Cmax) [ Time Frame: Up to 15 months ] [ Designated as safety issue: No ]
    Pk-Maximum observed concentration in plasma (Cmax)
  • PK-Area under the plasma concentration-time curve (AUC) [ Time Frame: Up to 15 months ] [ Designated as safety issue: No ]
    Area under the plasma concentration-time curve (AUC)
  • PK-Time to maximum concentration (Tmax) [ Time Frame: Up to 15 months ] [ Designated as safety issue: No ]
    PK-Time to maximum concentration (Tmax)
  • PK-Terminal half-life (T1/2) [ Time Frame: Up to 15 months ] [ Designated as safety issue: No ]
    PK-Terminal half-life (T1/2)
  • PK-Apparent total body clearance (CL/F) [ Time Frame: Up to 15 months ] [ Designated as safety issue: No ]
    PK-Apparent total body clearance (CL/F)
  • PK-Apparent volume of distribution (Vz/F) [ Time Frame: Up to 15 months ] [ Designated as safety issue: No ]
    PK-Apparent volume of distribution (Vz/F)
Complete list of historical versions of study NCT01545947 on ClinicalTrials.gov Archive Site
  • 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
Same as current
Not Provided
Not Provided
 
Study Assessing Safety, Pharmacokinetics and Efficacy of CC-223 With Either Erlotinib or Oral Azacitidine in Advanced Non-Small Cell Lung Cancer
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

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.

Not Provided
Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Carcinoma, Non-Small-Cell Lung
  • Non-Small Cell Lung Cancer
  • 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
  • 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
  • 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

  • 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.
    Intervention: Drug: CC-223, erlotinib
  • 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.
    Intervention: Drug: CC-223, oral azacitidine
  • 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
    Intervention: Drug: CC-223, oral azacitidine
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
108
March 2015
December 2014   (final data collection date for primary outcome measure)

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.
Both
18 Years and older
No
Contact: Associate Director, Clinical Trials Disclosure 1-888-260-1599 clinicaltrialdisclosure@celgene.com
United States,   Spain
 
NCT01545947
CC-223-NSCL-001, 2011-005290-23
No
Celgene Corporation
Celgene Corporation
Not Provided
Study Director: Kristen Hege, MD Celgene Corporation
Celgene Corporation
March 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP