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

NCT01545947 | Completed Phase 1

• 2 other identifiers: CC-223-NSCL-0012011-005290-23
• Study Type: interventional
• Target: 76
• Locations: 2 countries
• Sites: 9

Brief Summary

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.

Conditions

Carcinoma, Non-Small-Cell Lung; Non-Small Cell Lung Cancer

Keywords

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

Outcome Measures

Primary Outcomes (8)

• Adverse events

  Number of participants with adverse events

  Up to 24 months

• MTD

  Maximum tolerated dose (MTD)

  Up to 24 months

• PK-Cmax

  Pk-Maximum observed concentration in plasma (Cmax)

  Up to 15 months

• PK-AUC

  Area under the plasma concentration-time curve (AUC)

  Up to 15 months

• PK-Tmax

  PK-Time to maximum concentration (Tmax)

  Up to 15 months

• PK-T1/2

  PK-Terminal half-life (T1/2)

  Up to 15 months

• PK-CL/F

  PK-Apparent total body clearance (CL/F)

  Up to 15 months

• PK-Vz/F

  PK-Apparent volume of distribution (Vz/F)

  Up to 15 months

Secondary Outcomes (4)

• mTORC1 and mTORC2 pathway biomarkers

  Up to 15 months.

• CC-223 metabolite, M1

  Up to 9 months

• Tumor Response Rate

  Up to 24 months

• Number of participants surviving without tumor progression

  Up to 24 months

Study Arms (3)

CC-223/erlotinib concurrent

EXPERIMENTAL

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

CC-223/oral azacitidine concurrent

EXPERIMENTAL

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

CC-223/oral azacitidine sequential

EXPERIMENTAL

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

Interventions

CC-223, erlotinib DRUG

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

CC-223/erlotinib concurrent

CC-223, oral azacitidine DRUG

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

CC-223/oral azacitidine concurrent

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Eastern Cooperative Oncology Group Performance Score of 0 to 1.
• Adequate organ function.
• Adequate contraception (if appropriate).
• Consent to retrieve archival tumor tissue.
• Consent to repeated tumor biopsy (dose expansion phase).

You may not qualify if:

• 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.
• Symptomatic central nervous system metastases.
• Acute or chronic pancreatitis.
• Persistent diarrhea or malabsorption \> Grade 2, despite medical management.
• Impaired cardiac function or significant cardiac disease.
• Diabetes on active treatment, fasting blood glucose \> 126 mg/dL, HbA1c \> 6.5%.
• Known Human Immunodeficiency Virus, chronic hepatitis B or C infection.
• Prior treatment with an investigational dual TORC1/TORC2, PI3K, or Akt inhibitor. Prior treatment with rapalogs is allowed.
• 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.
• Pregnant or breastfeeding, inadequate contraception.
• History of concurrent second malignancies requiring ongoing systemic treatment.

Sponsors & Collaborators

• Celgene: lead

Study Sites (9)

Cedars Sinai Medical Center, Inflammatory Bowel Disease Center

Los Angeles, California, 90048, United States

Location

University of California, San Francisco

San Francisco, California, 9411, United States

Location

NYU School of Medicine

New York, New York, 10016, United States

Location

Cancer Center of the Carolinas

Greenville, South Carolina, 29605, United States

Location

Henry-Joyce Cancer Clinic

Nashville, Tennessee, 37232-5505, United States

Location

Mary Crowley Cancer Research Centers - Medical City

Dallas, Texas, 75201, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Vall d´Hebron University Hospital

Barcelona, 08035, Spain

Location

Hospital Virgen del Rocio Servicio de Hematologia

Seville, 41013, Spain

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Neoplasms; Lung Neoplasms

Interventions

CC-223; Erlotinib Hydrochloride; Azacitidine

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Kristen Hege, MD

  Celgene Corporation

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 2, 2012
• First Posted: March 7, 2012
• Study Start: May 1, 2012
• Primary Completion: December 11, 2014
• Study Completion: December 11, 2014
• Last Updated: November 12, 2019

Record last verified: 2019-11

Locations

ES (2); US (7)