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

NCT ID: NCT01545947

Last Updated: 2019-11-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 76 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-05-01
• Study Completion Date: 2014-12-11

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

CC-223, erlotinib

Intervention Type: 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/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.

Group Type: EXPERIMENTAL

CC-223, oral azacitidine

Intervention Type: 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 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

Group Type: EXPERIMENTAL

CC-223, oral azacitidine

Intervention Type: DRUG

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

Interventions

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

Intervention Type: 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

Intervention Type: 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

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Celgene

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kristen Hege, MD

Role: STUDY_DIRECTOR

Celgene Corporation

Locations

Cedars Sinai Medical Center, Inflammatory Bowel Disease Center

Los Angeles, California, United States

University of California, San Francisco

San Francisco, California, United States

NYU School of Medicine

New York, New York, United States

Cancer Center of the Carolinas

Greenville, South Carolina, United States

Henry-Joyce Cancer Clinic

Nashville, Tennessee, United States

Mary Crowley Cancer Research Centers - Medical City

Dallas, Texas, United States

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Vall d´Hebron University Hospital

Barcelona, , Spain

Hospital Virgen del Rocio Servicio de Hematologia

Seville, , Spain

Countries

United States; Spain

Other Identifiers

2011-005290-23

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CC-223-NSCL-001

Identifier Type: -

Identifier Source: org_study_id