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

Phase 1

Completed

• Conditions: Non-Small Cell Lung Cancer; Carcinoma, Non-Small-Cell Lung
• Interventions: Drug: CC-223, erlotinib; Drug: CC-223, oral azacitidine

• Registration Number: NCT01545947
• Lead Sponsor: Celgene

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2012-03-02
• Study First Submitted QC: 2012-03-02
• Study First Posted: 2012-03-07
• Study Start: 2012-05-01
• Primary Completion: 2014-12-11
• Study Completion: 2014-12-11
• Status Verified: 2019-11
• Last Update Submitted: 2019-11-07
• Last Update Posted: 2019-11-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 76

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CC-223/erlotinib concurrent	CC-223, erlotinib	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.
CC-223/oral azacitidine concurrent	CC-223, oral azacitidine	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.
CC-223/oral azacitidine sequential	CC-223, oral azacitidine	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

Primary Outcome Measures

Name	Time	Method
MTD	Up to 24 months	Maximum tolerated dose (MTD)
PK-AUC	Up to 15 months	Area under the plasma concentration-time curve (AUC)
PK-Vz/F	Up to 15 months	PK-Apparent volume of distribution (Vz/F)
PK-CL/F	Up to 15 months	PK-Apparent total body clearance (CL/F)
Adverse events	Up to 24 months	Number of participants with adverse events
PK-Cmax	Up to 15 months	Pk-Maximum observed concentration in plasma (Cmax)
PK-T1/2	Up to 15 months	PK-Terminal half-life (T1/2)
PK-Tmax	Up to 15 months	PK-Time to maximum concentration (Tmax)

Secondary Outcome Measures

Name	Time	Method
CC-223 metabolite, M1	Up to 9 months	CC-223 metabolite, M1, will be characterized
Tumor Response Rate	Up to 24 months	Tumor Response Rate using RECIST 1.1 (Eisenhauer, 2009)
mTORC1 and mTORC2 pathway biomarkers	Up to 15 months.	The effect of treatment on mTORC1 and mTORC2 pathway biomarkers in blood and tumor
Number of participants surviving without tumor progression	Up to 24 months	Number of participants surviving without tumor progression

Trial Locations

Locations (9)

NYU School of Medicine; 🇺🇸 New York, New York, 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; 🇪🇸 Sevilla, Spain

Henry-Joyce Cancer Clinic; 🇺🇸 Nashville, Tennessee, United States

Cancer Center of the Carolinas; 🇺🇸 Greenville, South Carolina, United States

University of California, San Francisco; 🇺🇸 San Francisco, California, United States

Cedars Sinai Medical Center, Inflammatory Bowel Disease Center; 🇺🇸 Los Angeles, California, United States