Clinical trial NCT01545947: Study Assessing Safety, Pharmacokinetics and Efficacy of CC-223 With Either Erlotinib or Oral Azacitidine in Advanced Non-Small Cell Lung Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
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
Lead sponsor: Celgene
Sponsor class: INDUSTRY
First posted: 2012-03-07
Enrollment: 76
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Adverse events
timeFrame: Up to 24 months
measure: MTD
timeFrame: Up to 24 months
measure: PK-Cmax
timeFrame: Up to 15 months
measure: PK-AUC
timeFrame: Up to 15 months
measure: PK-Tmax
timeFrame: Up to 15 months
measure: PK-T1/2
timeFrame: Up to 15 months
measure: PK-CL/F
timeFrame: Up to 15 months
measure: PK-Vz/F
timeFrame: Up to 15 months
Secondary outcomes:
measure: mTORC1 and mTORC2 pathway biomarkers
timeFrame: Up to 15 months.
measure: CC-223 metabolite, M1
timeFrame: Up to 9 months
measure: Tumor Response Rate
timeFrame: Up to 24 months
measure: Number of participants surviving without tumor progression
timeFrame: Up to 24 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center, Inflammatory Bowel Disease Center
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: New York
country: United States
facility: NYU School of Medicine
state: New York
city: Greenville
country: United States
facility: Cancer Center of the Carolinas
state: South Carolina
city: Nashville
country: United States
facility: Henry-Joyce Cancer Clinic
state: Tennessee
city: Dallas
country: United States
facility: Mary Crowley Cancer Research Centers - Medical City
state: Texas
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Barcelona
country: Spain
facility: Vall d´Hebron University Hospital
city: Sevilla
country: Spain
facility: Hospital Virgen del Rocio Servicio de Hematologia
Study officials:
affiliation: Celgene Corporation
name: Kristen Hege, MD
role: STUDY_DIRECTOR
References: