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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
76
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
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
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
Adverse events
Number of participants with adverse events
Time frame: Up to 24 months
MTD
Maximum tolerated dose (MTD)
Time frame: Up to 24 months
PK-Cmax
Pk-Maximum observed concentration in plasma (Cmax)
Time frame: Up to 15 months
PK-AUC
Area under the plasma concentration-time curve (AUC)
Time frame: Up to 15 months
PK-Tmax
PK-Time to maximum concentration (Tmax)
Time frame: Up to 15 months
PK-T1/2
PK-Terminal half-life (T1/2)
Time frame: Up to 15 months
PK-CL/F
PK-Apparent total body clearance (CL/F)
Time frame: Up to 15 months
PK-Vz/F
PK-Apparent volume of distribution (Vz/F)
Time frame: Up to 15 months
mTORC1 and mTORC2 pathway biomarkers
The effect of treatment on mTORC1 and mTORC2 pathway biomarkers in blood and tumor
Time frame: Up to 15 months.
CC-223 metabolite, M1
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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
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
CC-223 metabolite, M1, will be characterized
Time frame: Up to 9 months
Tumor Response Rate
Tumor Response Rate using RECIST 1.1 (Eisenhauer, 2009)
Time frame: Up to 24 months
Number of participants surviving without tumor progression
Number of participants surviving without tumor progression
Time frame: Up to 24 months