The purpose of the study is to evaluate the safety and to define the Maximal Tolerated Dose (MTD) or the Maximal Administered Dose (MAD) of oral azacitidine as a single agent and in combination with carboplatin (CBDCA) or paclitaxel protein bound particles (ABI-007,ABX) in subjects with relapsed or refractory solid tumors.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
169
CC-486 will be administered orally at doses between 100-300 mg daily for either 14 or 21 days depending on tolerability
Carboplatin will be given by intravenous (IV) infusion once every 21 Days at a dosage of AUC x 4.
ABI-007 will be administered by intravenous (IV) infusion on two of every three weeks at a dosage of 100 mg/m\^2
Scottsdale Healthcare Research Institute
Scottsdale, Arizona, United States
University of California, San Francisco
San Francisco, California, United States
Indiana University Cancer Center
Indianapolis, Indiana, United States
Karmanos Cancer Institute
Detroit, Michigan, United States
Greenville Hospital
Greenville, South Carolina, United States
Sarah Cannon Research Institute
Nashville, Tennessee, United States
South Texas Accelerated Research Therapeutics
San Antonio, Texas, United States
Centre Georges Francois Leclerc
Dijon, France
Institut Curie
Paris, France
The Netherlands Cancer Instiute Antoni Van Leeuwenhoekziekenhuis
Amsterdam, Netherlands
...and 3 more locations
Number of participants with adverse events
An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the subject's health, including laboratory test values, regardless of etiology. Any worsening (i.e., any clinically significant adverse change in the frequency or intensity.
Time frame: Up to 3 years
Cmax
Maximum observed concentration in plasma (Cmax)
Time frame: Up to 30 days
AUC
Area under the concentration-time curve (AUC)
Time frame: Up to 30 days
Tmax
Time to maximum concentration (tmax);
Time frame: Up to 30 days
T1/2
Terminal half-life (t1/2)
Time frame: Up to 30 days
CL/F
Apparent total body clearance (CL/F)
Time frame: Up to 30 days
Vz/F
Apparent volume of distribution (Vz/F).
Time frame: Up to 30 days
DNA Methylation
Change from baseline (Cycle 1 Day 1 pre-dose) in DNA methylation (global and gene-specific assays) in whole blood and tumor tissue (as available in Part 1)
Time frame: Up to 30 days
DNMT1 protein levels
Reduction from baseline (Cycle 1 Day 1 predose) in DNMT1 protein levels in tumor tissue (as available in Part 1)
Time frame: Up to 30 days
Tumor Response Rate
Response and progression were evaluated using the RECIST 1.1 criteria. Treatment response includes both complete response and partial response. * Complete response-disappearance of all lesions * Partial response-30% decrease in the sum of diameters of target lesions from baseline
Time frame: Up to 3 years
Progression Free Survival
Progression-free survival is defined as the time from first dose of study drug to the start of disease progression or patient death, whichever occurs first.
Time frame: Up to 3 years
Duration of Response
Duration of response is defined as progression-free survival in responders, i.e. as the time between the start of a complete response (CR) or partial response (PR) and the start of progressive disease (PD) or patient death from any cause, whichever occurred first
Time frame: Up to 3 years
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