This is an open-label Phase 1b/2 multicenter study of rebastinib (DCC-2036) in combination with carboplatin designed to evaluate the safety, tolerability, and pharmacokinetics (PK) in participants with advanced or metastatic solid tumors.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
70
Administered orally
Administered by IV infusion
University of California San Francisco (UCSF)
San Francisco, California, United States
UCLA Medical Center
Santa Monica, California, United States
University of Chicago
Chicago, Illinois, United States
University of Kansas Medical Center
Number of Participants With Adverse Events
Number of participants who experienced serious adverse events (SAE) and adverse events (AE).
Time frame: Baseline up to 2.32 years
Objective Response Rate (ORR) (Dose Expansion Phase)
Percentage of participants who achieved an objective response of Complete Response (CR) or Partial Response (PR) per Response Evaluation Criteria in Solid Tumor (RECIST) v1.1. CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had to have reduction in short axis to \<10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Disease progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study including baseline; or the appearance of one or more new lesions.
Time frame: Time from CR or PR to disease progression or death due to any cause (Up to 1.53 years)
Objective Response Rate (ORR) (Dose Escalation Phase)
Percentage of participants who achieved an objective response of Complete Response (CR) or Partial Response (PR) per Response Evaluation Criteria in Solid Tumor (RECIST) v1.1. CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had to have reduction in short axis to \<10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Disease progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study including baseline; or the appearance of one or more new lesions.
Time frame: Time from CR or PR to disease progression or death due to any cause (Up to 1.53 years)
Duration of Response (DOR)
Time from first partial response (PR) or complete response (CR) to disease progression (PD) or death due to any cause. Evaluation of radiographic disease assessment per Response Evaluation Criteria in Solid Tumor (RECIST v1.1). CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had to have reduction in short axis to \<10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Disease progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study including baseline; or the appearance of one or more new lesions.
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Kansas City, Kansas, United States
Levine Cancer Institute
Charlotte, North Carolina, United States
The Ohio State University
Columbus, Ohio, United States
Sarah Cannon Research Institute
Nashville, Tennessee, United States
MD Anderson Cancer Center
Houston, Texas, United States
NEXT Oncology
San Antonio, Texas, United States
Time frame: Time from PR or CR to PD or Death due to Any Cause (up to 1.53 years)
Time to Progression (TTP)
Time from first dose of study drug to the first documentation of progressive disease (PD). Participants were considered to have progressive disease if they had documented progression based on radiologic assessment according to RECIST v1.1. RECIST v1.1 defined disease progression as at least a 20% increase in the sum of the disease measurements for measurable lesions, taking as reference the smallest disease measurement recorded since the start of treatment, or the appearance of one or more new lesions.
Time frame: First Dose of Study Drug to PD (Up to 1.63 years)
Progression-free-survival (PFS)
Time from first dose of study drug to disease progression (PD) or death due to any cause. Participants who undergo surgical resection of target or non-target lesions, who have received other anticancer treatments, including surgical resection or radiation (other than palliative radiation to pre-existing bone metastases'), or who do not have a documented date of progression or death due to any cause will be censored at the date of the last assessment. Disease progression per RECIST v1.1 is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study including baseline; or the appearance of one or more new lesions.
Time frame: First Dose of Study Drug to PD or Death due to Any Cause (up to 1.63 years)
Overall Survival (OS)
Time from baseline C1 D1 to date of death due to any cause. Participants who are still alive or who are lost to follow-up will be censored at the date of last contact.
Time frame: Baseline to death due to any cause (Up to 2.12 years)
Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Rebastinib (Part 1)
Cmax of rebastinib
Time frame: Part 1: Cycle (C) 1 Day (D) 1, C2 D1 (Cycle = 21 Days)
PK: Area Under the Concentration-time Curve 0-3 Hours (AUC 0-3 Hours) (Part 1)
Measure the AUC 0-3 hours
Time frame: Part 1: Cycle (C) 1 Day (D) 1, C2 D1 (Cycle = 21 Days)