This phase I trial studies the side effects and best dose of veliparib when given together with liposomal irinotecan in treating patients with solid tumors. Liposomal irinotecan and veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
PRIMARY OBJECTIVES: I. To evaluate the safety and tolerability of escalating doses of liposomal irinotecan (MM-398) + veliparib combination. II. To determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of the combination of MM-398 + veliparib. SECONDARY OBJECTIVES: I. To observe and record anti-tumor activity. II. To characterize the preliminary efficacy of the combination using key efficacy indicators, such as objective response rate, clinical benefit rate defined as complete response (CR), partial response (PR), or stable disease (SD) at 24 weeks, and progression free survival (PFS). EXPLORATORY OBJECTIVE: I. Imaging, tumor, and blood biomarkers to assess the sensitivity or resistance to each drug and/or correlation with clinical response. OUTLINE: This is a dose-escalation study of veliparib. Patients receive liposomal irinotecan intravenously (IV) over 90 minutes on days 1 and 15 and veliparib orally (PO) twice daily (BID) on days 5-12 and 19-25 or 3-12 and 17-25. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Within 2-6 days prior to beginning liposomal irinotecan treatment, patients may optionally receive ferumoxytol (FMX) IV and undergo magnetic resonance imaging (MRI) at baseline and 24 hours after FMX infusion. After completion of study treatment, patients are followed up for 4 weeks.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
18
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, United States
National Institutes of Health Clinical Center
Bethesda, Maryland, United States
NCI - Center for Cancer Research
Bethesda, Maryland, United States
Mayo Clinic in Rochester
Rochester, Minnesota, United States
Incidence of adverse events
Will be graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (version 5.0 as of April 1, 2018). Safety and tolerability of escalating doses of liposomal irinotecan and veliparib combination will be evaluated.
Time frame: Up to 4 weeks
Maximum tolerated dose and recommended phase II dose of liposomal irinotecan in combination with veliparib
Maximum tolerated dose and recommended phase II dose of liposomal irinotecan in combination with veliparib will be determined by incidence of dose limiting toxicities, graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (version 5.0 as of April 1, 2018).
Time frame: At 28 days
Tumor response
Will be evaluated according to Response Evaluation Criteria in Solid Tumors version 1.1.
Time frame: Up to 4 weeks after completion of study treatment
Objective response rate
Will be evaluated according to Response Evaluation Criteria in Solid Tumors version 1.1.
Time frame: At 24 weeks
Clinical benefit rate defined as complete response, partial response, or stable disease
Will be evaluated according to Response Evaluation Criteria in Solid Tumors version 1.1.
Time frame: At 24 weeks
Progression free survival
Progression free survival is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.
Time frame: Duration of time from start of treatment to time of progression or death, whichever occurs first, assessed up to 4 weeks after completion of study treatment
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Undergo MRI
Given PO
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, United States
Cleveland Clinic Foundation
Cleveland, Ohio, United States