This is a Phase I/Ib, open-label, multicenter, dose-escalation trial of paclitaxel in combination with defactinib (VS-6063), a focal adhesion kinase inhibitor, in patients with advanced ovarian cancer. This clinical study is comprised of 2 parts: Phase I (Dose Escalation) and Phase Ib (Expansion). The purpose of this study is to assess assess the safety (including the recommended phase 2 dose), the pharmacokinetics, and the anti-cancer activity of defactinib (VS-6063) when administered in combination with paclitaxel. Pharmacodynamic effects will also be examined in tumor biopsies.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
22
Florida Cancer Specialists
Sarasota, Florida, United States
University of Oklahoma
Oklahoma City, Oklahoma, United States
Sarah Cannon Research Institute
Nashville, Tennessee, United States
Number of patients experiencing treatment-related adverse events as assessed by CTCAE v4.03 (Common Toxicity Criteria for Adverse Effects)during the study (safety and tolerability).
Adverse events and their frequency, duration and severity, as determined based on CTCAE 4.03
Time frame: From start of treatment to end of treatment, an expected average of 12 weeks
Determine the recommended phase 2 dose (RP2D) based on a combination of maximum tolerated dosed (MTD), review of adverse event data and review of AUC, Tmax and t1/2 obtained from PK data during the dose escalation phase of the study.
The RP2D will be determined based on the maximum tolerated dose (MTD) of defactinib (VS-6063) in combination with paclitaxel as determined by number of participants with dose limiting toxicities (DLTs) related to defactinib in combination with paclitaxel
Time frame: From start of treatment to end of cycle 1 (4 week cycles)
Proportion of patients treated with paclitaxel and defactinib (VS-6063) with progression-free survival using Response Evaluation Criteria In Solid Tumors (RECIST), version 1.1
Response rate and progression-free survival, as determined by Response Evaluation Criteria In Solid Tumors (RECIST), version 1.1
Time frame: Every 2 cycles up to end of treatment, an expected average of 12 weeks
Pharmacokinetics (PK) estimates of defactinib (VS-6063) when co-administered with paclitaxel, AUC (Area Under Curve) 0-t.
Plasma concentration of defactinib (VS-6063)
Time frame: Time points at Day 1 and Day 15 in Cycle 1
Pharmacokinetics (PK) estimates of defactinib (VS-6063) when co-administered with paclitaxel, maximum concentrations (Cmax)
Plasma concentration of defactinib (VS-6063)
Time frame: Time points at Day 1 and Day 15 in Cycle 1
Pharmacokinetics (PK) estimates of defactinib (VS-6063) when co-administered with paclitaxel, Time to maximum concentrations (Tmax)
Plasma concentration of defactinib (VS-6063)
Time frame: Time points at Day 1 and Day 15 in Cycle 1
Pharmacokinetics (PK) estimates of defactinib (VS-6063) when co-administered with paclitaxel, , estimates of concentration 1/2 life (T1/2)
Plasma concentration of defactinib (VS-6063)
Time frame: Time points at Day 1 and Day 15 in Cycle 1
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