Phase I/Ib Study of Paclitaxel in Combination With VS-6063 in Patients With Advanced Ovarian Cancer
This trial is active, not recruiting.
|Treatments||defactinib (vs-6063), paclitaxel|
|Start date||January 2013|
|End date||December 2015|
|Trial size||27 participants|
|Trial identifier||NCT01778803, VS-6063-101|
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.
|United States||No locations recruiting|
|Other countries||No locations recruiting|
|Endpoint classification||safety study|
|Intervention model||single group assignment|
Oral defactinib (VS-6063) administered twice daily, in combination with intravenous paclitaxel administered on Days 1, 8, and 15 of a 28 day cycle.
Assess the safety and tolerability of defactinib (VS-6063) when administered in combination with paclitaxel in subjects with advanced ovarian tumors
time frame: From start of treatment to end of treatment, an expected average of 12 weeks
Establish the recommended phase 2 dose (RP2D) of defactinib (VS-6063) in combination with paclitaxel in subjects with advanced ovarian tumors
time frame: From start of treatment to end of cycle 1 (4 week cycles)
Evaluate the efficacy of subjects treated with paclitaxel and defactinib (VS-6063)
time frame: Every 2 cycles up to end of treatment, an expected average of 12 weeks
Assess the pharmacokinetics (PK) of defactinib (VS-6063) when co-administered with paclitaxel
time frame: Time points at Day 1 and Day 15 in Cycle 1
Female participants at least 18 years old.
- Able to provide signed and dated informed consent prior to initiation of any study procedures.
- Female subjects aged ≥ 18 years.
- Advanced or refractory ovarian cancer, confirmed histologically.
- Subjects may have received up to 4 prior lines of chemotherapy for their metastatic disease.
- All persistent clinically significant toxicities from prior chemotherapy must be ≤ Grade 1.
- ECOG performance status of 0 or 1 (refer to Appendix A), measured within 72 hours before the start of treatment.
- Predicted life expectancy of ≥ 3 months.
- Adequate renal function [creatinine ≤ 1.5x ULN (upper limit of normal)] or GFR of ≥ 50mL/min.
- Adequate hepatic function (total bilirubin ≤ 1.5x ULN for the institution; AST [aspartate transaminase] and ALT [alanine transaminase] ≤ 3x ULN, or ≤ 5x ULN if due to liver involvement by tumor).
- Adequate bone marrow function (hemoglobin ≥ 9.0 g/dL; platelets≥ 100 x109cells/L; absolute neutrophil count ≥ 1.5x109 cells/L).
- Corrected QT interval (QTc) < 470 ms (as calculated by the Fridericia correction formula).
- Negative pregnancy test for females of child-bearing potential; must be surgically sterile, postmenopausal, or willing and able to be compliant with a contraceptive regimen (double barrier birth control) during and for 3 months after the treatment period.
- Willing and able to participate in the trial and comply with all trial requirements.
- Gastrointestinal (GI) condition which could interfere with the swallowing or absorption of study medication.
- Uncontrolled or severe concurrent medical condition (including uncontrolled brain metastases). Stable brain metastases either treated or being treated with a stable dose of steroids/anticonvulsants, with no dose change within 28 days prior to the first dose of study drug, will be allowed.
- History of upper gastrointestinal bleeding, ulceration, or perforation within 12 months prior to the first dose of study drug.
- Known history of Gilbert's Syndrome.
- Known history of stroke or cerebrovascular accident within 6 months prior to the first dose of study drug.
- Subjects with known infection with human immunodeficiency virus (HIV) or Acquired Immune Deficiency Syndrome (AIDS) (testing not required).
- Subjects with Hepatitis A, B or C (testing not required).
- Subjects being actively treated for a secondary malignancy.
- Cancer-directed therapy (chemotherapy, radiotherapy, hormonal therapy, biologic or immunotherapy, etc.) within 28 days of the first dose of study drug or 5 half-lives, whichever is shorter.
- Major surgery within 28 days prior to the first dose of study drug.
- Use of an investigational drug within 28 days or 5 half-lives (whichever is shorter) prior to the first dose of study drug. A minimum of 10 days between termination of the investigational drug and administration of the study treatment is required. In addition, any drug-related toxicity except alopecia should have recovered to grade 1 or less.
- Pregnant or breastfeeding.
- Any evidence of serious active infections.
- Uncontrolled or severe cardiovascular disease, including myocardial infarct or unstable angina within 6 months prior to study treatment, New York Heart Association (NYHA) Class II or greater congestive heart failure, serious arrhythmias requiring medication for treatment, clinically significant pericardial disease, or cardiac amyloidosis.
- Uncontrolled intercurrent illness including symptomatic congestive heart failure, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
|Official title||A Phase I/Ib Study of Paclitaxel in Combination With VS-6063, a Focal Adhesion Kinase Inhibitor, in Subjects With Advanced Ovarian Cancer|
Call for more information