Phase I/Ib Study of Paclitaxel in Combination With VS-6063 in Patients With Advanced Ovarian Cancer

Inclusion criteria

• 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.

Exclusion criteria

• 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.