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

NCT01778803 | Completed Phase 1 DMC

• 1 other identifier: VS-6063-101
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Ovarian Cancer

Outcome Measures

Primary Outcomes (2)

• 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

  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

  From start of treatment to end of cycle 1 (4 week cycles)

Secondary Outcomes (5)

• 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

  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.

  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)

  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)

  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)

  Time points at Day 1 and Day 15 in Cycle 1

Other Outcomes (2)

• Evaluate biomarkers of defactinib (VS-6063) activity

  Day 1 and Day 10 of treatment

• Examine if the tumor expression status correlates with response to defactinib (VS-6063) therapy

  From start of treatment to end of treatment, an expected average of 12 weeks

Study Arms (1)

defactinib (VS-6063) plus paclitaxel

EXPERIMENTAL

Oral defactinib (VS-6063) administered twice daily, in combination with intravenous paclitaxel administered on Days 1, 8, and 15 of a 28 day cycle.

Drug: defactinib; Drug: Paclitaxel

Interventions

defactinib DRUG

Also known as: VS-6063

defactinib (VS-6063) plus paclitaxel

Paclitaxel DRUG

Also known as: Taxol

defactinib (VS-6063) plus paclitaxel

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Verastem, Inc.: lead

Study Sites (3)

Florida Cancer Specialists

Sarasota, Florida, United States

Location

University of Oklahoma

Oklahoma City, Oklahoma, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

defactinib; Paclitaxel

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Hagop Youssoufian, MD

  Verastem, Inc.

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 22, 2013
• First Posted: January 29, 2013
• Study Start: February 26, 2013
• Primary Completion: February 23, 2015
• Study Completion: February 23, 2015
• Last Updated: May 17, 2017

Record last verified: 2017-01

Locations

US (3)