Clinical trial NCT02651727: Ph 1 Study of VS-4718, a FAK Inhibitor, in Combination With Nab-paclitaxel and Gemcitabine in Advanced Cancer Subjects
Official title: A Phase 1 Study of VS-4718, a Focal Adhesion Kinase Inhibitor, in Combination With Nab-paclitaxel and Gemcitabine in Subjects With Advanced Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Pancreatic Cancer
Lead sponsor: Verastem, Inc.
Sponsor class: INDUSTRY
First posted: 2016-01-11
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate increasing dose levels of VS-4718 administered in combination with gemcitabine and nab-paclitaxel in subjects with advanced cancer and to determine a recommended Phase 2 dose (RP2D) for further development of this combination in subjects with untreated advanced pancreatic cancer.

Detailed description: The study is comprised of 2 sequential parts: Part A (Dose Escalation of VS-4718) in subjects with advanced cancer and Part B (Expansion) in subjects with untreated advanced pancreatic cancer.

Up to 60 evaluable subjects (i.e., subjects who complete at least 1 cycle (28 days) of therapy) will be enrolled, assuming that:

1. Part A: The maximum sample size will be 6 subjects up to 4 dose levels (exclusive of replacement subjects). However, additional subjects may be added if exploration of intermediate dose level(s) of VS 4718 is warranted. The starting dose of VS-4718 will be 200mg BID.
2. Part B: Up to 36 additional subjects may be enrolled at the RP2D. These subjects will be randomized at a 1:1 ratio to 1 of 2 treatment cohorts:

   * Cohort 1: IV treatment in 28-day cycles (nab-paclitaxel 125 mg/m2 over 30 minutes on Days 1, 8, and 15 and gemcitabine at 1000 mg/m2 over 30 minutes on Days 1, 8, and 15) and oral VS 4718 BID continuously starting on Day 1 of Cycle 1
   * Cohort 2: IV treatment for the first 2 cycles, followed by IV treatment and oral VS-4718 BID continuously starting on Day 1 of Cycle 3

Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years
* Histologically or cytologically confirmed diagnosis of an advanced nonhematological malignancy (Part A) or advanced pancreatic adenocarcinoma (Part B) that is not surgically resectable
* Eligible for treatment with nab-paclitaxel and gemcitabine on Days 1, 8, and 15 in 28-day cycles as standard therapy
* Evaluable or measurable disease, as assessed by RECIST v1.1
* ECOG performance status of ≤ 1
* Adequate renal function (creatinine ≤ 1.5×ULN \[upper limit of normal\]) or glomerular filtration rate of ≥ 60 mL/min
* Adequate hepatic function (total bilirubin ≤ 1.5×ULN for the institution; aspartate transaminase and alanine transaminase ≤ 2.5×ULN, or ≤ 5×ULN if due to liver involvement by tumor; albumin ≥ 3 g/dL)
* Adequate bone marrow function (hemoglobin ≥ 9.0 g/dL; unsupported platelets ≥ 100×109 cells/L; absolute neutrophil count \[ANC\] ≥ 1.5×109 cells/L without the use of hematopoietic growth factors)
* Corrected QT interval (QTc) \< 470 ms
* Willing and able to participate in the trial and comply with all trial requirements

Exclusion Criteria:

* Gastrointestinal (GI) condition that could interfere with the swallowing or absorption of study medication
* Uncontrolled or severe concurrent medical condition (including uncontrolled brain metastases).
* History of upper gastrointestinal bleeding, ulceration, or perforation within 6 months prior to the first dose of protocol therapy
* Known history of stroke or cerebrovascular accident within 6 months prior to the first dose of protocol therapy.
* Part B only: Prior therapy (including investigational agents) for pancreatic cancer
* Chemotherapy or radiotherapy within 14 days prior to first dose of protocol therapy
* Active treatment for a secondary malignancy

Primary outcomes:
measure: Incidence of dose-limiting toxicities (DLTs)
timeFrame: 6 months
Secondary outcomes:
measure: Progression Free Survival
timeFrame: From the date of first treatment to the date of progression including death from any cause, expected average at least 5 months
measure: Response rate (RR)
timeFrame: Every 8 weeks from baseline through the end of treatment, an expected average of 5 months]
measure: Pharmacokinetics of VS-4718 in combination with nab-paclitaxel and gemcitabine: Clearance
timeFrame: Time points on Day 1, 2,15, 16, and 22 in Cycle 1; Day 1 of each subsequent cycle
measure: Pharmacokinetics of VS-4718 in combination with nab-paclitaxel and gemcitabine: Plasma concentration
timeFrame: Time points on Day 1, 2,15, 16, and 22 in Cycle 1; Day 1 of each subsequent cycle
measure: Pharmacokinetics of VS-4718 in combination with nab-paclitaxel and gemcitabine: Area under the plasma concentration versus time curve (AUC)
timeFrame: Time points on Day 1, 2,15, 16, and 22 in Cycle 1; Day 1 of each subsequent cycle
measure: Pharmacokinetics of VS-4718 in combination with nab-paclitaxel and gemcitabine: Maximum observed plasma concentration (Cmax)
timeFrame: Time points on Day 1, 2,15, 16, and 22 in Cycle 1; Day 1 of each subsequent cycle
measure: Pharmacokinetics of VS-4718 in combination with nab-paclitaxel and gemcitabine: Time to reach maximum observed concentration (Tmax)
timeFrame: Time points on Day 1, 2,15, 16, and 22 in Cycle 1; Day 1 of each subsequent cycle
measure: Pharmacokinetics of VS-4718 in combination with nab-paclitaxel and gemcitabine: Half life (T1/2)
timeFrame: Time points on Day 1, 2,15, 16, and 22 in Cycle 1; Day 1 of each subsequent cycle
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Gettysburg
country: United States
facility: Gettysburg Cancer Center
state: Pennsylvania
Study officials:
affiliation: Verastem, Inc.
name: Hagop Youssoufian, MD
role: STUDY_CHAIR
References: