Overview

This trial is active, not recruiting.

Condition relapsed malignant mesothelioma
Treatment vs-5584 and vs-6063
Phase phase 1
Sponsor Verastem, Inc.
Start date January 2015
End date August 2016
Trial size 56 participants
Trial identifier NCT02372227, VS-6063-104

Summary

The purpose of this study is to evaluate rising dose levels of VS-5584 administered in combination with a fixed dose of VS-6063 in subjects with relapsed malignant mesothelioma to determine a recommended Phase 2 dose (RP2D) for further development of this combination in this indication.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
vs-5584 and vs-6063
Starting dose of VS-5584 will be 20mg taken once daily, 3x/week of each 21 day cycle. All subjects will also receive 2x/day treatment with 400mg VS-6063 in 21 day cycles. Number of Cycles: until progression or unacceptable toxicity develops.

Primary Outcomes

Measure
Incidence of dose-limiting toxicities (DLTs)
time frame: 6 months
Safety and tolerability of the combination of VS-5584 and VS-6063
time frame: 16 months

Secondary Outcomes

Measure
Pharmacokinetics of VS-5584 & VS-6063 maximum observed plasma concentration (Cmax)
time frame: 0-48 hours per patient
Pharmacokinetics of VS-5584 & VS-6063 plasma area under the curve from time zero to last quantifiable concentration (AUClast)
time frame: 0-48 hours per patient
Pharmacokinetics of VS-5584 & VS-6063 time to reach maximum observed concentration (Tmax)
time frame: 0-48 hours per patient
Pharmacokinetics of VS-5584 & VS-6063 area under the curve from time zero to extrapolated infinite time (AUCO-inf)
time frame: 0-48 hours per patient
Pharmacokinetics of VS-5584 & VS-6063 apparent oral clearance (CL/F)
time frame: 0-48 hours per patient
Pharmacokinetics of VS-5584 & VS-6063 apparent volume of distribution (Vz/F)
time frame: 0-48 hours per patient
Pharmacokinetics of VS-5584 & VS-6063 trough plasma concentration
time frame: 0-48 hours per patient

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: 1. Histopathologically-confirmed diagnosis of malignant mesothelioma (pleural or peritoneal). Must have disease that has relapsed following at least one prior line of chemotherapy. 2. Must have received at least 3 cycles of first-line chemotherapy. 3. Evaluable or measurable disease as assessed by Response Evaluation Criteria in Solid Tumors (RECIST). 4. Must have archival tumor tissue available for biomarker analysis. A study-specific tumor core biopsy, pleural effusion or ascites sample must be obtained prior to treatment if archival tissue is not available. 5. Performance status according to the Karnofsky Performance Scale ≥70%. 6. Fasting blood glucose of ≤ 140 mg/dL (7.8 mmol/L). 7. Adequate renal function (creatinine ≤ 1.5x upper limit of normal [ULN]) and/or glomerular filtration rate (GFR) of ≥50 mL/min. 8. Adequate hepatic function (total bilirubin ≤ 1.5x ULN; AST and ALT ≤ 3x ULN). 9. Adequate bone marrow function (hemoglobin ≥9.0 g/dL; platelets ≥100 x10^9 cells/L; absolute neutrophil count ≥1.5x10^9 cells/L) without the use of hematopoietic growth factors. Exclusion Criteria: 1. Have had a previous extra pleural pneumonectomy (EPP). 2. Gastrointestinal condition which could interfere with the swallowing or absorption of study drug. 3. Uncontrolled or severe concurrent medical condition (including uncontrolled brain metastases). 4. Known history of stroke or cerebrovascular accident within 6 months prior to the first dose of study drug. 5. Any evidence of serious active infection. 6. Undergoing active treatment for a secondary malignancy. 7. Cancer-directed therapy (chemotherapy, radiotherapy) within 21 days of the first dose of study drug or 5 half-lives, whichever is shorter. 8. Major surgery within 28 days prior to the first dose of study drug. 9. Acute or chronic pancreatitis. 10. Diabetes mellitus requiring insulin treatment or subjects with a hemoglobin A1C (HbA1C) >7%. 11. History or evidence of cardiac risk. 12. Known history of malignant hypertension.

Additional Information

Official title A Phase 1 Dose Escalation Study of VS-5584, a Dual PI3K/mTOR Inhibitor, Administered With a Fixed Dose of VS-6063, a Focal Adhesion Kinase Inhibitor, in Subjects With Relapsed Malignant Mesothelioma
Description This study is comprised of 2 sequential parts: Part 1 (Dose Escalation of VS-5584) and Part 2 (Expansion). Up to 56 evaluable subjects (i.e., subjects who complete at least 1 cycle [21 days] of therapy) will be enrolled, assuming that: - Up to 6 dose levels of VS-5584 are studied in Part 1 (Dose Escalation of VS-5584) in combination with a fixed dose of VS-6063 at 400 mg twice daily (BID) with a maximum of 6 subjects enrolled per VS-5584 dose level, for a total of up to 36 subjects (exclusive of replacement subjects). - Up to an additional 20 evaluable subjects may be enrolled in Part 2, the expansion portion of the study. Subjects will be treated with VS-5584 at the RP2D and schedule determined in the dose escalation portion of the study in combination with a fixed dose of VS-6063.
Trial information was received from ClinicalTrials.gov and was last updated in January 2016.
Information provided to ClinicalTrials.gov by Verastem, Inc..
Location data was received from the National Cancer Institute and was last updated in April 2016.