A Phase II Randomized, Double-Blind, Placebo-Controlled, Multicenter Study of VS 6063 in Subjects with Malignant Pleural Mesothelioma

Phase 1

• Conditions: MPM is a rare but aggressive tumour of the serosal surfaces (specifically the pleura and peritoneum) that is highly invasive and progresses rapidly. The main risk factor is exposure to carcinogenic silicate fibres found in asbestos, although genetic factors may also contribute. Tumours usually arise 30 or more years after exposure, and 80% occur in men.; MedDRA version: 18.0Level: PTClassification code 10059518Term: Pleural mesothelioma malignantSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2013-001033-40-BE
• Lead Sponsor: Verastem Inc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-05-06
• Last Update Posted: 22 August 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 400

Inclusion Criteria

1) Able to understand and give written informed consent and comply with study procedures.
2) Histologically proven diagnosis of MPM. All subjects must have biopsy material (archival tissue is acceptable) available for immunohistochemistry determination of Merlin status prior to enrollment.
3) Evaluable disease or measurable disease as assessed by RECIST version 1.1.
4) Received only one prior chemotherapy regimen consisting of = 4 cycles of pemetrexed/cisplatin or pemetrexed/carboplatin; subjects must have documentation of an ongoing response (confirmed PR or SD) following completion of this regimen. Subjects changing from cisplatin to carboplatin or vice versa within the same course of treatment because of platinum toxicity will be considered to have had first-line chemotherapy. Note: Subjects may have undergone previous surgical resection of their disease providing it was completed prior to initiation of chemotherapy. Refer to Appendix D for additional guidance.
5) Received last dose of prior chemotherapy within = 6 weeks of first dose of VS-6063.
6) Have completed baseline quality of life evaluation as assessed by LCSS modified for mesothelioma
7) Age = 18 years.
8) Life expectancy = 3 months.
9) All prior chemotherapy induced toxicities must have resolved to grade = 1 prior to randomization.
10) Performance status according to Karnofsky Performance Scale = 70% (after palliative measures such as pleural drainage).
11) Corrected QT interval (QTc) < 470 ms (as calculated by the Fridericia correction formula).
12) Adequate bone marrow function (hemoglobin = 9.0 g/dL; platelets = 100 x 109/L; absolute neutrophil count = 1.5 x 109/L) without the use of hematopoietic growth factors.
13) Adequate renal function (creatinine =1.5 x ULN [upper limit of normal] and/or glomerular filtration rate of = 50mL/min).
14) Adequate hepatic function (total bilirubin =1.5 x ULN; aspartate transaminase and alanine transaminase = 2.5x ULN).
15) Men and women of childbearing potential must agree to use adequate contraception (double barrier birth control) for the duration of study therapy and for 3 months after the last dose of VS 6063.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 150
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 250

Exclusion Criteria

1) Currently enrolled in (or completed within 30 days before study drug administration) another investigational drug study.
2) Gastrointestinal (GI) condition that could interfere with the swallowing or absorption of study drug.
3) History of upper GI bleeding, ulceration, or perforation within 12 months prior to the first dose of study drug.
4) Known history of Gilbert’s Syndrome.
5) Known history of stroke or cerebrovascular accident within 6 months prior to the first dose of study drug.
6) Subjects with known infection with human immunodeficiency virus or Acquired Immune Deficiency Syndrome (AIDS) (testing not required).
7) Subjects with known infection with hepatitis A, B or C virus (testing not required).
8) Any evidence of serious active infections.
9) Major surgery within 28 days prior to the first dose of study drug.
10) Uncontrolled or severe concurrent medical condition (including uncontrolled brain metastases). Stable brain metastases either treated or being treated with a stable dose of steroids and/or anticonvulsants (no dose change within 28 days prior to the first dose of study drug), will be allowed.
11) 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.
12) Known history of malignant hypertension.
13) Psychiatric illness or social situations that would limit compliance with study requirements.
14) History of another invasive malignancy in the last 5 years. Adequately treated non-invasive, non-melanoma skin cancers as well as in situ carcinoma of the cervix within the last 5 years will be allowed.
15) Prior treatment with a focal adhesion kinase (FAK) inhibitor.
16) Women who are pregnant or breastfeeding.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified