MPM is a rare but aggressive tumor 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 fibers found in asbestos, although genetic factors may also contribute. VS- 6063 is being studied as a maintenance treatment in subjects with MPM whose disease has not progressed (confirmed PR or SD) after adequate first-line treatment with pemetrexed plus platinum based chemotherapy. M
Conditions
Interventions
Product Name: VS-6063
Product Code: VS-6063
Pharmaceutical Form: Tablet
INN or Proposed INN: VS-6063
CAS Number: 1073160-26-5
Current Sponsor code: VS-6063
Other descriptive name: VS-6063
Concentratio
Sponsors
Verastem Inc
Eligibility
Sex/Gender
All
Inclusion criteria
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) =65 years) yes F.1.3.1 Number of subjects for this age range 250
Exclusion criteria
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. 14) Prior treatment with a focal adhesion kinase (FAK) inhibitor. 15) Women who are pregnant or breastfeeding.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To compare the overall survival (OS) in subjects with malignant pleural mesothelioma receiving VS-6063 or placebo. • To compare the progression free survival (PFS) in subjects with malignant pleural mesothelioma receiving VS-6063 or placebo. ;Secondary Objective: • To assess Quality of Life (QoL) in subjects treated with VS-6063 or placebo using the Lung Cancer Symptom Scale modified for mesothelioma (LCSS-Meso). • To determine the objective response rate (ORR) and time to new lesion in subjects receiving VS 6063 or placebo. Exploratory Objectives • To determine the time to new lesion in subjects receiving VS-6063 or placebo. • To evaluate the relationship of VS 6063 pharmacokinetics and outcome. • To evaluate the population pharmacokinetics of VS 6063 in subjects with malignant pleural mesothelioma. • To collect EuroQol 5-Dimensional Health Questionnaire (EQ-5D) for health economics purposes. Safety Objectives • To evaluate the safety and tolerability of VS 6063 in subjects with malignant pleural mesothelioma;Primary end point(s): Primary Efficacy Endpoints: 1) Overall Survival For all subjects, OS will be calculated from the date of randomization to the date of death. Subjects who are still alive at the time point of analyses, or who dropout prior to study end, will be censored at the day they were last known to be alive. If the sample is not enriched, the HR and 95% CI for treatment group will be estimated from a stratified Cox proportional hazards model overall and within randomization strata. In the case of enrichment, the HR and 95% CI for treatment group will be estimated from a Cox proportional hazards model including Merlin-negative subjects only. The adequacy of the model will be evaluated, including an assessment of the proportional hazards assumption. 2) Progression free survival For all subjects, PFS will be calculated from the date of randomization to the earliest date of CT scan with a central reading documenting relapse, | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Efficacy Endpoints: 1) Quality of Life using the Lung Cancer Symptom Scale (LCSS) modified for mesothelioma 2) Objective Response Rate Exploratory Endpoints: 1) Time to New Lesion 2) EQ-5D Health Assessment Questionnaire;Timepoint(s) of evaluation of this end point: Subjects will be treated until disease progression (as confirmed by central review) or other discontinuation criteria are met. Each subject’s active participation in this study will last a minimum of approximately 3.5 months, including: • Up to 28 day screening period. • At least 6 weeks of study treatment. However, subjects may continue to receive additional study treatment until disease progression has been documented or other discontinuation criteria have been met. • Follow-up visit performed 30 days after the last dose of study drug. Following documentation of non-death related progression, all subjects will be followed for survival by telephone contact every 2 months until death or the close of the study. | — |
Countries
Australia, Belgium, Canada, France, Italy, Japan, Netherlands, New Zealand, Norway, Poland, South Africa, Spain, Sweden, United Kingdom, United States
Contacts
Public ContactRegulatory Department
TMC Pharma Services Ltd
Outcome results
None listed