Placebo Controlled Study of VS-6063 in Subjects With Malignant Pleural Mesothelioma

NCT ID: NCT01870609

Last Updated: 2017-01-30

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 344 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-09-30
• Study Completion Date: 2016-01-31

Brief Summary

This study is a Phase 2, randomized, double-blind, placebo-controlled, multicenter study of defactinib (VS-6063) in subjects with malignant pleural mesothelioma (MPM) who have not progressed (confirmed partial response or stable disease) following ≥ 4 cycles of treatment with pemetrexed/cisplatin or pemetrexed/carboplatin. Prior to entry and randomization to the study, each subject must have tumor Merlin status(high or low) established by immunohistochemistry performed at a central laboratory. Subjects will be randomized in a 1:1 ratio to receive oral VS-6063 400 mg twice per day, or matched placebo. Randomization will be stratified by tumor Merlin status (high versus low). Progression will be assessed both locally and by central review using the Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1. Subjects will continue to receive treatment until disease progression or other discontinuation criteria are met. Following documentation of nonfatal disease progression, all subjects will be followed for overall survival by telephone contact every 2 months until end of life or the close of the study.

Conditions

Malignant Pleural Mesothelioma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

defactinib (VS-6063)

2 x 200 mg defactinib (VS-6063) tablets, administered orally, twice daily

Group Type: ACTIVE_COMPARATOR

defactinib (VS-6063)

Intervention Type: DRUG

Placebo

2 placebo tablets, administered orally, twice daily

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Sugar pill manufactured to mimic defactinib tablet

Interventions

defactinib (VS-6063)

Intervention Type: DRUG

Placebo

Sugar pill manufactured to mimic defactinib tablet

Intervention Type: DRUG

Eligibility 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.
• 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 cytotoxic toxicities must have resolved to grade ≤ 1 prior to randomization.
• 10. Performance status according to the Karnofsky Scale of ≥ 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 [ANC] ≥ 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] or glomerular filtration rate of ≥ 50mL/min).
• 14. Adequate hepatic function (total bilirubin ≤ 1.5 x ULN for the institution; aspartate transaminase [AST] and alanine transaminase [ALT] ≤ 2.5 x 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.

Exclusion Criteria

• 1. Currently enrolled in (or completed within 30 days before study drug administration)another investigational drug study.
• 2. 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 (testing not required).
• 7. Subjects with known infection with hepatitis A, B or C (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 previously 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 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 noninvasive,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 drugs an FAK inhibitor.
• 16. Women who are pregnant or breastfeeding.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Verastem, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Hagop Youssoufian

Role: STUDY_CHAIR

Verastem, Inc.

Locations

University of California San Francisco Medical Center

San Francisco, California, United States

Cleveland Clinic Florida

Weston, Florida, United States

University of Chicago Medical Center

Chicago, Illinois, United States

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, United States

Mayo Clinic

Rochester, Minnesota, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Jacobi Medical Center

The Bronx, New York, United States

Cleveland Clinic

Cleveland, Ohio, United States

Abramson Cancer Center

Philadelphia, Pennsylvania, United States

Sarah Cannon Research Institute

Nashville, Tennessee, United States

UT Southwestern

Dallas, Texas, United States

Peninsula Oncology Centre

Frankston, Victoria, Australia

Sir Charles Gairdner Hospital

Perth, Western Australia, Australia

Chris O'Brien Lifehouse at RPA

Camperdown, , Australia

Monash Cancer Center

East Bentlrigh, , Australia

Epworth Hospital

Melbourne, , Australia

Northern Cancer Institute

Sydney, , Australia

Calvary Mater Newcastle

Waratah, , Australia

Princess Alexandra Hospital +61(0)7 3176 5054

Woolloongabba, , Australia

UCL - St. Luc

Brussels, , Belgium

Antwerp University Hospital

Edegem, , Belgium

University Hopsital Ghent

Ghent, , Belgium

Universitaire Ziekenhuizen Leuven (University Hospitals Leuven)

Leuven, , Belgium

CHU Liege - Sart Tilman

Liège, , Belgium

Princess Margaret Hospital

Toronto, Ontario, Canada

CHRU, Lille

Lille, , France

Hôpitaux de Marseille

Marseille, , France

Gustave Roussy

Villejuif, , France

Cliniche Humanitas Gavazzeni

Bergamo, , Italy

Istituto Oncologico Veneto

Padua, , Italy

Kyushu Cancer Center

Fukuoka, , Japan

Hiroshima University Hospital

Hiroshima, , Japan

Hyogo College of Medicine

Hyōgo, , Japan

Okayama Rousai Hospital

Okayama, , Japan

Kinki University Hospital

Osaka, , Japan

Juntendo University

Tokyo, , Japan

Stichting Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis

Amsterdam, , Netherlands

Medisch Spectrum Twente, Enschede

Enschede, , Netherlands

Atrium MC

Heerlen, , Netherlands

Erasmus MC

Rotterdam, , Netherlands

Auckland Oncology Research Centre

Auckland, , New Zealand

Canterbury Regional Cancer & Haematology Service

Christchurch, , New Zealand

Norwegian Radium Hospital

Oslo, , Norway

Centrum Pulmonologii Ii Torakochirurgii w Bystrej

Bystra, , Poland

Iatros International / Bloemfontein Medi-Clinic

Bloemfontein, Free State, South Africa

The Medical Oncology Centre of Rosebank

Johannesburg, , South Africa

Mary Potter Oncology Center, Little Company of Mary Hospital

Pretoria, , South Africa

Institut Oncològic del Vallés Consorci Hospitalari Parc Tauli

Barcelona, , Spain

Vall d'Hebron University Hospital

Barcelona, , Spain

Ensayos Clínicos Oncología

Madrid, , Spain

Hospital Madrid Norte- Sanchinarro, Centro Integral Oncológico Clara Campal (CIOCC)

Madrid, , Spain

Skane University Hospital

Lund, , Sweden

Karolinska University Hospital

Stockholm, , Sweden

University Hospital

Uppsala, , Sweden

Clatterbridge Cancer Centre

Bebington, Wirral, United Kingdom

Southmead Hospital

Bristol, , United Kingdom

Addenbrooke's Hospital

Cambridge, , United Kingdom

Velindre Hospital Cardiff

Cardiff, , United Kingdom

Broomfield Hospital

Chelmsford, , United Kingdom

Tayside Cancer Centre

Dundee, , United Kingdom

Beatson Oncology Centre

Glasgow, , United Kingdom

Royal Surrey County Hospital

Guildford, , United Kingdom

Castle Hill Hospital

Hull, , United Kingdom

Kent Oncology Centre, Maidstone Hospital

Kent, , United Kingdom

University of Leicester

Leicester, , United Kingdom

Guys Hospital

London, , United Kingdom

St. Bartholomew's Hospital

London, , United Kingdom

Wythenshawe Hospital

Manchester, , United Kingdom

Freeman Hospital

Newcastle, , United Kingdom

Derriford Hospital

Plymouth, , United Kingdom

Weston Park Hospital

Sheffield, , United Kingdom

Southampton General Hospital

Southampton, , United Kingdom

Countries

United States; Australia; Belgium; Canada; France; Italy; Japan; Netherlands; New Zealand; Norway; Poland; South Africa; Spain; Sweden; United Kingdom

References

Fennell DA, Baas P, Taylor P, Nowak AK, Gilligan D, Nakano T, Pachter JA, Weaver DT, Scherpereel A, Pavlakis N, van Meerbeeck JP, Cedres S, Nolan L, Kindler H, Aerts JGJV. Maintenance Defactinib Versus Placebo After First-Line Chemotherapy in Patients With Merlin-Stratified Pleural Mesothelioma: COMMAND-A Double-Blind, Randomized, Phase II Study. J Clin Oncol. 2019 Apr 1;37(10):790-798. doi: 10.1200/JCO.2018.79.0543. Epub 2019 Feb 20.

Reference Type: DERIVED

PMID: 30785827 (View on PubMed)

Other Identifiers

VS-6063-202

Identifier Type: -

Identifier Source: org_study_id