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

NCT01870609 | Terminated Phase 2 DMC

• 1 other identifier: VS-6063-202
• Study Type: interventional
• Target: 344
• Locations: 15 countries
• Sites: 73

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

Outcome Measures

Primary Outcomes (2)

• Compare the overall survival (OS) in subjects with malignant pleural mesothelioma receiving defactinib (VS-6063) or placebo

  The median duration of OS will be estimated based on the 50th percentile of the Kaplan-Meier distribution

  From randomization to end of life, an expected average of 12 months

• Compare the progression free survival (PFS) in subjects with malignant pleural mesothelioma receiving defactinib (VS-6063) or placebo

  PFS will be calculated based on the stratified log-rank test, and will use Kaplan-Meier estimation methods for estimation of summary statistics

  From date of randomization to earliest documented date of progression, an expected average of 4 months

Secondary Outcomes (2)

• To assess Quality of Life (QoL) in subjects treated with defactinib (VS-6063) or placebo using the Lung Cancer Symptom Scale modified for mesothelioma (LCSS-Meso)

  Every 3-4 weeks from baseline through end of treatment, an expected average of 4 months

• To determine the objective response rate (ORR) in subjects receiving defactinib (VS-6063) or placebo.

  Every 6-8 weeks from baseline through end of treatment, an expected average of 4 months

Other Outcomes (5)

• Determine the time to new lesion in subjects receiving defactinib (VS-6063) or placebo

  Every 6-8 weeks from baseline until end of treatment, an expected average of 4 months

• Evaluate the relationship of defactinib (VS-6063) pharmacokinetics (PK) and outcome

  Time points at Week 4, Week 7, Week 10 and Week 13

• Evaluate the population pharmacokinetics of defactinib (VS-6063) in subjects with malignant pleural mesothelioma

  Time points at Week 4, Week 7, Week 10 and Week 13

Study Arms (2)

defactinib (VS-6063)

ACTIVE COMPARATOR

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

Drug: defactinib (VS-6063)

Placebo

PLACEBO COMPARATOR

2 placebo tablets, administered orally, twice daily

Drug: Placebo

Interventions

defactinib (VS-6063) DRUG

defactinib (VS-6063)

Placebo DRUG

Sugar pill manufactured to mimic defactinib tablet

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Able to understand and give written informed consent and comply with study procedures.
• \. 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.
• \. Evaluable disease, or measurable disease as assessed by RECIST version 1.1.
• \. 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.
• \. Received last dose of prior chemotherapy within ≤ 6 weeks of first dose of VS-6063.
• \. Have completed baseline quality of life evaluation as assessed by LCSS modified for mesothelioma
• \. Age ≥18 years.
• \. Life expectancy ≥3 months.
• \. All prior cytotoxic toxicities must have resolved to grade ≤ 1 prior to randomization.
• \. Performance status according to the Karnofsky Scale of ≥ 70% (after palliative measures such as pleural drainage).
• \. Corrected QT interval (QTc) \< 470 ms (as calculated by the Fridericia correction formula).
• \. 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.
• \. Adequate renal function (creatinine ≤ 1.5 x ULN \[upper limit of normal\] or glomerular filtration rate of ≥ 50mL/min).
• \. Adequate hepatic function (total bilirubin ≤ 1.5 x ULN for the institution; aspartate transaminase \[AST\] and alanine transaminase \[ALT\] ≤ 2.5 x ULN).
• \. 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.

You may not qualify if:

• \. Currently enrolled in (or completed within 30 days before study drug administration)another investigational drug study.
• \. GI condition that could interfere with the swallowing or absorption of study drug.
• \. History of upper GI bleeding, ulceration, or perforation within 12 months prior to the first dose of study drug.
• \. Known history of Gilbert's Syndrome.
• \. Known history of stroke or cerebrovascular accident within 6 months prior to the first dose of study drug.
• \. Subjects with known infection with human immunodeficiency virus or Acquired Immune Deficiency Syndrome (testing not required).
• \. Subjects with known infection with hepatitis A, B or C (testing not required).
• \. Any evidence of serious active infections.
• \. Major surgery within 28 days prior to the first dose of study drug.
• \. 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.
• \. 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.
• Known history of malignant hypertension.
• \. Psychiatric illness or social situations that would limit compliance with study requirements.
• \. 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.
• \. Prior treatment with drugs an FAK inhibitor.

Sponsors & Collaborators

• Verastem, Inc.: lead

Study Sites (73)

University of California San Francisco Medical Center

San Francisco, California, United States

Location

Cleveland Clinic Florida

Weston, Florida, 33331, United States

Location

University of Chicago Medical Center

Chicago, Illinois, United States

Location

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, United States

Location

Mayo Clinic

Rochester, Minnesota, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Jacobi Medical Center

The Bronx, New York, 10461, United States

Location

Cleveland Clinic

Cleveland, Ohio, United States

Location

Abramson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, United States

Location

UT Southwestern

Dallas, Texas, United States

Location

Peninsula Oncology Centre

Frankston, Victoria, Australia

Location

Sir Charles Gairdner Hospital

Perth, Western Australia, Australia

Location

Chris O'Brien Lifehouse at RPA

Camperdown, Australia

Location

Monash Cancer Center

East Bentlrigh, 3165, Australia

Location

Epworth Hospital

Melbourne, Australia

Location

Northern Cancer Institute

Sydney, Australia

Location

Calvary Mater Newcastle

Waratah, Australia

Location

Princess Alexandra Hospital +61(0)7 3176 5054

Woolloongabba, QLD 4102, Australia

Location

UCL - St. Luc

Brussels, Belgium

Location

Antwerp University Hospital

Edegem, Belgium

Location

University Hopsital Ghent

Ghent, Belgium

Location

Universitaire Ziekenhuizen Leuven (University Hospitals Leuven)

Leuven, Belgium

Location

CHU Liege - Sart Tilman

Liège, Belgium

Location

Princess Margaret Hospital

Toronto, Ontario, Canada

Location

CHRU, Lille

Lille, France

Location

Hôpitaux de Marseille

Marseille, France

Location

Gustave Roussy

Villejuif, France

Location

Cliniche Humanitas Gavazzeni

Bergamo, Italy

Location

Istituto Oncologico Veneto

Padua, Italy

Location

Kyushu Cancer Center

Fukuoka, Japan

Location

Hiroshima University Hospital

Hiroshima, Japan

Location

Hyogo College of Medicine

Hyōgo, Japan

Location

Okayama Rousai Hospital

Okayama, Japan

Location

Kinki University Hospital

Osaka, Japan

Location

Juntendo University

Tokyo, Japan

Location

Stichting Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis

Amsterdam, Netherlands

Location

Medisch Spectrum Twente, Enschede

Enschede, Netherlands

Location

Atrium MC

Heerlen, Netherlands

Location

Erasmus MC

Rotterdam, Netherlands

Location

Auckland Oncology Research Centre

Auckland, New Zealand

Location

Canterbury Regional Cancer & Haematology Service

Christchurch, New Zealand

Location

Norwegian Radium Hospital

Oslo, Norway

Location

Centrum Pulmonologii Ii Torakochirurgii w Bystrej

Bystra, Poland

Location

Iatros International / Bloemfontein Medi-Clinic

Bloemfontein, Free State, South Africa

Location

The Medical Oncology Centre of Rosebank

Johannesburg, South Africa

Location

Mary Potter Oncology Center, Little Company of Mary Hospital

Pretoria, South Africa

Location

Institut Oncològic del Vallés Consorci Hospitalari Parc Tauli

Barcelona, Spain

Location

Vall d'Hebron University Hospital

Barcelona, Spain

Location

Ensayos Clínicos Oncología

Madrid, Spain

Location

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

Madrid, Spain

Location

Skane University Hospital

Lund, Sweden

Location

Karolinska University Hospital

Stockholm, Sweden

Location

University Hospital

Uppsala, Sweden

Location

Clatterbridge Cancer Centre

Bebington, Wirral, United Kingdom

Location

Southmead Hospital

Bristol, United Kingdom

Location

Addenbrooke's Hospital

Cambridge, United Kingdom

Location

Velindre Hospital Cardiff

Cardiff, United Kingdom

Location

Broomfield Hospital

Chelmsford, CM1 7ET, United Kingdom

Location

Tayside Cancer Centre

Dundee, United Kingdom

Location

Beatson Oncology Centre

Glasgow, United Kingdom

Location

Royal Surrey County Hospital

Guildford, United Kingdom

Location

Castle Hill Hospital

Hull, United Kingdom

Location

Kent Oncology Centre, Maidstone Hospital

Kent, United Kingdom

Location

University of Leicester

Leicester, United Kingdom

Location

Guys Hospital

London, United Kingdom

Location

St. Bartholomew's Hospital

London, United Kingdom

Location

Wythenshawe Hospital

Manchester, United Kingdom

Location

Freeman Hospital

Newcastle, United Kingdom

Location

Derriford Hospital

Plymouth, United Kingdom

Location

Weston Park Hospital

Sheffield, S10 2SJ, United Kingdom

Location

Southampton General Hospital

Southampton, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 30785827 DERIVED

MeSH Terms

Conditions

Mesothelioma, Malignant

Interventions

defactinib

Condition Hierarchy (Ancestors)

Mesothelioma; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Pleural Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Hagop Youssoufian

  Verastem, Inc.

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 29, 2013
• First Posted: June 6, 2013
• Study Start: September 1, 2013
• Primary Completion: January 1, 2016
• Study Completion: January 1, 2016
• Last Updated: January 30, 2017

Record last verified: 2016-03

Locations

IT (2); GB (18); ES (4); JP (6); ZA (3); CA (1); US (12); NL (4); NZ (2); AU (8); PL (1); SE (3); FR (3); BE (5); NO (1)