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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01870609
Recruitment Status : Terminated (Interim analysis-DSMB stated good safety profile but lack of efficacy)
First Posted : June 6, 2013
Last Update Posted : January 30, 2017
Information provided by (Responsible Party):
Verastem, Inc.

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.

Condition or disease Intervention/treatment Phase
Malignant Pleural Mesothelioma Drug: defactinib (VS-6063) Drug: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 344 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 2 Randomized, Double-Blind, Placebo-Controlled, Multicenter Study of VS-6063 in Subjects With Malignant Pleural Mesothelioma
Study Start Date : September 2013
Actual Primary Completion Date : January 2016
Actual Study Completion Date : January 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Mesothelioma

Arm Intervention/treatment
Active Comparator: defactinib (VS-6063)
2 x 200 mg defactinib (VS-6063) tablets, administered orally, twice daily
Drug: defactinib (VS-6063)
Placebo Comparator: Placebo
2 placebo tablets, administered orally, twice daily
Drug: Placebo
Sugar pill manufactured to mimic defactinib tablet

Primary Outcome Measures :
  1. Compare the overall survival (OS) in subjects with malignant pleural mesothelioma receiving defactinib (VS-6063) or placebo [ Time Frame: From randomization to end of life, an expected average of 12 months ]
    The median duration of OS will be estimated based on the 50th percentile of the Kaplan-Meier distribution

  2. Compare the progression free survival (PFS) in subjects with malignant pleural mesothelioma receiving defactinib (VS-6063) or placebo [ Time Frame: From date of randomization to earliest documented date of progression, an expected average of 4 months ]
    PFS will be calculated based on the stratified log-rank test, and will use Kaplan-Meier estimation methods for estimation of summary statistics

Secondary Outcome Measures :
  1. 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) [ Time Frame: Every 3-4 weeks from baseline through end of treatment, an expected average of 4 months ]
    QoL will be assessed using the LCSS-Meso. The LCSS-Meso total score will be analyzed through a comparison of median area under the curve (AUC) between the 2 treatment groups using a Wilcoxon test.

  2. To determine the objective response rate (ORR) in subjects receiving defactinib (VS-6063) or placebo. [ Time Frame: Every 6-8 weeks from baseline through end of treatment, an expected average of 4 months ]
    ORR is measured as the best overall response assessed by central review using Response Evaluation Criteria In Solid Tumors (RECIST), version 1.1.

Other Outcome Measures:
  1. Determine the time to new lesion in subjects receiving defactinib (VS-6063) or placebo [ Time Frame: Every 6-8 weeks from baseline until end of treatment, an expected average of 4 months ]
    Time to new lesion will be calculated from the date of randomization to the time of CT scan documenting a new lesion or date of other unambiguous indicator of new lesion development.

  2. Evaluate the relationship of defactinib (VS-6063) pharmacokinetics (PK) and outcome [ Time Frame: Time points at Week 4, Week 7, Week 10 and Week 13 ]
    PK parameters, including but not limited to plasma concentration, AUC (Area Under Curve) 0-t, Cmax, Tmax, and T1/2, compared with outcome

  3. Evaluate the population pharmacokinetics of defactinib (VS-6063) in subjects with malignant pleural mesothelioma [ Time Frame: Time points at Week 4, Week 7, Week 10 and Week 13 ]
    PK parameters, including but not limited to plasma concentration, AUC (Area Under Curve) 0-t, Cmax, Tmax, and T1/2

  4. Evaluate the safety and tolerability of defactinib (VS-6063) in subjects with malignant pleural mesothelioma [ Time Frame: From start of treatment to end of treatment, an expected average of 4 months ]
    Adverse events and their frequency, duration and severity, physical examination, laboratory parameters, vital signs and ECG change monitoring as determined based on CTCAE (Common Toxicity Criteria for Adverse Effects) 4.03

  5. To collect EuroQol 5-Dimensional Health Questionnaire (EQ-5D) for health economics purposes [ Time Frame: Every 3-4 weeks from baseline through end of treatment, an expected average of 4 months ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01870609

Hide Hide 73 study locations
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United States, California
University of California San Francisco Medical Center
San Francisco, California, United States
United States, Florida
Cleveland Clinic Florida
Weston, Florida, United States, 33331
United States, Illinois
University of Chicago Medical Center
Chicago, Illinois, United States
United States, Maryland
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, United States
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States
United States, New York
Jacobi Medical Center
Bronx, New York, United States, 10461
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
United States, Ohio
Cleveland Clinic
Cleveland, Ohio, United States
United States, Pennsylvania
Abramson Cancer Center
Philadelphia, Pennsylvania, United States, 19104
United States, Tennessee
Sarah Cannon Research Institute
Nashville, Tennessee, United States
United States, Texas
UT Southwestern
Dallas, Texas, United States
Australia, Victoria
Peninsula Oncology Centre
Frankston, Victoria, Australia
Australia, Western Australia
Sir Charles Gairdner Hospital
Perth, Western Australia, Australia
Chris O'Brien Lifehouse at RPA
Camperdown, Australia
Monash Cancer Center
East Bentlrigh, Australia, 3165
Epworth Hospital
Melbourne, Australia
Northern Cancer Institute
Sydney, Australia
Calvary Mater Newcastle
Waratah, Australia
Princess Alexandra Hospital +61(0)7 3176 5054
Woolloongabba, Australia, QLD 4102
UCL - St. Luc
Brussel, Belgium
Antwerp University Hospital
Edegem, Belgium
University Hopsital Ghent
Ghent, Belgium
Universitaire Ziekenhuizen Leuven (University Hospitals Leuven)
Leuven, Belgium
CHU Liege - Sart Tilman
Liege, Belgium
Canada, Ontario
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
Padova, Italy
Kyushu Cancer Center
Fukuoka, Japan
Hiroshima University Hospital
Hiroshima, Japan
Hyogo College of Medicine
Hyogo, 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
New Zealand
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
South Africa
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
United Kingdom
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, CM1 7ET
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, S10 2SJ
Southampton General Hospital
Southampton, United Kingdom
Sponsors and Collaborators
Verastem, Inc.
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Study Chair: Hagop Youssoufian Verastem, Inc.
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Verastem, Inc. Identifier: NCT01870609    
Other Study ID Numbers: VS-6063-202
First Posted: June 6, 2013    Key Record Dates
Last Update Posted: January 30, 2017
Last Verified: March 2016
Additional relevant MeSH terms:
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Mesothelioma, Malignant
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Mesothelial
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Pleural Neoplasms
Lung Diseases
Respiratory Tract Diseases