AzTrials
AzTrials

Malignant Pleural MesotheliomaPhase 2COMMANDNCT01870609

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

A Phase 2 study testing defactinib (VS-6063) in people with Malignant Pleural Mesothelioma, run by Verastem, Inc. at 73 sites in 15 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Malignant Pleural Mesothelioma
What is being tested?
defactinib (VS-6063)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
344 participants
Where
73 sitesin 15 countries
Study dates
Sep 2013to Jan 2016
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 15Show fewer
  • 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.

Who cannot join

  • 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).
Show all 16Show fewer
  • 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.

Trial locations and contacts

73 sites in 15 countries.

73 sites in 15 countries

United Kingdom18 sites

  • Clatterbridge Cancer Centre

    Bebington, Wirral

  • Southmead Hospital

    Bristol

  • Addenbrooke's Hospital

    Cambridge

  • Velindre Hospital Cardiff

    Cardiff

  • Broomfield Hospital

    Chelmsford, CM1 7ET

  • Tayside Cancer Centre

    Dundee

  • Beatson Oncology Centre

    Glasgow

  • Royal Surrey County Hospital

    Guildford

  • Castle Hill Hospital

    Hull

  • Kent Oncology Centre, Maidstone Hospital

    Kent

  • University of Leicester

    Leicester

  • Guys Hospital

    London

  • St. Bartholomew's Hospital

    London

  • Wythenshawe Hospital

    Manchester

  • Freeman Hospital

    Newcastle

  • Derriford Hospital

    Plymouth

  • Weston Park Hospital

    Sheffield, S10 2SJ

  • Southampton General Hospital

    Southampton

Other trials in United Kingdom

United States12 sites

  • Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

    Baltimore, Maryland

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

  • University of Chicago Medical Center

    Chicago, Illinois

  • Cleveland Clinic

    Cleveland, Ohio

  • UT Southwestern

    Dallas, Texas

  • Sarah Cannon Research Institute

    Nashville, Tennessee

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Abramson Cancer Center

    Philadelphia, Pennsylvania, 19104

  • Mayo Clinic

    Rochester, Minnesota

  • University of California San Francisco Medical Center

    San Francisco, California

  • Jacobi Medical Center

    The Bronx, New York, 10461

  • Cleveland Clinic Florida

    Weston, Florida, 33331

Other trials in United States

Australia8 sites

  • Chris O'Brien Lifehouse at RPA

    Camperdown

  • Monash Cancer Center

    East Bentlrigh, 3165

  • Peninsula Oncology Centre

    Frankston, Victoria

  • Epworth Hospital

    Melbourne

  • Sir Charles Gairdner Hospital

    Perth, Western Australia

  • Northern Cancer Institute

    Sydney

  • Calvary Mater Newcastle

    Waratah

  • Princess Alexandra Hospital +61(0)7 3176 5054

    Woolloongabba, QLD 4102

Other trials in Australia

Japan6 sites

  • Kyushu Cancer Center

    Fukuoka

  • Hiroshima University Hospital

    Hiroshima

  • Hyogo College of Medicine

    Hyōgo

  • Okayama Rousai Hospital

    Okayama

  • Kinki University Hospital

    Osaka

  • Juntendo University

    Tokyo

Other trials in Japan

Belgium5 sites

  • UCL - St. Luc

    Brussels

  • Antwerp University Hospital

    Edegem

  • University Hopsital Ghent

    Ghent

  • Universitaire Ziekenhuizen Leuven (University Hospitals Leuven)

    Leuven

  • CHU Liege - Sart Tilman

    Liège

Other trials in Belgium

Netherlands4 sites

  • Stichting Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis

    Amsterdam

  • Medisch Spectrum Twente, Enschede

    Enschede

  • Atrium MC

    Heerlen

  • Erasmus MC

    Rotterdam

Other trials in Netherlands

Spain4 sites

  • Institut Oncològic del Vallés Consorci Hospitalari Parc Tauli

    Barcelona

  • Vall d'Hebron University Hospital

    Barcelona

  • Ensayos Clínicos Oncología

    Madrid

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

    Madrid

Other trials in Spain

France3 sites

  • CHRU, Lille

    Lille

  • Hôpitaux de Marseille

    Marseille

  • Gustave Roussy

    Villejuif

Other trials in France

South Africa3 sites

  • Iatros International / Bloemfontein Medi-Clinic

    Bloemfontein, Free State

  • The Medical Oncology Centre of Rosebank

    Johannesburg

  • Mary Potter Oncology Center, Little Company of Mary Hospital

    Pretoria

Other trials in South Africa

Sweden3 sites

  • Skane University Hospital

    Lund

  • Karolinska University Hospital

    Stockholm

  • University Hospital

    Uppsala

Other trials in Sweden

Italy2 sites

  • Cliniche Humanitas Gavazzeni

    Bergamo

  • Istituto Oncologico Veneto

    Padova

Other trials in Italy

New Zealand2 sites

  • Auckland Oncology Research Centre

    Auckland

  • Canterbury Regional Cancer & Haematology Service

    Christchurch

Other trials in New Zealand

Canada1 site

  • Princess Margaret Hospital

    Toronto, Ontario

Other trials in Canada

Norway1 site

  • Norwegian Radium Hospital

    Oslo

Other trials in Norway

Poland1 site

  • Centrum Pulmonologii Ii Torakochirurgii w Bystrej

    Bystra

Other trials in Poland

About this study

Official title: A Phase 2 Randomized, Double-Blind, Placebo-Controlled, Multicenter Study of VS-6063 in Subjects With Malignant Pleural Mesothelioma

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.

Being tested
defactinib (VS-6063), Placebo
Medical subject headings
Mesothelioma, Malignant

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • defactinib (VS-6063)Drug

  • PlaceboDrug

    Sugar pill manufactured to mimic defactinib tablet

Study groups in NCT01870609
Study groupRoleWhat they receive
defactinib (VS-6063)Active comparator2 x 200 mg defactinib (VS-6063) tablets, administered orally, twice daily
Receives: Drug: defactinib (VS-6063)
PlaceboPlacebo comparator2 placebo tablets, administered orally, twice daily
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

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

  2. 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

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

Secondary outcomes (2)

  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)

    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.

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

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

    ORR is measured as the best overall response assessed by central review using Response Evaluation Criteria In Solid Tumors (RECIST), version 1.1.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Jun 2013 (estimated)
  2. Study startSep 2013
  3. Primary completionJan 2016
  4. Study completionJan 2016

Why it stopped: Interim analysis-DSMB stated good safety profile but lack of efficacy

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
344 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01870609
Sponsor's protocol ID
VS-6063-202
Acronym
COMMAND
Status last verified
Mar 2016
First submitted
29 May 2013
Last updated
30 Jan 2017
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 30785827

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing defactinib (VS-6063) in people with Malignant Pleural Mesothelioma, run by Verastem, Inc. at 73 sites in 15 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 30 Jan 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 73 sites in United Kingdom, United States, Australia, Japan, Belgium and 10 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Interim analysis-DSMB stated good safety profile but lack of efficacy). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01870609, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jan 2017.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in