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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01870609




Registration number
NCT01870609
Ethics application status
Date submitted
29/05/2013
Date registered
6/06/2013
Date last updated
30/01/2017

Titles & IDs
Public title
Placebo Controlled Study of VS-6063 in Subjects With Malignant Pleural Mesothelioma
Scientific title
A Phase 2 Randomized, Double-Blind, Placebo-Controlled, Multicenter Study of VS-6063 in Subjects With Malignant Pleural Mesothelioma
Secondary ID [1] 0 0
VS-6063-202
Universal Trial Number (UTN)
Trial acronym
COMMAND
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Malignant Pleural Mesothelioma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - defactinib (VS-6063)
Treatment: Drugs - Placebo

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

Placebo Comparator: Placebo - 2 placebo tablets, administered orally, twice daily


Treatment: Drugs: defactinib (VS-6063)


Treatment: Drugs: Placebo
Sugar pill manufactured to mimic defactinib tablet
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Compare the overall survival (OS) in subjects with malignant pleural mesothelioma receiving defactinib (VS-6063) or placebo
Timepoint [1] 0 0
From randomization to end of life, an expected average of 12 months
Primary outcome [2] 0 0
Compare the progression free survival (PFS) in subjects with malignant pleural mesothelioma receiving defactinib (VS-6063) or placebo
Timepoint [2] 0 0
From date of randomization to earliest documented date of progression, an expected average of 4 months
Secondary outcome [1] 0 0
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)
Timepoint [1] 0 0
Every 3-4 weeks from baseline through end of treatment, an expected average of 4 months
Secondary outcome [2] 0 0
To determine the objective response rate (ORR) in subjects receiving defactinib (VS-6063) or placebo.
Timepoint [2] 0 0
Every 6-8 weeks from baseline through end of treatment, an expected average of 4 months

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/09/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/01/2016
Sample size
Target
Accrual to date
Final
344
Recruitment in Australia
Recruitment state(s)
VIC,WA
Recruitment hospital [1] 0 0
Peninsula Oncology Centre - Frankston
Recruitment hospital [2] 0 0
Sir Charles Gairdner Hospital - Perth
Recruitment hospital [3] 0 0
Chris O'Brien Lifehouse at RPA - Camperdown
Recruitment hospital [4] 0 0
Monash Cancer Center - East Bentlrigh
Recruitment hospital [5] 0 0
Epworth Hospital - Melbourne
Recruitment hospital [6] 0 0
Northern Cancer Institute - Sydney
Recruitment hospital [7] 0 0
Calvary Mater Newcastle - Waratah
Recruitment hospital [8] 0 0
Princess Alexandra Hospital +61(0)7 3176 5054 - Woolloongabba
Recruitment postcode(s) [1] 0 0
- Frankston
Recruitment postcode(s) [2] 0 0
- Perth
Recruitment postcode(s) [3] 0 0
- Camperdown
Recruitment postcode(s) [4] 0 0
3165 - East Bentlrigh
Recruitment postcode(s) [5] 0 0
- Melbourne
Recruitment postcode(s) [6] 0 0
- Sydney
Recruitment postcode(s) [7] 0 0
- Waratah
Recruitment postcode(s) [8] 0 0
QLD 4102 - Woolloongabba
Recruitment outside Australia
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United States of America
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California
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Florida
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Illinois
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Maryland
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Ohio
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Pennsylvania
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Tennessee
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Texas
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Belgium
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Brussel
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Belgium
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Edegem
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Belgium
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Ghent
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Belgium
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Leuven
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Belgium
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Liege
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Canada
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Ontario
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France
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Lille
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France
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Marseille
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France
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Villejuif
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Bergamo
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Padova
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Fukuoka
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Hyogo
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Okayama
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Osaka
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Tokyo
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Amsterdam
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Enschede
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Heerlen
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Rotterdam
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Auckland
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Christchurch
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Oslo
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Poland
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Bystra
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Free State
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South Africa
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Johannesburg
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Pretoria
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Barcelona
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Lund
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Sweden
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Stockholm
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Sweden
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Uppsala
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United Kingdom
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Wirral
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Bristol
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Cambridge
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Cardiff
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Chelmsford
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Dundee
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Glasgow
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Guildford
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Hull
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Kent
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Leicester
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London
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Manchester
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Newcastle
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Plymouth
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Sheffield
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United Kingdom
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Southampton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Verastem, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01870609
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Hagop Youssoufian
Address 0 0
Verastem, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01870609