Placebo Controlled Study of VS-6063 in Subjects With Malignant Pleural Mesothelioma
Conditions
Malignant Pleural Mesothelioma
Conditions: official terms
Mesothelioma
Study Type
Interventional
Study Phase
Phase 2
Study Design
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment
Intervention
Name: defactinib (VS-6063) Type: Drug
Name: Placebo Type: Drug
Overall Status
Recruiting
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.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 18 Years
Gender: Both
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.
Locations
University of California San Francisco Medical Center
San Francisco, California, United States
Status: Recruiting
Contact: Scot Hammond - 415-885-3673 - HammondS@cc.ucsf.edu
University of Chicago Medical Center
Chicago, Illinois, United States
Status: Recruiting
Contact: Jennifer Hull, RN, OCN - 773-834-3137
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, United States
Status: Recruiting
Contact: Ronan Kelly - 443-287-0005
Mayo Clinic
Rochester, Minnesota, United States
Status: Recruiting
Contact: Mayo Clinic - 507-538-7623
Jacobi Medical Center
Bronx, New York, United States
Status: Recruiting
Contact: Claudia Calderon, RN - 718-918-3577
Roswell Park Cancer Institute
Buffalo, New York, United States
Status: Recruiting
Contact: Michelle Cooper - 716-845-4427 - Michele.Cooper@RoswellPark.org
Memorial Sloan Kettering Cancer Center
New York, New York, United States
Status: Recruiting
Contact: Dr. Marjorie Zauderer, MD - 646-888-4656
Cleveland Clinic
Cleveland, Ohio, United States
Status: Recruiting
Contact: Dr. James Stevenson, MD - 216-636-6888
Abramson Cancer Center
Philadelphia, Pennsylvania, United States
Status: Recruiting
Contact: Mona Jacobs-Small - 215-662-8632 - Mona.Jacobs-Small@uphs.upenn.edu
Sarah Cannon Research Institute
Nashville, Tennessee, United States
Status: Recruiting
Contact: Ask Sarah hotline - 877-691-7274
UT Southwestern
Dallas, Texas, United States
Status: Recruiting
Contact: Laurin Priddy - 214-648-1688
Peninsula Oncology Centre
Frankston, Victoria, Australia
Status: Recruiting
Contact: Albert Goikhman - 61 (0)3 9771 8910
Sir Charles Gairdner Hospital
Perth, Western Australia, Australia
Status: Recruiting
Contact: Judy Innes-Rowe - 08 63833280
Chris O'Brien Lifehouse at RPA
Camperdown, Australia
Status: Recruiting
Contact: Christine Merlino - +61 2 9515 7706
Epworth Hospital
Melbourne, Australia
Status: Recruiting
Contact: Felicity Osmond - +61 (3) 9936 8055
Northern Cancer Institute
Sydney, Australia
Status: Recruiting
Contact: Sally McCowatt - 02 9463 1181
Calvary Mater Newcastle
Waratah, Australia
Status: Recruiting
Contact: Fiona Abell - +61 (0)2 4014 3571
UCL - St. Luc
Brussel, Belgium
Status: Recruiting
Contact: Vanessa Erculisse - Vanessa.Erculisse@uclouvain.be
Antwerp University Hospital
Edegem, Belgium
Status: Recruiting
Contact: Ann Decoene - +32 3 8214719 - ann.decoene@uza.be
University Hopsital Ghent
Ghent, Belgium
Status: Recruiting
Contact: Veerle Surmont - veerle.surmont@uzgent.be
CHU Liege - Sart Tilman
Liege, Belgium
Status: Recruiting
Contact: Bernard Duysinx - bduysinx@chu.ulg.ac.be
Princess Margaret Hospital
Toronto, Ontario, Canada
Status: Recruiting
Contact: Andrea Foster - (416) 946-4501
CHRU, Lille
Lille, France
Status: Recruiting
Contact: Prof. Arnaud Scherpereel - 00 33 3 20 44 56 12
Hôpitaux de Marseille
Marseille, France
Status: Recruiting
Contact: Dr. Laurent Greillier - 00 33 4 91 96 59 01
Gustave Roussy
Villejuif, France
Status: Recruiting
Contact: Dr. Planchard - 00 33 1 42 11 45 64
Cliniche Humanitas Gavazzeni
Bergamo, Italy
Status: Recruiting
Contact: Giovanni Ceresoli - 0039 035 420 4663
Kyushu Cancer Center
Fukuoka, Japan
Status: Recruiting
Contact: Dr. Takashi Seto - 81925413231
Hiroshima University Hospital
Hiroshima, Japan
Status: Recruiting
Contact: Yoshihiro Miyata - 81-82-257-5869
Hyogo College of Medicine
Hyogo, Japan
Status: Recruiting
Contact: Dr. Taiichiro Otsuki - +81-798-45-6596
Okayama Rousai Hospital
Okayama, Japan
Status: Recruiting
Contact: Dr. Nobukazu Fujimoto - 81-86-262-0131
Kinki University Hospital
Osaka, Japan
Status: Recruiting
Contact: Dr. Toshio Shimizu - 81723-66-0221
Juntendo University
Tokyo, Japan
Status: Recruiting
Contact: Takehito Shukuya - +81358021589
Stichting Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis
Amsterdam, Netherlands
Status: Recruiting
Contact: Marianne Mahn - +31(0)205127496 - m.mahn@nki.nl
Medisch Spectrum Twente, Enschede
Enschede, Netherlands
Status: Recruiting
Contact: Ms. M. Mulder, MSc - +31 6 31 67 58 46 - M.Mulder@mst.nl
Atrium MC
Heerlen, Netherlands
Status: Recruiting
Contact: Carla Coenjaerd - 045-5766027 - c.coenjaerds@atriummc.nl
Atrium MC
Heerlen, Netherlands
Status: Recruiting
Contact: Carla Coenjaerds - 045-5766027 - c.coenjaerds@atriummc.nl
Erasmus MC
Rotterdam, Netherlands
Status: Recruiting
Contact: Mrs. A. L. Geel - +31 (0)107030323 - a.geel@erasmusmc.nl
Auckland Oncology Research Centre
Auckland, New Zealand
Status: Recruiting
Contact: Vivian Sun - Vsun@adhb.govt.nz
Canterbury Regional Cancer & Haematology Service
Christchurch, New Zealand
Status: Recruiting
Contact: Katie Moore - 6433641823
Norwegian Radium Hospital
Oslo, Norway
Status: Recruiting
Contact: Dr. Odd Terje Brustugun - ot.brustugun@gmail.com
The Medical Oncology Centre of Rosebank
Johannesburg, South Africa
Status: Recruiting
Contact: Teresa Smit - +27 11 880 4169
Mary Potter Oncology Center, Little Company of Mary Hospital
Pretoria, South Africa
Status: Recruiting
Contact: Marietjie Mouton - +27 12 346 6701
Institut Oncològic del Vallés Consorci Hospitalari Parc Tauli
Barcelona, Spain
Status: Recruiting
Contact: Jose Garcia Ruiz - +34 93 724 00 84
Vall d'Hebron University Hospital
Barcelona, Spain
Status: Recruiting
Contact: Marta Malo Perez - +34 93 274 60 00
Ensayos Clínicos Oncología
Madrid, Spain
Status: Recruiting
Contact: Dr. Santiago Ponce - +34 91 469 23 13
Hospital Madrid Norte- Sanchinarro, Centro Integral Oncológico Clara Campal (CIOCC)
Madrid, Spain
Status: Recruiting
Contact: Rocio Blanco - +34 91 756 79 84
Skane University Hospital
Lund, Sweden
Status: Recruiting
Contact: Dr. Ronny Ohman - : +46 (0)46 17 10 00
Karolinska University Hospital
Stockholm, Sweden
Status: Recruiting
Contact: Gunnar Hillerdal - +46 (0)8 517 700 00
University Hospital
Uppsala, Sweden
Status: Recruiting
Contact: Dr. Simon Ekman - +46 (0)18 611 00 00
Clatterbridge Cancer Centre
Bebington, Wirral, United Kingdom
Status: Recruiting
Contact: Laurie Lomax - 0151 482 7804 - Laurie.lomax@clatterbridgecc.nhs.uk
Southmead Hospital
Bristol, United Kingdom
Status: Recruiting
Contact: Deborah Warbrick - Deborah.Warbrick@nbt.nhs.uk
Addenbrooke's Hospital
Cambridge, United Kingdom
Status: Recruiting
Contact: Marian Coliof - +44 (0)1223 216083 - cctc@addenbrookes.nhs.uk
Velindre Hospital Cardiff
Cardiff, United Kingdom
Status: Recruiting
Contact: Amanda Jackson - +44 (0)2920 615888 - Amanda.Jackson2@wales.nhs.uk
Broomfield Hospital
Chelmsford, United Kingdom
Status: Recruiting
Contact: Lyndsay Johnson - 01254 516 339 - lyndsay.johnson@meht.nhs.uk
Tayside Cancer Centre
Dundee, United Kingdom
Status: Recruiting
Contact: Valerie Walker - Tascfeasibility.tayside@nhs.net
Beatson Oncology Centre
Glasgow, United Kingdom
Status: Recruiting
Contact: Julie Lang - julie.lang@ggc.scot.nhs.uk
Royal Surrey County Hospital
Guildford, United Kingdom
Status: Recruiting
Contact: Susanne Tluk, RN - 01483 571122 - s.tluk@nhs.net
Castle Hill Hospital
Hull, United Kingdom
Status: Recruiting
Contact: Karen Stubbs - karen.stubbs@hey.nhs.uk
Kent Oncology Centre, Maidstone Hospital
Kent, United Kingdom
Status: Recruiting
Contact: Karen McDonald - 01622 227093 - karenmcdonald@nhs.net
University of Leicester
Leicester, United Kingdom
Status: Recruiting
Contact: Anita Kang - +44 (0)116 258 7598 - Anita.Kang@uhl-tr.nhs.uk
Guys Hospital
London, United Kingdom
Status: Recruiting
Contact: Dr. James Spicer, MD - +44 (0) 207188 4260
St. Bartholomew's Hospital
London, United Kingdom
Status: Recruiting
Contact: Dr. Jeremy Steele - +44 7957645383 - Jeremy.steele@bartshealth.nhs.uk
Wythenshawe Hospital
Manchester, United Kingdom
Status: Recruiting
Contact: Dr. Paul Taylor - +44 (0)161 291 2829 - paul.taylor@uhsm.nhs.uk
Freeman Hospital
Newcastle, United Kingdom
Status: Recruiting
Contact: Chris Barron - 0191 213 8436 - chris.barron@nuth.nhs.uk
Derriford Hospital
Plymouth, United Kingdom
Status: Recruiting
Contact: Dr. Amy Roy - 01752 432335
Weston Park Hospital
Sheffield, United Kingdom
Status: Recruiting
Contact: Carol Crabtree - c.crabtree@sheffield.ac.uk
Southampton General Hospital
Southampton, United Kingdom
Status: Recruiting
Contact: Dr. Luke Nolan - +44 (0)23 8079 6802
Start Date
September 2013
Completion Date
December 2016
Sponsors
Verastem, Inc.
Source
Verastem, Inc.
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page