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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.
- 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
University of Chicago Medical Center
Status: Recruiting
Contact: Scot Hammond - 415-885-3673 - HammondS@cc.ucsf.edu
Chicago, Illinois, United States
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
Status: Recruiting
Contact: Jennifer Hull, RN, OCN - 773-834-3137
Baltimore, Maryland, United States
Mayo Clinic
Status: Recruiting
Contact: Ronan Kelly - 443-287-0005
Rochester, Minnesota, United States
Jacobi Medical Center
Status: Recruiting
Contact: Mayo Clinic - 507-538-7623
Bronx, New York, United States
Roswell Park Cancer Institute
Status: Recruiting
Contact: Claudia Calderon, RN - 718-918-3577
Buffalo, New York, United States
Memorial Sloan Kettering Cancer Center
Status: Recruiting
Contact: Michelle Cooper - 716-845-4427 - Michele.Cooper@RoswellPark.org
New York, New York, United States
Cleveland Clinic
Status: Recruiting
Contact: Dr. Marjorie Zauderer, MD - 646-888-4656
Cleveland, Ohio, United States
Abramson Cancer Center
Status: Recruiting
Contact: Dr. James Stevenson, MD - 216-636-6888
Philadelphia, Pennsylvania, United States
Sarah Cannon Research Institute
Status: Recruiting
Contact: Mona Jacobs-Small - 215-662-8632 - Mona.Jacobs-Small@uphs.upenn.edu
Nashville, Tennessee, United States
UT Southwestern
Status: Recruiting
Contact: Ask Sarah hotline - 877-691-7274
Dallas, Texas, United States
Peninsula Oncology Centre
Status: Recruiting
Contact: Laurin Priddy - 214-648-1688
Frankston, Victoria, Australia
Sir Charles Gairdner Hospital
Status: Recruiting
Contact: Albert Goikhman - 61 (0)3 9771 8910
Perth, Western Australia, Australia
Chris O'Brien Lifehouse at RPA
Status: Recruiting
Contact: Judy Innes-Rowe - 08 63833280
Camperdown, Australia
Epworth Hospital
Status: Recruiting
Contact: Christine Merlino - +61 2 9515 7706
Melbourne, Australia
Northern Cancer Institute
Status: Recruiting
Contact: Felicity Osmond - +61 (3) 9936 8055
Sydney, Australia
Calvary Mater Newcastle
Status: Recruiting
Contact: Sally McCowatt - 02 9463 1181
Waratah, Australia
UCL - St. Luc
Status: Recruiting
Contact: Fiona Abell - +61 (0)2 4014 3571
Brussel, Belgium
Antwerp University Hospital
Status: Recruiting
Contact: Vanessa Erculisse - Vanessa.Erculisse@uclouvain.be
Edegem, Belgium
University Hopsital Ghent
Status: Recruiting
Contact: Ann Decoene - +32 3 8214719 - ann.decoene@uza.be
Ghent, Belgium
CHU Liege - Sart Tilman
Status: Recruiting
Contact: Veerle Surmont - veerle.surmont@uzgent.be
Liege, Belgium
Princess Margaret Hospital
Status: Recruiting
Contact: Bernard Duysinx - bduysinx@chu.ulg.ac.be
Toronto, Ontario, Canada
CHRU, Lille
Status: Recruiting
Contact: Andrea Foster - (416) 946-4501
Lille, France
Hôpitaux de Marseille
Status: Recruiting
Contact: Prof. Arnaud Scherpereel - 00 33 3 20 44 56 12
Marseille, France
Gustave Roussy
Status: Recruiting
Contact: Dr. Laurent Greillier - 00 33 4 91 96 59 01
Villejuif, France
Cliniche Humanitas Gavazzeni
Status: Recruiting
Contact: Dr. Planchard - 00 33 1 42 11 45 64
Bergamo, Italy
Kyushu Cancer Center
Status: Recruiting
Contact: Giovanni Ceresoli - 0039 035 420 4663
Fukuoka, Japan
Hiroshima University Hospital
Status: Recruiting
Contact: Dr. Takashi Seto - 81925413231
Hiroshima, Japan
Hyogo College of Medicine
Status: Recruiting
Contact: Yoshihiro Miyata - 81-82-257-5869
Hyogo, Japan
Okayama Rousai Hospital
Status: Recruiting
Contact: Dr. Taiichiro Otsuki - +81-798-45-6596
Okayama, Japan
Kinki University Hospital
Status: Recruiting
Contact: Dr. Nobukazu Fujimoto - 81-86-262-0131
Osaka, Japan
Juntendo University
Status: Recruiting
Contact: Dr. Toshio Shimizu - 81723-66-0221
Tokyo, Japan
Stichting Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis
Status: Recruiting
Contact: Takehito Shukuya - ＋81358021589
Amsterdam, Netherlands
Medisch Spectrum Twente, Enschede
Status: Recruiting
Contact: Marianne Mahn - +31(0)205127496 - m.mahn@nki.nl
Enschede, Netherlands
Atrium MC
Status: Recruiting
Contact: Ms. M. Mulder, MSc - +31 6 31 67 58 46 - M.Mulder@mst.nl
Heerlen, Netherlands
Atrium MC
Status: Recruiting
Contact: Carla Coenjaerd - 045-5766027 - c.coenjaerds@atriummc.nl
Heerlen, Netherlands
Erasmus MC
Status: Recruiting
Contact: Carla Coenjaerds - 045-5766027 - c.coenjaerds@atriummc.nl
Rotterdam, Netherlands
Auckland Oncology Research Centre
Status: Recruiting
Contact: Mrs. A. L. Geel - +31 (0)107030323 - a.geel@erasmusmc.nl
Auckland, New Zealand
Canterbury Regional Cancer & Haematology Service
Status: Recruiting
Contact: Vivian Sun - Vsun@adhb.govt.nz
Christchurch, New Zealand
Norwegian Radium Hospital
Status: Recruiting
Contact: Katie Moore - 6433641823
Oslo, Norway
The Medical Oncology Centre of Rosebank
Status: Recruiting
Contact: Dr. Odd Terje Brustugun - ot.brustugun@gmail.com
Johannesburg, South Africa
Mary Potter Oncology Center, Little Company of Mary Hospital
Status: Recruiting
Contact: Teresa Smit - +27 11 880 4169
Pretoria, South Africa
Institut Oncològic del Vallés Consorci Hospitalari Parc Tauli
Status: Recruiting
Contact: Marietjie Mouton - +27 12 346 6701
Barcelona, Spain
Vall d'Hebron University Hospital
Status: Recruiting
Contact: Jose Garcia Ruiz - +34 93 724 00 84
Barcelona, Spain
Ensayos Clínicos Oncología
Status: Recruiting
Contact: Marta Malo Perez - +34 93 274 60 00
Madrid, Spain
Hospital Madrid Norte- Sanchinarro, Centro Integral Oncológico Clara Campal (CIOCC)
Status: Recruiting
Contact: Dr. Santiago Ponce - +34 91 469 23 13
Madrid, Spain
Skane University Hospital
Status: Recruiting
Contact: Rocio Blanco - +34 91 756 79 84
Lund, Sweden
Karolinska University Hospital
Status: Recruiting
Contact: Dr. Ronny Ohman - : +46 (0)46 17 10 00
Stockholm, Sweden
University Hospital
Status: Recruiting
Contact: Gunnar Hillerdal - +46 (0)8 517 700 00
Uppsala, Sweden
Clatterbridge Cancer Centre
Status: Recruiting
Contact: Dr. Simon Ekman - +46 (0)18 611 00 00
Bebington, Wirral, United Kingdom
Southmead Hospital
Status: Recruiting
Contact: Laurie Lomax - 0151 482 7804 - Laurie.lomax@clatterbridgecc.nhs.uk
Bristol, United Kingdom
Addenbrooke's Hospital
Status: Recruiting
Contact: Deborah Warbrick - Deborah.Warbrick@nbt.nhs.uk
Cambridge, United Kingdom
Velindre Hospital Cardiff
Status: Recruiting
Contact: Marian Coliof - +44 (0)1223 216083 - cctc@addenbrookes.nhs.uk
Cardiff, United Kingdom
Broomfield Hospital
Status: Recruiting
Contact: Amanda Jackson - +44 (0)2920 615888 - Amanda.Jackson2@wales.nhs.uk
Chelmsford, United Kingdom
Tayside Cancer Centre
Status: Recruiting
Contact: Lyndsay Johnson - 01254 516 339 - lyndsay.johnson@meht.nhs.uk
Dundee, United Kingdom
Beatson Oncology Centre
Status: Recruiting
Contact: Valerie Walker - Tascfeasibility.tayside@nhs.net
Glasgow, United Kingdom
Royal Surrey County Hospital
Status: Recruiting
Contact: Julie Lang - julie.lang@ggc.scot.nhs.uk
Guildford, United Kingdom
Castle Hill Hospital
Status: Recruiting
Contact: Susanne Tluk, RN - 01483 571122 - s.tluk@nhs.net
Hull, United Kingdom
Kent Oncology Centre, Maidstone Hospital
Status: Recruiting
Contact: Karen Stubbs - karen.stubbs@hey.nhs.uk
Kent, United Kingdom
University of Leicester
Status: Recruiting
Contact: Karen McDonald - 01622 227093 - karenmcdonald@nhs.net
Leicester, United Kingdom
Guys Hospital
Status: Recruiting
Contact: Anita Kang - +44 (0)116 258 7598 - Anita.Kang@uhl-tr.nhs.uk
London, United Kingdom
St. Bartholomew's Hospital
Status: Recruiting
Contact: Dr. James Spicer, MD - +44 (0) 207188 4260
London, United Kingdom
Wythenshawe Hospital
Status: Recruiting
Contact: Dr. Jeremy Steele - +44 7957645383 - Jeremy.steele@bartshealth.nhs.uk
Manchester, United Kingdom
Freeman Hospital
Status: Recruiting
Contact: Dr. Paul Taylor - +44 (0)161 291 2829 - paul.taylor@uhsm.nhs.uk
Newcastle, United Kingdom
Derriford Hospital
Status: Recruiting
Contact: Chris Barron - 0191 213 8436 - chris.barron@nuth.nhs.uk
Plymouth, United Kingdom
Weston Park Hospital
Status: Recruiting
Contact: Dr. Amy Roy - 01752 432335
Sheffield, United Kingdom
Southampton General Hospital
Status: Recruiting
Contact: Carol Crabtree - c.crabtree@sheffield.ac.uk
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