Clinical Trials Logo

Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT01870609
Other study ID # VS-6063-202
Secondary ID
Status Terminated
Phase Phase 2
First received May 29, 2013
Last updated January 26, 2017
Start date September 2013
Est. completion date January 2016

Study information

Verified date March 2016
Source Verastem, Inc.
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical 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 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.


Recruitment information / eligibility

Status Terminated
Enrollment 344
Est. completion date January 2016
Est. primary completion date January 2016
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
defactinib (VS-6063)

Placebo
Sugar pill manufactured to mimic defactinib tablet

Locations

Country Name City State
Australia Chris O'Brien Lifehouse at RPA Camperdown
Australia Monash Cancer Center East Bentlrigh
Australia Peninsula Oncology Centre Frankston Victoria
Australia Epworth Hospital Melbourne
Australia Sir Charles Gairdner Hospital Perth Western Australia
Australia Northern Cancer Institute Sydney
Australia Calvary Mater Newcastle Waratah
Australia Princess Alexandra Hospital +61(0)7 3176 5054 Woolloongabba
Belgium 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
Canada Princess Margaret Hospital Toronto Ontario
France CHRU, Lille Lille
France Hôpitaux de Marseille Marseille
France Gustave Roussy Villejuif
Italy Cliniche Humanitas Gavazzeni Bergamo
Italy Istituto Oncologico Veneto Padova
Japan 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
Netherlands Stichting Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Amsterdam
Netherlands Medisch Spectrum Twente, Enschede Enschede
Netherlands Atrium MC Heerlen
Netherlands Erasmus MC Rotterdam
New Zealand Auckland Oncology Research Centre Auckland
New Zealand Canterbury Regional Cancer & Haematology Service Christchurch
Norway Norwegian Radium Hospital Oslo
Poland Centrum Pulmonologii Ii Torakochirurgii w Bystrej Bystra
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
Spain 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
Sweden Skane University Hospital Lund
Sweden Karolinska University Hospital Stockholm
Sweden University Hospital Uppsala
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 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 Southampton General Hospital Southampton
United States Johns Hopkins Sidney Kimmel Comprehensive Cancer Center Baltimore Maryland
United States Jacobi Medical Center Bronx New York
United States Roswell Park Cancer Institute Buffalo New York
United States University of Chicago Medical Center Chicago Illinois
United States Cleveland Clinic Cleveland Ohio
United States UT Southwestern Dallas Texas
United States Sarah Cannon Research Institute Nashville Tennessee
United States Memorial Sloan Kettering Cancer Center New York New York
United States Abramson Cancer Center Philadelphia Pennsylvania
United States Mayo Clinic Rochester Minnesota
United States University of California San Francisco Medical Center San Francisco California
United States Cleveland Clinic Florida Weston Florida

Sponsors (1)

Lead Sponsor Collaborator
Verastem, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  France,  Italy,  Japan,  Netherlands,  New Zealand,  Norway,  Poland,  South Africa,  Spain,  Sweden,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Other Determine the time to new lesion in subjects receiving defactinib (VS-6063) or placebo 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. Every 6-8 weeks from baseline until end of treatment, an expected average of 4 months
Other Evaluate the relationship of defactinib (VS-6063) pharmacokinetics (PK) and outcome PK parameters, including but not limited to plasma concentration, AUC (Area Under Curve) 0-t, Cmax, Tmax, and T1/2, compared with outcome Time points at Week 4, Week 7, Week 10 and Week 13
Other Evaluate the population pharmacokinetics of defactinib (VS-6063) in subjects with malignant pleural mesothelioma PK parameters, including but not limited to plasma concentration, AUC (Area Under Curve) 0-t, Cmax, Tmax, and T1/2 Time points at Week 4, Week 7, Week 10 and Week 13
Other Evaluate the safety and tolerability of defactinib (VS-6063) in subjects with malignant pleural mesothelioma 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 From start of treatment to end of treatment, an expected average of 4 months
Other To collect EuroQol 5-Dimensional Health Questionnaire (EQ-5D) for health economics purposes Every 3-4 weeks from baseline through end of treatment, an expected average of 4 months
Primary 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 From randomization to end of life, an expected average of 12 months
Primary 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 From date of randomization to earliest documented date of progression, an expected average of 4 months
Secondary 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. Every 3-4 weeks from baseline through end of treatment, an expected average of 4 months
Secondary 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. Every 6-8 weeks from baseline through end of treatment, an expected average of 4 months
See also
  Status Clinical Trial Phase
Recruiting NCT06037941 - Using E-Nose Technology to Measure Response to Treatment in People With Malignant Pleural Mesothelioma N/A
Completed NCT01675765 - Safety and Efficacy of Listeria in Combination With Chemotherapy as Front-line Treatment for Malignant Pleural Mesothelioma Phase 1
Withdrawn NCT04201145 - Pembrolizumab + Defactinib In Pleural Mesothelioma Phase 1
Completed NCT03048474 - Ipilimumab and Nivolumab in the Treatment of Malignant Pleural Mesothelioma Phase 2
Completed NCT02369198 - MesomiR 1: A Phase I Study of TargomiRs as 2nd or 3rd Line Treatment for Patients With Recurrent MPM and NSCLC Phase 1
Active, not recruiting NCT00886028 - Palliative Treatment With Liposomal Doxorubicin Plus Cisplatin for Patients With Malignant Pleural Mesothelioma Phase 2
Completed NCT00272558 - Study of Carboplatin and Vinorelbine in Malignant Pleural Mesothelioma Phase 2
Active, not recruiting NCT02436733 - Pleurectomy/ Decortication (P/D) Preceded or Followed by Chemotherapy in Patients With Early Stage MPM Phase 2
Completed NCT04843007 - Alvopem® (Pemetrexed) Safety Assessment
Completed NCT01721018 - Intrapleural Administration of HSV1716 to Treat Patients With Malignant Pleural Mesothelioma. Phase 1/Phase 2
Active, not recruiting NCT00797719 - Short Neoadjuvant Hemithoracic IMRT for MPM Phase 1/Phase 2
Completed NCT00386815 - Safety Confirmation Study of Pemetrexed Plus Cisplatin in Patients With Malignant Pleural Mesothelioma Phase 2
Recruiting NCT03715933 - Phase 1 Study of INBRX-109 in Subjects With Locally Advanced or Metastatic Solid Tumors Including Sarcomas Phase 1
Completed NCT04775446 - Evaluation of the Clinical/Biological Characteristics, Efficacy and Safety of Patients With Malignant Pleural Mesothelioma, Treated by Immunotherapy
Completed NCT01865045 - Pharmacogenetics Of Vinorelbine In Malignant Pleural Mesothelioma Patients
Completed NCT01644994 - Intracavitary Cisplatin-Fibrin Localized Chemotherapy After P/D or EPP for Malignant Pleural Mesothelioma Phase 1/Phase 2
Completed NCT00571298 - Extrapleural Pneumonectomy /Pleurectomy Decortication, IHOC Cisplatin and Gemcitabine With Amifostine and Sodium Thiosulfate Cytoprotection for Resectable Malignant Pleural Mesothelioma Phase 1
Recruiting NCT01343264 - Trimodality Therapy for Malignant Pleural Mesothelioma N/A
Active, not recruiting NCT04162015 - A Study of Nivolumab and Chemotherapy Followed by Surgery for Mesothelioma Phase 1
Recruiting NCT04400539 - The IMmunotherapy Pleural 5-ALA PDT Phase 2