Brief Title
A Phase 1 Dose Escalation Study of VS-5584 Administered in Combination With VS-6063, in Subjects With Relapsed Malignant Mesothelioma
Official Title
A Phase 1 Dose Escalation Study of VS-5584, a Dual PI3K/mTOR Inhibitor, Administered With a Fixed Dose of VS-6063, a Focal Adhesion Kinase Inhibitor, in Subjects With Relapsed Malignant Mesothelioma
Brief Summary
The purpose of this study is to evaluate rising dose levels of VS-5584 administered in
combination with a fixed dose of VS-6063 in subjects with relapsed malignant mesothelioma to
determine a recommended Phase 2 dose (RP2D) for further development of this combination in
this indication.
Detailed Description
This study is comprised of 2 sequential parts: Part 1 (Dose Escalation of VS-5584) and Part 2
(Expansion). Up to 56 evaluable subjects (i.e., subjects who complete at least 1 cycle [21
days] of therapy) will be enrolled, assuming that:
- Up to 6 dose levels of VS-5584 are studied in Part 1 (Dose Escalation of VS-5584) in
combination with a fixed dose of VS-6063 at 400 mg twice daily (BID) with a maximum of 6
subjects enrolled per VS-5584 dose level, for a total of up to 36 subjects (exclusive of
replacement subjects).
- Up to an additional 20 evaluable subjects may be enrolled in Part 2, the expansion
portion of the study. Subjects will be treated with VS-5584 at the RP2D and schedule
determined in the dose escalation portion of the study in combination with a fixed dose
of VS-6063.
Study Phase
Phase 1
Study Type
Interventional
Primary Outcome
Incidence of dose-limiting toxicities (DLTs)
Secondary Outcome
Pharmacokinetics of VS-5584 & VS-6063 maximum observed plasma concentration (Cmax)
Condition
Relapsed Malignant Mesothelioma
Intervention
VS-5584 and VS-6063
Study Arms / Comparison Groups
VS-5584 and VS-6063
Description:
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
21
Start Date
January 2015
Completion Date
October 2015
Primary Completion Date
October 2015
Eligibility Criteria
Inclusion Criteria:
1. Histopathologically-confirmed diagnosis of malignant mesothelioma (pleural or
peritoneal). Must have disease that has relapsed following at least one prior line of
chemotherapy.
2. Must have received at least 3 cycles of first-line chemotherapy.
3. Evaluable or measurable disease as assessed by Response Evaluation Criteria in Solid
Tumors (RECIST).
4. Must have archival tumor tissue available for biomarker analysis. A study-specific
tumor core biopsy, pleural effusion or ascites sample must be obtained prior to
treatment if archival tissue is not available.
5. Performance status according to the Karnofsky Performance Scale ≥70%.
6. Fasting blood glucose of ≤ 140 mg/dL (7.8 mmol/L).
7. Adequate renal function (creatinine ≤ 1.5x upper limit of normal [ULN]) and/or
glomerular filtration rate (GFR) of ≥50 mL/min.
8. Adequate hepatic function (total bilirubin ≤ 1.5x ULN; AST and ALT ≤ 3x ULN).
9. Adequate bone marrow function (hemoglobin ≥9.0 g/dL; platelets ≥100 x10^9 cells/L;
absolute neutrophil count ≥1.5x10^9 cells/L) without the use of hematopoietic growth
factors.
Exclusion Criteria:
1. Have had a previous extra pleural pneumonectomy (EPP).
2. Gastrointestinal condition which could interfere with the swallowing or absorption of
study drug.
3. Uncontrolled or severe concurrent medical condition (including uncontrolled brain
metastases).
4. Known history of stroke or cerebrovascular accident within 6 months prior to the first
dose of study drug.
5. Any evidence of serious active infection.
6. Undergoing active treatment for a secondary malignancy.
7. Cancer-directed therapy (chemotherapy, radiotherapy) within 21 days of the first dose
of study drug or 5 half-lives, whichever is shorter.
8. Major surgery within 28 days prior to the first dose of study drug.
9. Acute or chronic pancreatitis.
10. Diabetes mellitus requiring insulin treatment or subjects with a hemoglobin A1C
(HbA1C) >7%.
11. History or evidence of cardiac risk.
12. Known history of malignant hypertension.
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Hagop Youssoufian, ,
Location Countries
United Kingdom
Location Countries
United Kingdom
Administrative Informations
NCT ID
NCT02372227
Organization ID
VS-6063-104
Responsible Party
Sponsor
Study Sponsor
Verastem, Inc.
Study Sponsor
Hagop Youssoufian, Study Chair, Verastem, Inc.
Verification Date
January 2017