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Phase I Dose Escalation Study of VS-6063 in Japanese Subjects With Non-Hematologic Malignancies

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ClinicalTrials.gov Identifier: NCT01943292
Recruitment Status : Completed
First Posted : September 16, 2013
Results First Posted : November 20, 2015
Last Update Posted : March 9, 2017
Sponsor:
Information provided by (Responsible Party):
Verastem, Inc.

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Non Hematologic Cancers
Intervention Drug: Defactinib
Enrollment 9
Recruitment Details First subject enrolled 02Sep2013; Last subject enrolled 07Jan2014; all patients enrolled at one site in Japan.
Pre-assignment Details There were no significant events and approaches for overall study. There was one screen failure.
Arm/Group Title Defactinib 200 mg Bid Defactinib 400 mg Bid Defactinib 600 mg Bid
Hide Arm/Group Description 200 mg bid (twice a day) po (by mouth) defactinib 400 mg bid po defactinib 600 mg bid po defactinib
Period Title: Overall Study
Started 3 3 3
Completed Cycle 1 3 3 3
Completed Treatment 3 3 3
Completed Follow-Up 2 3 3
Completed 2 3 3
Not Completed 1 0 0
Reason Not Completed
Withdrawal by Subject             1             0             0
Arm/Group Title Defactinib 200 mg Bid Defactinib 400 mg Bid Defactinib 600 mg Bid Total
Hide Arm/Group Description 200 mg po bid defactinib 400 mg po bid defactinib 600 mg po bid defactinib Total of all reporting groups
Overall Number of Baseline Participants 3 3 3 9
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 3 participants 3 participants 3 participants 9 participants
60.7  (6.51) 67.0  (7.21) 53.7  (16.56) 60.4  (11.20)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 3 participants 3 participants 9 participants
Female
0
   0.0%
0
   0.0%
2
  66.7%
2
  22.2%
Male
3
 100.0%
3
 100.0%
1
  33.3%
7
  77.8%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 3 participants 3 participants 9 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
3
 100.0%
3
 100.0%
3
 100.0%
9
 100.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
White
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Assess the Safety and Tolerability of Defactinib (VS-6063) in Japanese Subjects With Non-hematologic Malignancies
Hide Description

A composite by dose level to include incidence of AEs, SAEs, dose interruptions and dose reductions as a measure of safety and tolerability. Abnormal Clinical significant laboratory results, ECG measurements, vital signs measurement, physical examination findings, and ECOG performance status were captured as adverse events.

The severity of AEs were evaluated according to CTCAE (Common Toxicity Criteria for Adverse Effects) 4.03

Time Frame From start of treatment to end of treatment, an expected average of 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Defactinib 200 mg Bid Defactinib 400 mg Bid Defactinib 600 mg Bid
Hide Arm/Group Description:
200 mg po bid defactinib
400 mg po bid defactinib
600 mg po bid defactinib
Overall Number of Participants Analyzed 3 3 3
Measure Type: Number
Unit of Measure: participants
At least 1 TEAE (treatment emergent AE) 3 3 3
At least 1 TEAE related to study drug 3 3 3
Non-Lab TEAE with Severity ≥ Grade 3 0 0 0
Lab TEAE with Severity ≥ Grade 3 1 0 0
At least 1 Serious TEAE 0 0 0
Dose Interruptions 1 1 0
Dose Reductions 0 0 0
2.Secondary Outcome
Title Define the Maximum Tolerated Dose (MTD), if Achieved, and Establish the Recommended Phase 2 Dose (RP2D) of Defactinib (VS-6063) in Japanese Subjects.
Hide Description The RP2D will be determined based on the MTD of defactinib (VS-6063) as determined by number of participants with dose limiting toxicities (DLTs) related to defactinib.
Time Frame From start of treatment to end of cycle 1 (21 day cycles)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Defactinib 200 mg Bid Defactinib 400 mg Bid Defactinib 600 mg Bid
Hide Arm/Group Description:
200 mg po bid defactinib
400 mg po bid defactinib
600 mg po bid defactinib
Overall Number of Participants Analyzed 3 3 3
Measure Type: Number
Unit of Measure: mg
NA [1]  NA [1]  NA [1] 
[1]
There were no DLTs. MTD was not reached. RP2D is 400 mg bid.
3.Secondary Outcome
Title Assess the Pharmacokinetics, Metabolism and Elimination of Defactinib (VS-6063) in Plasma and Urine.
Hide Description PK parameters, including but not limited to plasma concentration, AUC (Area Under Curve) 0-t, Cmax, Tmax, and T1/2. Total 24-hour urine output will be collected in conjunction with PK sampling to assess the elimination of defactinib (VS-6063) and its potential metabolites.
Time Frame Time points at Day 1 and Day 15 in Cycle 1
Outcome Measure Data Not Reported
4.Secondary Outcome
Title Evaluate the Efficacy (Response Rate and Progression-free Survival) of Subjects Treated With Defactinib (VS-6063).
Hide Description Response rate and progression-free survival, as determined by Response Evaluation Criteria In Solid Tumors (RECIST), version 1.1
Time Frame Every 8 weeks up to end of treatment, an expected average of 12 weeks
Outcome Measure Data Not Reported
Time Frame Treatment Emergent Adverse Events (TEAEs) include all events (related and unrelated) from the time patient doses through 30 days post last dose of study treatment
Adverse Event Reporting Description The systematic method was through regular investigator assessment and regular laboratory testing.
 
Arm/Group Title Defactinib 200 mg Bid Defactinib 400 mg Bid Defactinib 600 mg Bid
Hide Arm/Group Description 200 mg po bid defactinib 400 mg po bid defactinib 600 mg po bid defactinib
All-Cause Mortality
Defactinib 200 mg Bid Defactinib 400 mg Bid Defactinib 600 mg Bid
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Defactinib 200 mg Bid Defactinib 400 mg Bid Defactinib 600 mg Bid
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/3 (0.00%)   0/3 (0.00%)   0/3 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Defactinib 200 mg Bid Defactinib 400 mg Bid Defactinib 600 mg Bid
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   3/3 (100.00%)   3/3 (100.00%)   3/3 (100.00%) 
Blood and lymphatic system disorders       
Anemia  1  0/3 (0.00%)  0/3 (0.00%)  2/3 (66.67%) 
Thrombocytopenia  1  1/3 (33.33%)  0/3 (0.00%)  0/3 (0.00%) 
Gastrointestinal disorders       
Diarrhea  1  0/3 (0.00%)  1/3 (33.33%)  2/3 (66.67%) 
Nausea  1  1/3 (33.33%)  0/3 (0.00%)  1/3 (33.33%) 
Abdominal Distension  1  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%) 
Abdominal Pain  1  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%) 
Stomatitis  1  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%) 
General disorders       
Fatigue  1  2/3 (66.67%)  1/3 (33.33%)  3/3 (100.00%) 
Oedema Peripheral  1  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%) 
Infections and infestations       
Nasopharyngitis  1  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%) 
Injury, poisoning and procedural complications       
Lower Limb Fracture  1  1/3 (33.33%)  0/3 (0.00%)  0/3 (0.00%) 
Investigations       
Blood Bilirubin Increased  1  3/3 (100.00%)  2/3 (66.67%)  2/3 (66.67%) 
Aspartate Aminotransferase Increased  1  1/3 (33.33%)  0/3 (0.00%)  1/3 (33.33%) 
Blood Alkaline Phosphatase Increased  1  2/3 (66.67%)  0/3 (0.00%)  0/3 (0.00%) 
Alanine Aminotransferase Increased  1  1/3 (33.33%)  0/3 (0.00%)  0/3 (0.00%) 
Blood Creatinine Increased  1  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%) 
Blood Phosphorus Increased  1  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%) 
Blood Pressure Increased  1  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%) 
Metabolism and nutrition disorders       
Decreased Appetite  1  2/3 (66.67%)  1/3 (33.33%)  1/3 (33.33%) 
Hyperkalaemia  1  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%) 
Hyperuricaemia  1  1/3 (33.33%)  0/3 (0.00%)  0/3 (0.00%) 
Hypouricaemia  1  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%) 
Musculoskeletal and connective tissue disorders       
Pain in Extremity  1  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Cancer Pain  1  1/3 (33.33%)  1/3 (33.33%)  0/3 (0.00%) 
Nervous system disorders       
Headache  1  0/3 (0.00%)  1/3 (33.33%)  1/3 (33.33%) 
Dizziness  1  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%) 
Peripheral Sensory Neuropathy  1  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%) 
Renal and urinary disorders       
Proteinuria  1  1/3 (33.33%)  0/3 (0.00%)  0/3 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Cough  1  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%) 
Dyspnoea  1  1/3 (33.33%)  0/3 (0.00%)  0/3 (0.00%) 
Skin and subcutaneous tissue disorders       
Alopecia  1  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%) 
Dermatitis  1  0/3 (0.00%)  0/3 (0.00%)  1/3 (33.33%) 
Pain of Skin  1  0/3 (0.00%)  1/3 (33.33%)  0/3 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDra 16.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The site is not able to publish any clinical trial results without first seeking permission from Verastem.
Results Point of Contact
Name/Title: Lou Vaickus, MD, FACP/Chief Medical Officer
Organization: Verastem
Phone: 781-292-4200
Responsible Party: Verastem, Inc.
ClinicalTrials.gov Identifier: NCT01943292     History of Changes
Other Study ID Numbers: VS-6063-102
First Submitted: September 11, 2013
First Posted: September 16, 2013
Results First Submitted: June 9, 2015
Results First Posted: November 20, 2015
Last Update Posted: March 9, 2017