Clinical Trials /

An Open-Label Study of the Safety, Tolerability, and Pharmacokinetic/Pharmacodynamic Profile of VX-803/M4344 as a Single Agent and in Combination With Cytotoxic Chemotherapy in Participants With Advanced Solid Tumors

NCT02278250

Description:

The purpose of this study is to evaluate the safety and tolerability of multiple ascending doses of single-agent M4344 administered twice-weekly (BIW), twice daily (BID) or once daily dose schedule in participants with advanced solid tumors. This investigation is a three part study examining M4344 alone and in combination with carboplatin, gemcitabine, and cisplatin to determine the safety and maximum tolerated dose.

Related Conditions:
  • Malignant Solid Tumor
  • Ovarian Serous Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: An Open-Label Study of the Safety, Tolerability, and Pharmacokinetic/Pharmacodynamic Profile of VX-803 as a Single Agent and in Combination With Cytotoxic Chemotherapy in Subjects With Advanced Solid Tumors
  • Official Title: An Open-Label Study of the Safety, Tolerability, and Pharmacokinetic/Pharmacodynamic Profile of VX-803 as a Single Agent and in Combination With Cytotoxic Chemotherapy in Subjects With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: VX14-803-001
  • NCT ID: NCT02278250

Conditions

  • Solid Tumor
  • Advanced Solid Tumor

Interventions

DrugSynonymsArms
VX-803Part A: VX-803
CarboplatinPart B1: VX-803 + Carboplatin
GemcitabinePart B2: VX-803 + Gemcitabine
CisplatinPart B3: VX-803 + Cisplatin

Purpose

The purpose of this study is to evaluate the safety and tolerability of multiple ascending doses of single-agent VX-803 administered twice-weekly (BIW) in subjects with advanced solid tumors. This investigation is a three part study examining VX-803 alone and in combination with carboplatin, gemcitabine, and cisplatin to determine the safety and maximum tolerated dose.

Trial Arms

NameTypeDescriptionInterventions
Part A: VX-803ExperimentalDose escalation of VX-803 administered as a single agent
  • VX-803
Part B1: VX-803 + CarboplatinExperimentalDose escalation of VX-803 in combination with carboplatin.
  • VX-803
  • Carboplatin
Part B2: VX-803 + GemcitabineExperimentalDose escalation of VX-803 in Combination with gemcitabine.
  • VX-803
  • Gemcitabine
Part B3: VX-803 + CisplatinExperimentalDose escalation of VX-803 in combination with cisplatin
  • VX-803
  • Cisplatin
Part C: VX-803 + Carboplatin or CisplatinExperimentalAn expanded cohort study to confirm the effect of VX-803 in combination with carboplatin or cisplatin in subjects with advanced serous ovarian cancer who have received prior therapy with carboplatin.
  • VX-803
  • Carboplatin
  • Cisplatin

Eligibility Criteria

        Inclusion Criteria:

          -  Part A: Subjects with one histologically or cytologically confirmed malignant advanced
             solid tumor, for which no standard therapy is available which may convey clinical
             benefit

          -  Part B: Subjects with one histologically or cytologically confirmed malignant advanced
             solid tumor, for which no standard therapy is available which may convey clinical
             benefit and/or subjects must have progressed after at least 1 prior chemotherapy
             regimen in the metastatic setting, and for which carboplatin (for Part B1),
             gemcitabine (for Part B2), or cisplatin (for Part B3) would be considered standard of
             care.

          -  Part C: Subjects with advanced (locally advanced incurable or metastatic)
             histologically or cytologically confirmed high-grade serous ovarian cancer (high
             nuclear Grades 2 or 3). Subjects should have either platinum-refractory (disease
             progression during initial platinum therapy) or platinum-resistant (disease
             progression <6 months after completion of platinum therapy) disease.

          -  Measurable disease according to RECIST criteria (Version 1.1)

          -  WHO performance status of 0 or 1

          -  Life expectancy of ≥12 weeks

          -  Hematological and biochemical indices within acceptable ranges at Screening.

        Exclusion Criteria:

          -  Radiotherapy, unless brief course for palliative therapy, endocrine therapy,
             immunotherapy, or chemotherapy during the 4 weeks (6 weeks for nitrosoureas and
             Mitomycin-C, and 4 weeks for investigational medicinal products) or 4 drug half-lives
             before first dose of study drug, whichever is greater

          -  Part B: More than 6 cycles of prior therapy with carboplatin

          -  Parts B1, B3, and C: During prior platinum therapy, requirement for dose reduction or
             discontinuation of carboplatin or cisplatin for toxicity or lack of tolerability

          -  Ongoing toxic manifestations of previous treatments. Exceptions to this are alopecia
             or certain Grade 1 toxicities, which in the opinion of the investigator should not
             exclude the subject

             a. Any known history of Grade 4 thrombocytopenia with any prior chemotherapy regimen

          -  Spinal cord compression or brain metastases unless asymptomatic, treated, stable, and
             not requiring steroids for at least 4 weeks before first dose of study drug

          -  Female subjects who are already pregnant or lactating, or plan to become pregnant
             within 6 months of the last dose of study drug are excluded. Female subjects of
             childbearing potential must adhere to contraception guidelines. Female subjects will
             be considered to be of nonchildbearing potential if they have undergone surgical
             hysterectomy or bilateral oophorectomy or have been amenorrheic for over 2 years with
             a screening serum follicle-stimulating hormone (FSH) level within the laboratory's
             reference range for postmenopausal females.

          -  Male subjects with partners of childbearing potential must agree to adhere to
             contraception guidelines. Men with pregnant or lactating partners or partners who plan
             to become pregnant during the study or within 6 months of the last dose of study drug
             are excluded.

          -  Major surgery ≤4 weeks before first dose of study drug or incomplete recovery from a
             prior major surgical procedure

          -  Serious co-morbid medical conditions, including clinically-significant cardiac disease
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Parts A, B, C: Safety parameters, including adverse events, clinical laboratory values (serum chemistry and hematology), vital signs, and electrocardiogram (ECG) assessments
Time Frame:From Baseline until 14 Days after discontinuation of study treatment
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Part A: Pharmacokinetics (PK) parameters of single-agent VX-803 administered BIW, derived from plasma concentration-time data
Time Frame:Day 1 through 15 of Cycle 1
Safety Issue:
Description:
Measure:Parts A, B, C: Objective tumor response (OR) and disease stabilization (SD) as evaluated by Response Criteria Evaluation (Response Evaluation Criteria in Solid Tumors [RECIST]) 1:1
Time Frame:Every 2 Cycles (6 weeks) until tumor progression
Safety Issue:
Description:
Measure:Part B: PK Parameters of VX-803 administered in combination with carboplatin (Part B1), with gemcitabine (Part B2), and with cisplatin (Part B3), derived from plasma concentration-time data
Time Frame:Day 1 through 9 of Cycle 1
Safety Issue:
Description:
Measure:Part C: Progression Free Survival (PFS) and Response Duration (RD) as evaluated by RECIST 1:1
Time Frame:Baseline until tumor progression
Safety Issue:
Description:
Measure:Part C: PK parameter estimates of VX-803
Time Frame:Days -7 to -1 prior to Cycle 1 of Part C
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Vertex Pharmaceuticals Incorporated

Last Updated

June 1, 2017