Clinical Trial - NCT02278250

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

Recruiting

Sponsor: EMD Serono Research & Development Institute, Inc.

Collaborators: Merck KGaA, Darmstadt, Germany

Information provided by (Responsible party): Sponsor

ClinicalTrials.gov Identifier: NCT02278250

Protocol Info

Short Description: Phase 1 VX-803 +/- Cytotoxic Chemotherapy in Solid Tumors
Long Description: 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
MGH Status: Open
Sponsor: Vertex
Disease Program: Phase I

Next Steps


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Purpose

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.
Condition Title Intervention Phase
Solid Tumor Advanced Solid Tumor M4344 Carboplatin Gemcitabine Cisplatin Phase 1
Study Type Interventional
Official Title 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

Primary Outcome Measures

Parts A, A2, 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] [Designated as safety issue: ]

Part A, A2: Maximum tolerated dose (MTD) and/or recommended Phase 2 (RP2D) of single-agent M4344 administered BIW or BID or once daily [Time Frame: Evaluation for dose-limiting toxicity will be during Cycle 1 (21 days) for each subject] [Designated as safety issue: ]

Part B: MTD and/or RP2D of M4344 administered in combination with carboplatin (Part B1), with gemcitabine (Part B2), and with cisplatin (B3) [Time Frame: Evaluation for dose-limiting toxicity will be during Cycle 1 (21 days) for each subject] [Designated as safety issue: ]


Secondary Outcome Measures

Part A, A2: Pharmacokinetics (PK) parameters of single-agent M4344 administered BIW or BID or once daily, derived from plasma concentration-time data [Time Frame: Day 1 through 15 of Cycle 1] [Designated as safety issue: ]

Parts A, A2, 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] [Designated as safety issue: ]

Part B: PK Parameters of M4344 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] [Designated as safety issue: ]

Part C: Progression Free Survival (PFS) and Response Duration (RD) as evaluated by RECIST 1:1 [Time Frame: Baseline until tumor progression] [Designated as safety issue: ]

Part C: PK parameter estimates of M4344 [Time Frame: Days -7 to -1 prior to Cycle 1 of Part C] [Designated as safety issue: ]

Estimated Enrollment: 151
Study Start Date: January 2015
Estimated Study Completion Date: September 2019
Estimated Primary Completion Date: September 2019
Arms Assigned Interventions

Experimental:Part A: M4344 BIW

Dose escalation of M4344 administered BIW as a single agent.
Drug:M4344

Experimental:Part A2: M4344 BID or once daily

Dose escalation of M4344 administered BID or once daily as a single agent.

Experimental:Part B1: M4344 + Carboplatin

Dose escalation of M4344 in combination with carboplatin.
Drug:Carboplatin

Experimental:Part B2: M4344 + Gemcitabine

Dose escalation of M4344 in combination with gemcitabine.
Drug:Gemcitabine

Experimental:Part B3: M4344 + Cisplatin

Dose escalation of M4344 in combination with cisplatin.
Drug:Cisplatin

Experimental:Part C: M4344 + Carboplatin or Cisplatin

An expanded cohort study to confirm the effect of M4344 in combination with carboplatin or cisplatin in participants with advanced serous ovarian cancer who have received prior therapy with carboplatin.

Eligibility

Ages Eligible for Study: N/A-N/A

Genders Eligible for Study: All

Accepts Healthly Volunteers: No

Inclusion Criteria:

  • Part A and A2: Participants with one histologically or cytologically confirmed malignant advanced solid tumor, for which no standard therapy is available which may convey clinical benefit
  • Part B: Participants with one histologically or cytologically confirmed malignant advanced solid tumor, for which no standard therapy is available which may convey clinical benefit and/or participants 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: Participants with advanced (locally advanced incurable or metastatic) histologically or cytologically confirmed high-grade serous ovarian cancer (high nuclear Grades 2 or 3). Participants 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, target-specific 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 participant

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 participants who are already pregnant or lactating, or plan to become pregnant within 6 months of the last dose of study drug are excluded. Female participants of childbearing potential must adhere to contraception guidelines. Female participants 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 participants 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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT02278250

Locations

  • United States, Massachusetts
    • Research site Boston, Massachusetts, United States, 02114
  • United States, Tennessee
    • Research site 1 Nashville, Tennessee, United States, 37203
    • Research site 2 Nashville, Tennessee, United States, 37232
  • Netherlands,
    • Research site Rotterdam, , Netherlands, 3075 EA
  • United Kingdom,
    • Research site London, , United Kingdom, W1G 6AD
    • Research site Sutton, , United Kingdom,

Sponsors and Collaborators

EMD Serono Research & Development Institute, Inc.

Merck KGaA, Darmstadt, Germany

More Information

No publications provided

Responsible Party: Sponsor
ClinicalTrials.gov Identifier: NCT02278250
Other Study ID Numbers: VX14-803-001
Study First Received:
Last Updated:
Health Authority:

Keywords provided by EMD Serono:

VX14-803-001

VX-803

M4344

Advanced Solid Tumor

Cytotoxic Chemotherapy

Gemcitabine

Cisplatin

Carboplatin

Additional relevant MeSH terms:

Neoplasms

Cisplatin

Gemcitabine

Carboplatin

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.







ClinicalTrials.gov processed this data on May 30, 2019