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

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, and cisplatin to determine the safety and maximum tolerated dose.
Not Available
Phase I
Adults
Not Available
Not Available
Not Available
National
Vanderbilt University
09-03-2015
Treatment
VICCPHI14126
NCT02278250

Eligibility

18 Years
BOTH
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 B1: 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 would be considered standard of care.

Parts C1, C2, and C3: Participants with 1 histologically or cytologically confirmed malignant advanced solid tumors for which no recommended standard therapy is available (that is, participants who have exhausted all standard of care options according to National Comprehensive Cancer Network [NCCN] Guidance) which may convey clinical benefit, and whose tumor has at least 1 of the following biomarkers as determined by a central trial assay or by an assay with appropriate regulatory status: - C1: loss-of-function mutations in the gene ARID1A - C2: loss-of-function mutations in the genes ATRX and/or DAXX - C3: loss-of-function mutation in the gene ataxia telangiectasia mutated (ATM) - This mandatory biomarker assessment must be conducted during prescreening on a fresh tumor biopsy (or a biopsy obtained after the end of the previous treatment regimen). If this is not possible for medical reason(s), available archival tumor material can be used (historical data should not be used to confirm biomarker status)

Measurable disease according to RECIST criteria (Version 1.1)

WHO performance status of 0 or 1

Life expectancy of greater than or equal to (>=)12 weeks

Hematological and biochemical indices within acceptable ranges at Screening

Other protocol defined inclusion criteria could apply



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 B1: More than 6 cycles of prior therapy with carboplatin

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. Part B1: Any known history of Grade 4 thrombocytopenia with any prior chemotherapy regimen (not applicable for Parts C1, C2, and C3)

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 less than or equal to (
Serious co-morbid medical conditions, including clinically-significant cardiac disease

Other protocol defined exclusion criteria could apply

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