Spots Global Cancer Trial Database for Mocetinostat With Vinorelbine in Children, Adolescents & Young Adults With Refractory and/or Recurrent Rhabdomyosarcoma

Study Description

Brief Summary: This phase I trial studies the side effects and best dose of mocetinostat when given together with vinorelbine to see how well it works in treating children, adolescents, and young adults with rhabdomyosarcoma that has spread to nearby tissues or lymph nodes and cannot be removed by surgery (locally advanced unresectable) or has spread to other places in the body (metastatic), and does not respond to treatment (refractory) or has come back (relapsed). Mocetinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as vinorelbine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving mocetinostat and vinorelbine may work better in treating children, adolescents, and young adults with rhabdomyosarcoma compared to vinorelbine alone.

Detailed Description: PRIMARY OBJECTIVES: I. To determine the first cycle dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), and a biologically effective and recommended phase 2 dose (RP2D) of mocetinostat administered orally three times per week for a total of 9 doses per 21 day cycle given in combination with vinorelbine on days 1, 8, 15 of 21 day cycles in subjects with refractory or recurrent rhabdomyosarcoma (RMS). (Phase 1 Dose Escalation) II. To determine the progression-free survival (PFS), defined as time from first dose of vinorelbine to tumor progression or death due to any cause, at the RP2D of mocetinostat administered orally three times per week starting on day 3 for a total of 9 doses per 21 day cycle given in combination with vinorelbine on days 1, 8, 15 of a 21 day cycle in subjects with refractory or recurrent RMS. (Expansion Cohort) SECONDARY OBJECTIVES: I. Safety profile of mocetinostat in combination with vinorelbine as characterized by adverse event (AE) type, severity, timing and relationship to study drugs, as well as laboratory abnormalities in the first and subsequent treatment cycles. (Phase 1 Dose Escalation) II. Pharmacokinetics (PK) of mocetinostat in plasma. (Phase 1 Dose Escalation) III. Clinical benefit rate (CBR = complete response \[CR\] + partial response \[PR\] and stable disease \[SD\]) of mocetinostat + vinorelbine in metastatic/refractory/unresectable RMS. (Phase 1 Dose Escalation) IV. Antitumor activity of mocetinostat + vinorelbine in refractory/recurrent RMS as measured by overall response rate (ORR), duration of response (DOR), disease control (DC), duration of disease control, as well as progression-free survival (PFS). (Phase 1 Dose Escalation) V. Pharmacodynamics of mocetinostat on molecular targets in surrogate tissue. (Phase 1 Dose Escalation and Expansion Cohort) VI. Exploratory biomarker development to enable prediction of drug toxicity, tumor response and the mechanism(s) of acquired study drug resistance. (Phase 1 Dose Escalation and Expansion Cohort) VII. Obtain RMS tissue biological samples pre-treatment and at progression to assess for differences in gene expression by next gen (generation) sequencing and ribonucleic acid (RNA) sequencing (seq). (Phase 1 Dose Escalation and Expansion Cohort) VIII. Antitumor activity of mocetinostat + vinorelbine in metastatic/refractory RMS as measured by overall response rate (ORR) and duration of response (DOR), disease control (DC), duration of disease control, as well as progression-free survival (PFS) according to Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1. (Expansion Cohort) IX. Safety and tolerability of mocetinostat and vinorelbine as characterized by adverse event type, severity, timing and relationship to study drug, as well as laboratory abnormalities. (Expansion Cohort) OUTLINE: This is a phase I, dose-escalation study of mocetinostat followed by additional studies.

Keywords

Eligibility

Minimum Age: 13 Years

Eligible Ages: CHILD, ADULT, OLDER_ADULT

Sex: ALL

Healthy Volunteers: No

Locations

Contact Details

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