Mocetinostat With Vinorelbine in Children, Adolescents & Young Adults With Refractory and/or Recurrent Rhabdomyosarcoma

NCT04299113 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 19-000353NCI-2019-08263
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

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.

Conditions

Rhabdomyosarcoma

Keywords

Locally Advanced Rhabdomyosarcoma; Recurrent Rhabdomyosarcoma; Refractory Rhabdomyosarcoma; Unresectable Rhabdomyosarcoma

Outcome Measures

Primary Outcomes (2)

• To describe any dose-limiting toxicity (DLT)

  Percentage of subjects with dose-limiting toxicities (DLTs) as assessed by NCI CTCAE (Version 4.03)

  1 year

• To determine the maximum tolerated dose (MTD) or highest protocol defined doses (in the absence of exceeding the MTD)

  The MTD is the highest dose associated with first-cycle DLT in \< 33% of subjects

  1 year

Secondary Outcomes (10)

• To determine the Recommended Phase 2 Dose (RP2D) for mocetinostat in combination with vinorelbine

  1 year

• Incidence of Adverse Events (AEs) as assessed by NCI CTCAE (Version 4.03)

  1 year

• Objective Tumor Response

  2 years

• Progression Free Survival (PFS)

  2 years

• Disease Control (DC)

  2 years

Study Arms (1)

Treatment (vinorelbine, mocetinostat)

EXPERIMENTAL

Participants receive mocetinostat in combination with vinorelbine

Drug: Vinorelbine; Drug: Mocetinostat

Interventions

Vinorelbine DRUG

Given IV

Also known as: 3'',4''-Didehydro-4''-deoxy-C''-norvincaleukoblastine, 5''-Nor-Anhydrovinblastine, 71486-22-1, Dihydroxydeoxynorvinkaleukoblastine, nor-5''-Anhydrovinblastine, vinorelbine, VINORELBINE

Treatment (vinorelbine, mocetinostat)

Mocetinostat DRUG

Given PO

Also known as: 726169-73-9, Benzamide, N-(2-aminophenyl)-4-[[[4-(3-pyridinyl)-2-pyrimidinyl]amino]methyl]-, MG-0103, MGCD0103, MGCD0103, N-(2-aminophenyl)-4-((4-pyridin-3-ylpyrimidin-2-ylamino)methyl)benzamide

Treatment (vinorelbine, mocetinostat)

Eligibility Criteria

• Age: 13 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing and able to provide written Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved informed consent. For subjects \< 18 years of age, their parents or legal guardians must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines
• Have histologically or cytological confirmed diagnosis of rhabdomyosarcoma with locally advanced/unresectable, metastatic, refractory or relapsed disease who have failed standard therapy and for whom no known curative therapy exists
• Measurable disease according to RECIST version 1.1
• Prior cancer therapy: Subjects may have received any number of prior therapy regimens. In the investigator's opinion, subjects must have tolerated prior cytotoxic therapies well and have adequate bone marrow reserve. At the time of treatment initiation, at least 3 weeks must have elapsed after prior cytotoxic chemotherapy. At least 7 days must have elapsed since completion of any prior non-cytotoxic cancer therapy and any associated AEs must have resolved
• Prior radiotherapy is allowed if \>= 2 weeks have elapsed for local palliative radiation therapy (XRT) (small port); \>= 6 months must have elapsed if prior total body irradiation, craniospinal XRT or if \> 50% radiation of the pelvis; \> 6 weeks must have elapsed if other substantial bone marrow radiation (defined per principal investigator's \[PI's\] discretion). Subjects who have received brain irradiation must have completed whole brain radiotherapy and/or gamma knife at least 4 weeks prior to enrollment
• Subjects with controlled asymptomatic central nervous system (CNS) involvement are allowed in absence of therapy with anticonvulsants. Subjects not requiring steroids or requiring steroids at a stable dose (=\< 4 mg/day dexamethasone or equivalent) for at least 2 weeks are eligible
• Resolution of all acute toxic effects (excluding alopecia) of any prior anti-cancer therapy to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (version 4.03) grade \< 1 or to the baseline laboratory values as defined below
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) =\< 2 in subjects \>= 17 years old; or Karnofsky/Lansky \> 50 in subjects \< 16 years old
• Subjects age \> 18 years for first cohort. Subjects must be \> 12 years old for the second and subsequent cohorts
• Life expectancy of at least 3 months
• Absolute neutrophil count (ANC) \>= 1000/mm\^3 (\>= 1.0 x 10\^9/L)
• Platelets (PLT) \>= 100,000/mm\^3 (\>= 100 x 10\^9/L) (transfusion independent, defined as not receiving platelet transfusions within a 7 day period prior to screening)
• Hemoglobin \> 9.0 g/dL (transfusions are allowed)
• Serum creatinine =\< 1.5 x upper limit of normal (ULN) or creatinine clearance \> 60 mL/min
• Total serum bilirubin =\< 1.5 x ULN; =\< 5 x ULN if Gilbert's syndrome

You may not qualify if:

• Current participation in another therapeutic clinical trial
• Symptomatic brain metastases
• History of previous cancer (non RMS), except squamous cell or basal-cell carcinoma of the skin or any in situ carcinoma that has been completely resected, which required therapy within the previous 3 years. Other low grade cancers can be reviewed and allowed at the discretion of the PI
• Incomplete recovery from any surgery (other than central venous catheter or port placement) prior to treatment
• Any of the following in the past 6 months: pericarditis, pericardial effusion, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis, symptomatic bradycardia, requirement for anti-arrhythmic medication
• History of prolonged corrected QT (QTc) interval (e.g., repeated demonstration of a QTc interval \> 450 milliseconds, unless associated with the use of medications known to prolong the QTc interval). QTc will be calculated using the Bazett formula (RR interval = 60/heart rate; QTI corrected = QT interval/sqr\[RRinterval\])
• History of additional risk factors for torsade de pointes (e.g., heart failure, family history of long QT syndrome)
• Use of concomitant medications that increase or possibly increase the risk to prolong the QTc interval and/or induce torsades de pointes ventricular arrhythmia
• Females who are breastfeeding/lactating
• Known active infections (e.g., bacterial, fungal, viral including hepatitis and human immunodeficiency virus \[HIV\] positivity)
• Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study or compromise protocol objectives in the opinion of the investigator and/or the sponsor

Sponsors & Collaborators

• Jonsson Comprehensive Cancer Center: lead
• Mirati Therapeutics Inc.: collaborator
• Phase One Foundation: collaborator

Study Sites (1)

Rebecca Phelan

Los Angeles, California, 90095, United States

Location

MeSH Terms

Conditions

Rhabdomyosarcoma

Interventions

Vinorelbine; mocetinostat; benzamide

Condition Hierarchy (Ancestors)

Myosarcoma; Neoplasms, Muscle Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma

Intervention Hierarchy (Ancestors)

Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines

Study Officials

• Noah C. Federman, MD

  University of California at Los Angeles

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 10, 2020
• First Posted: March 6, 2020
• Study Start: May 14, 2020
• Primary Completion (Estimated): May 22, 2026
• Study Completion (Estimated): May 22, 2027
• Last Updated: June 26, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)