Evolutionary Therapy for Rhabdomyosarcoma

H. Lee Moffitt Cancer Center and Research Institute

Status and phase: Active, not recruiting; Phase 2

Conditions: Rhabdomyosarcoma

Treatments: Drug: Actinomycin D; Drug: Cyclophosphamide; Drug: Vinorelbine; Drug: Cyclophosphamide Pill; Drug: Vincristine

Study type: Interventional

Funder types: Other

Identifiers

NCT04388839

MCC-20339

Details and patient eligibility

About

This clinical trial will evaluate 4 different strategies of chemotherapy schedules in newly diagnosed participants with metastatic Fusion Positive (alveolar) Rhabdomyosarcoma. The participant and their physician will choose from: Arm A) a first strike therapy, Arm B) a first strike-second strike (maintenance) therapy, Arm C) an adaptively timed therapy, and Arm D) conventional chemotherapy.

Enrollment: 12 patients

Sex: All

Volunteers: No Healthy Volunteers

Inclusion criteria

• Participants must have a new histologic diagnosis of rhabdomyosarcoma
• Participants must have FISH, PCR or other molecular confirmation of PAX/FOXO1 fusion per institutional standards
• Participants must have sufficient tissue (up to 10 unstained FFPE) for correlative testing
• All participants must have distant metastatic disease; either biopsy positive or PET avid extranodal or distant nodal lesions determined by the investigator to be metastatic disease. Patients with a single distant metastatic site that has been excised prior to study entry are eligible
• No prior systemic chemotherapy
• Participants enrolled to Arm B, maintenance, must be able to take oral cyclophosphamide. Note: enteral administration of cyclophosphamide is allowable.
• Males and females of reproductive potential may not participate unless they have agreed to the use of, at minimum, two methods of contraception during and after treatment or abstinence.
• Women of childbearing potential should adhere to contraception for a period of 4 months after completion of systematic chemotherapy administration
• Men who are sexually active with women of child bearing potential should adhere to contraception for a period of 4 months after completion of systematic chemotherapy administration
• All patients and/or their parents or legal guardians must have the ability to understand and the willingness to sign a written informed consent or assent document.

Exclusion criteria

• Participants with regional lymph nodes as the only site of disease are not eligible. Distant nodal sites alone are eligible

• Participants who are receiving any other investigational agents for rhabdomyosarcoma are ineligible

• Participants must not be receiving any additional medicines being given for the specific purpose of treating cancer. Alternative medications including, but not limited to cannabis based products would not be a reason for exclusion

• Participants are ineligible if they have uncontrolled intercurrent illness including, but not limited to:

  • ongoing or active infection not expected to resolve with current antibiotic plan
  • cardiac arrhythmia
  • psychiatric illness/social situations that would limit compliance with study requirements

• Patients who are pregnant or breastfeeding are not eligible because there is no available information regarding human fetal or teratogenic toxicities. Females of childbearing potential must have a negative serum or urine pregnancy test within 24 hours of starting protocol therapy.

• Participants who are considered unable to comply with the safety monitoring requirements of the study are not eligible

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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12 participants in 4 patient groups

Arm A - First Strike

Experimental group

Description:

Participants will receive 42 weeks of conventional doses of vinorelbine, actinomycin D and cyclophosphamide

Treatment:

Drug: Vinorelbine

Drug: Cyclophosphamide

Drug: Actinomycin D

Arm B - Second Strike - Maintenance

Experimental group

Description:

Participants will receive conventional doses of Vincristine/Actinomycin D/Cyclophosphamide (VAC) until complete response (CR) for 12-42 weeks and then switch to up to 2 years of vinorelbine/oral cyclophoshamide

Treatment:

Drug: Vincristine

Drug: Cyclophosphamide Pill

Drug: Vinorelbine

Drug: Cyclophosphamide

Drug: Actinomycin D

Arm C - Adaptive Therapy

Experimental group

Description:

Therapy with VAC that starts and stops based on response, adaptive timing of therapy, with a prolonged time to progression rather than complete remission goal

Treatment:

Drug: Vincristine

Drug: Cyclophosphamide

Drug: Actinomycin D

Arm - D Conventional Therapy

Active Comparator group

Description:

Participants will receive a chemotherapy combination based on published trials. An example would be 42 weeks of VAC but may also include irinotecan, doxorubicin, ifosfamide, etoposide.

Treatment:

Drug: Vincristine

Drug: Cyclophosphamide

Drug: Actinomycin D