What side effects are associated with this type of intervention?

The most common treatments for Rhabdomyosarcoma, including vincristine, dactinomycin, cyclophosphamide, and doxorubicin, are associated with several side effects. Vincristine can cause peripheral neuropathy, constipation, and hair loss. Dactinomycin may lead to nausea, vomiting, and bone marrow suppression. Cyclophosphamide is known for causing hemorrhagic cystitis, myelosuppression, and an increased risk of secondary malignancies. Doxorubicin can result in cardiotoxicity, myelosuppression, and mucositis. These side effects vary in severity and frequency depending on the specific chemotherapy regimen and the individual patient's response.

What prior FDA approvals exist?

FDA-approved treatments for Rhabdomyosarcoma typically include multi-agent chemotherapy regimens. Commonly used drugs include vincristine, dactinomycin, and cyclophosphamide, often referred to as VAC therapy. These agents are used in various combinations and schedules to optimize treatment efficacy. The trial evaluating different chemotherapy schedules for Rhabdomyosarcoma is exploring similar strategies, aiming to determine the most effective timing and sequencing of these chemotherapeutic agents.

What other types of research exist?

Promising novel alternatives to traditional chemotherapy scheduling for rhabdomyosarcoma patients include adaptive timing strategies and combination therapies. The 'Evolutionary Therapy for Rhabdomyosarcoma' trial evaluates four different strategies: first strike therapy, first strike-second strike (maintenance) therapy, adaptively timed therapy, and conventional chemotherapy. These approaches aim to enhance treatment effectiveness and reduce resistance.

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Anti-tumor antibiotic

Chemotherapy for Rhabdomyosarcoma

Phase 2

Recruiting

Led By Jonathan MEtts, MD

Research Sponsored by H. Lee Moffitt Cancer Center and Research Institute

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

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

Must not have

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

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

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing four different chemotherapy schedules for patients with a specific type of advanced cancer. The goal is to find the best way to treat the disease by comparing different timing and combinations of chemotherapy treatments.

Who is the study for?

This trial is for individuals newly diagnosed with metastatic Fusion Positive Rhabdomyosarcoma. They must have tissue available for testing, no prior chemotherapy, and molecular confirmation of PAX/FOXO1 fusion. Participants need to agree to contraception use if applicable and be able to take oral medications if in Arm B. Pregnant or breastfeeding women are excluded.

What is being tested?

The study tests four chemotherapy strategies on Rhabdomyosarcoma: a first strike therapy (Arm A), a maintenance therapy after initial treatment (Arm B), an adaptively timed therapy based on disease response (Arm C), and conventional chemotherapy (Arm D). Patients choose their treatment arm with their physician.

What are the potential side effects?

Chemotherapy drugs like Actinomycin D, Cyclophosphamide, Vinorelbine, and Vincristine can cause side effects including nausea, hair loss, fatigue, increased risk of infection due to lowered blood cell counts, mouth sores, and potential damage to organs such as the heart or kidneys.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have been newly diagnosed with rhabdomyosarcoma.

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My cancer has a confirmed PAX/FOXO1 fusion.

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I have not had chemotherapy before.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I do not have any severe illnesses or social situations that would prevent me from following the study's requirements.

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My cancer has not spread only to nearby lymph nodes.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 5 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Adaptive Therapy Event Free Survival

First Strike Event Free Survival

Second Strike Event Free Survival

Secondary study objectives

Overall Survival

Treatment-related adverse events of a certain grade or higher

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

4Treatment groups

Experimental Treatment

Active Control

Group I: Arm C - Adaptive TherapyExperimental Treatment3 Interventions

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

Group II: Arm B - Second Strike - MaintenanceExperimental Treatment5 Interventions

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

Group III: Arm A - First StrikeExperimental Treatment3 Interventions

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

Group IV: Arm - D Conventional TherapyActive Control3 Interventions

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

First Studied

Drug Approval Stage

How many patients have taken this drug

Vincristine

2003

Completed Phase 4

~2970

Cyclophosphamide

2010

Completed Phase 4

~2310

Vinorelbine

2013

Completed Phase 4

~2190

0 / 5Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Rhabdomyosarcoma include chemotherapeutic agents like doxorubicin, cisplatin, and ifosfamide. Doxorubicin works by intercalating DNA, thereby inhibiting the replication of cancer cells and inducing apoptosis. Cisplatin forms DNA crosslinks, which prevent DNA replication and transcription, leading to cell death. Ifosfamide is an alkylating agent that causes DNA damage by adding alkyl groups to the DNA molecule, resulting in apoptosis. These mechanisms are crucial for Rhabdomyosarcoma patients as they target rapidly dividing cancer cells, aiming to reduce tumor size and prevent metastasis. The effectiveness of these treatments can vary based on the timing and scheduling of administration, which is why clinical trials are exploring optimal chemotherapy schedules to improve patient outcomes.

Cisplatin and doxorubicin for locally recurrent and metastatic childhood rhabdomyosarcoma.