What side effects are associated with this type of intervention?

The common treatments for Alveolar Rhabdomyosarcoma, such as vincristine and dactinomycin, have several known side effects. Vincristine often causes peripheral neuropathy, constipation, and hair loss. Dactinomycin typically results in nausea, vomiting, diarrhea, and myelosuppression. Both drugs can also lead to fatigue and an increased risk of infections due to their effects on the immune system.

What prior FDA approvals exist?

Vincristine and dactinomycin are commonly used in the treatment of rhabdomyosarcoma, including alveolar rhabdomyosarcoma. Vincristine works by inhibiting microtubule formation, which is essential for cell division, while dactinomycin inhibits DNA synthesis. These drugs have been part of standard chemotherapy regimens for rhabdomyosarcoma and have shown efficacy in various clinical trials. The combination of these agents aims to reduce tumor growth and improve patient outcomes by targeting different mechanisms of cancer cell proliferation.

What other types of research exist?

Promising novel alternatives to vincristine and dactinomycin for Alveolar Rhabdomyosarcoma patients include targeted therapies and immunotherapies. Specifically, kinase inhibitors such as selpercatinib or pralsetinib for RET-mutated tumors, and cabozantinib or vandetanib for non-RET mutated tumors, are suggested. These therapies offer potential for long-term disease stabilization and delay progression, although complete responses are uncommon. Additionally, the use of molecular risk stratification and therapy intensification based on DNA mutations is being explored to improve outcomes.

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Alkylating agents

Chemotherapy for Rhabdomyosarcoma

Phase 3

Recruiting

Led By Josephine H Haduong

Research Sponsored by Children's Oncology Group

Eligibility Criteria Checklist

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

Must have

Patients must be =< 21 years at the time of enrollment

Patients must have a Lansky (for patients =< 16 years of age) or Karnofsky (for patients > 16 years of age) performance status score of >= 50

Must not have

Patients who have received prior chemotherapy and/or radiation therapy for cancer prior to enrollment. Surgical resection alone of previous cancer(s) is permitted

Female patients who are pregnant

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

This trial uses chemotherapy drugs to treat patients with very low-risk and low-risk rhabdomyosarcoma. The goal is to maintain good outcomes while reducing treatment intensity. The study also examines if patients with specific DNA mutations benefit from more intensive therapy.

Who is the study for?

This trial is for patients up to 21 years old with newly diagnosed very low-risk or low-risk rhabdomyosarcoma, a type of soft tissue cancer. They must have specific stages and groups of the disease, proper organ function, no prior cancer treatments except surgery, and not be on certain drugs that affect vincristine.

What is being tested?

The study tests a chemotherapy regimen using vincristine and dactinomycin over 24 weeks for very low-risk patients. It also assesses standard chemo effectiveness in low-risk patients and intensifies therapy for those with DNA mutations to improve outcomes.

What are the potential side effects?

Possible side effects include hair loss, nausea, vomiting, mouth sores from chemotherapy; potential nerve damage from vincristine; skin changes or fatigue due to radiation therapy; increased risk of infection; and blood count changes.

Eligibility Criteria

Inclusion Criteria

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

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I am 21 years old or younger.

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I can do most activities but need help with some, regardless of my age.

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I have been newly diagnosed with a specific type of muscle cancer.

Exclusion Criteria

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

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I've had chemotherapy or radiation before for cancer, but surgery was only for removing it.

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I am currently pregnant.

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I cannot have radiation therapy if needed.

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I have an infection that is not responding to treatment.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 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

Failure free survival (FFS) for low risk patients

Failure free survival (FFS) for very low risk patients

Secondary study objectives

Feasibility of central molecular risk stratification of patients assessed by the percentage of patients who have molecular testing results returned by 6 weeks

Overall survival (OS) for low risk patients

Overall survival (OS) for very low risk patients

Other study objectives

Descriptive analysis of patients treated on Regimen M

Methylation array profile of patients with fusion negative, low-risk rhabdomyosarcoma

Awards & Highlights

No Placebo-Only Group

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

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

3Treatment groups

Experimental Treatment

Group I: Regimen VAC/VA (VL RMS)Experimental Treatment8 Interventions

Patients with LR RMS receive vincristine IV on day 1 of each cycle and days 8 and 15 of cycles 1-3. Patients also receive dactinomycin IV over 1-5 minutes or 10-15 minutes and cyclophosphamide IV over 60 minutes on day 1 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive vincristine IV on day 1 of each cycle and days 8 and 15 of cycles 5-7 and dactinomycin IV over 1-5 minutes or over 10-15 minutes on day 1 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients with MYOD1 or TP53 mutated tumors transition to Regimen M at cycle 2 (if mutation status is determined to be positive at week 3) or cycle 3 (if mutation status is determined to be positive after week 3). Radiation therapy (if needed) will be administered at cycle 5.Patients undergo CT scan, MRI, bone scan, PET scan and tumor biopsy throughout the study.

Group II: Regimen VA (VLR RMS)Experimental Treatment6 Interventions

Patients with VLR RMS receive vincristine intravenously (IV) on day 1 of each cycle and days 8 and 15 of cycles 1, 3, 5, and 7 and dactinomycin IV over 1-5 minutes or over 10-15 minutes on day 1 of each cycle. Treatment repeats every 21 days for 8 cycles in the absence of disease progression or unacceptable toxicity. Patients with MYOD1 or TP53 mutated tumors transition to Regimen M at cycle 2 (if mutation status is determined to be positive at week 3) or cycle 3 (if mutation status is determined to be positive after week 3). Patients undergo CT scan, MRI, bone scan, PET scan and tumor biopsy throughout the study.

Group III: Regimen M (positive mutation)Experimental Treatment9 Interventions

Patients receive vincristine IV on day 1 of each cycle and days 8 and 15 of cycles 2-4, 7-8, and 11-12 and dactinomycin IV over 1-5 minutes or 10-15 minutes on day 1 of cycles 2-5 and 8-14. Patients also receive cyclophosphamide IV over 60 minutes on day 1 of each cycle. Treatment repeats every 21 days for 12-13 cycles in the absence of disease progression or unacceptable toxicity. Patients may also undergo radiation therapy at cycle 5. Patients undergo CT scan, MRI, bone scan, PET scan and tumor biopsy throughout the study.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Biopsy

2014

Completed Phase 4

~1150

Bone Scan

2015

Completed Phase 2

~50

Computed Tomography

2017

Completed Phase 2

~2790

Cyclophosphamide

2010

Completed Phase 4

~2310

Dactinomycin

2010

Completed Phase 3

~1310

Positron Emission Tomography

2011

Completed Phase 2

~2200

Radiation Therapy

2017

Completed Phase 3

~7250

Vincristine

2003

Completed Phase 4

~2970

0 / 7Eligibility 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

Vincristine and dactinomycin are commonly used treatments for Alveolar Rhabdomyosarcoma (ARMS). Vincristine inhibits microtubule formation, which is essential for cell division, thereby halting the mitotic process and leading to cell death. Dactinomycin intercalates into DNA and inhibits RNA synthesis, preventing the transcription necessary for protein synthesis and cell survival. These mechanisms are crucial for ARMS patients as they target the rapid and uncontrolled cell division characteristic of this cancer, potentially improving treatment outcomes.

Variable duration of vincristine-induced metaphase block in leukemic and nornal bone marrow cells of children.Evaluation of ABT-751 against childhood cancer models in vivo.