Multimodal Therapy for Rhabdomyosarcoma

Recruiting in Palo Alto (17 mi)

+3 other locations

Overseen byMatthew J Krasin, MD

Age: < 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: St. Jude Children's Research Hospital

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?This study will treat participants with newly diagnosed, low, intermediate and high risk rhabdomyosarcoma (RMS) using multi-modality risk-adapted therapy with standard or intensified dose chemotherapy, radiation and surgical resection. Intermediate and high risk participants will receive an additional 12 weeks (4 cycles) of maintenance therapy with anti-angiogenic chemotherapy. PRIMARY OBJECTIVE: * Estimate event-free survival for intermediate risk participants treated with vincristine, dactinomycin and cyclophosphamide with the addition of maintenance anti-angiogenic therapy. SECONDARY OBJECTIVES: * Estimate the false negative rate and incidence of additional positive lymph nodes in participants undergoing sentinel lymph node biopsy followed by limited nodal dissection. * Maintain a high local control rate in participants treated with surgery and/or limited volume proton and photon radiation without dose escalation. * Define the incidence and type of failure in participants who receive risk-adapted local therapy relative to the primary tumor volume. * Establish the feasibility of delivering 4 cycles of maintenance anti-angiogenic chemotherapy in intermediate and high risk patients following standard chemotherapy. * Estimate the event free survival for high risk patients receiving interval dose compressed therapy and maintenance anti-angiogenic therapy. * Define the incidence of CTC grade 3 and higher toxicities (and specific grade 1-2 toxicities) related to proton beam therapy.

Eligibility Criteria

This trial is for children and young adults under 22 with newly diagnosed rhabdomyosarcoma (RMS), a type of muscle cancer. They must have low, intermediate, or high-risk disease levels, be able to start chemotherapy within 6 weeks after diagnosis, and have good organ function. Pregnant or breastfeeding individuals can't join.

Inclusion Criteria

All participants and/or their parents or legal guardians must sign a written informed consent

I am starting chemotherapy within 6 weeks after my biopsy or surgery.

My bone marrow is working well.

+10 more

Exclusion Criteria

Participants who fail to meet one or more of the inclusion criteria

I am scheduled for initial surgery to remove my cancer.

History of allergy to Optison(TM) contrast agent or blood products

Participant Groups

The study tests risk-adapted therapy using standard/intensified chemo, radiation, surgery for RMS patients. It aims to improve survival rates in intermediate/high-risk groups by adding maintenance anti-angiogenic therapy after initial treatment.

4Treatment groups

Experimental Treatment

Group I: Low-Risk, Subset 2Experimental Treatment7 Interventions

Lymph node sampling will take place pretreatment and pre-surgery. Participants receive 12 weeks of chemotherapy (vincristine, dactinomycin, cyclophosphamide). The tumor is evaluated to determine how it responded to treatment. Radiation therapy and/or surgical resection is performed to destroy or remove the remaining tumor. Twelve additional weeks of chemotherapy (vincristine, dactinomycin, cyclophosphamide) is given, followed by evaluation for tumor response. If delayed for medical reasons, radiation therapy and/or surgical resection is done at this time. Participants then receive 16 weeks of additional chemotherapy (vincristine, dactinomycin and cyclophosphamide). No further treatment is given, and participants are observed closely. Myeloid growth factor will be given if needed. Participants also receive \^1\^1C-methionine as described in the intervention section.

Group II: Low-Risk, Subset 1Experimental Treatment8 Interventions

Lymph node sampling will take place pretreatment and pre-surgery. Participants receive 12 weeks of chemotherapy (vincristine, dactinomycin and cyclophosphamide). They are then evaluated to determine how the tumor responded to treatment. Twelve additional weeks of chemotherapy (vincristine and dactinomycin) is given, followed by evaluation for tumor response. No further treatment is given, and participants are observed closely. Myeloid growth factor is given if needed. Participants also receive \^1\^1C-methionine as described in the intervention section.

Group III: Intermediate-RiskExperimental Treatment10 Interventions

Lymph node sampling takes place pretreatment and pre-surgery. Participants receive 12 weeks of chemotherapy (vincristine, dactinomycin, cyclophosphamide). The tumor is evaluated for treatment response. Radiation therapy and/or surgical resection is done. Twelve weeks of chemotherapy (vincristine, dactinomycin, cyclophosphamide) is followed by evaluation for tumor response. If delayed for medical reasons, radiation therapy and/or surgical resection is done at this time. Participants receive 16 weeks of chemotherapy (vincristine, dactinomycin, cyclophosphamide) followed by 12 weeks of maintenance treatment (bevacizumab, sorafenib, oral cyclophosphamide). No further treatment is given, and participants are observed closely. Myeloid growth factor is given if needed. Participants also receive \^1\^1C-methionine as described in the intervention section.

Group IV: High-RiskExperimental Treatment16 Interventions

Lymph node sampling takes place pretreatment and pre-surgery. Participants receive 6 weeks (2 cycles) chemotherapy (vincristine and irinotecan). The tumor is evaluated for treatment response. 3 cycles of chemotherapy \[vincristine, doxorubicin, cyclophosphamide/ifosfamide, etoposide (or etoposide phosphate) (VDC/IE)\] are given. Dexrazoxane is given prior to each dose of doxorubicin. Radiation therapy begins at week 4 or 20 (depending on tumor location) while receiving vincristine and irinotecan. 2 cycles of VDC/IE, 4 cycles of modified vincristine, dactinomycin, cyclophosphamide (VAC), then 2 cycles of modified vincristine/irinotecan (total of 54 weeks). High risk participants also receive additional maintenance therapy beginning week 55 with anti-angiogenic chemotherapy (bevacizumab, sorafenib, cyclophosphamide). Myeloid growth factor is given as needed. Participants also receive \^1\^1C-methionine as described in the intervention section.

Cyclophosphamide is already approved in United States, European Union, Canada, Japan for the following indications:

🇺🇸 Approved in United States as Cytoxan for: