Multimodal Therapy for Rhabdomyosarcoma

Not currently recruiting at 3 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: St. Jude Children's Research Hospital

Disqualifiers: Pregnancy, Uncontrolled infection, Allergy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of treatments for individuals newly diagnosed with rhabdomyosarcoma (RMS), a cancer that develops in soft tissue. It evaluates the effectiveness of varying levels of chemotherapy, radiation, and surgery, with some groups receiving additional anti-angiogenic therapy to improve outcomes. The trial aims to identify the best treatment approach for low, intermediate, and high-risk cases. It is suitable for individuals under 22 years old who have not yet received treatment for RMS but have had a biopsy or surgery to confirm the diagnosis. Participants must begin chemotherapy within six weeks of diagnosis. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the treatments used in this trial have known safety records, but they can cause side effects.

Vincristine may lead to seizures and high blood pressure in some people, so patients will be monitored for these issues. Dactinomycin is very strong and must be handled carefully because it can harm soft tissues. Cyclophosphamide can cause severe nausea and vomiting and may increase the risk of infections. It is also linked to long-term risks like developing other cancers later on. Bevacizumab might cause high blood pressure and should be used carefully in people with existing health conditions. Proton beam radiation is generally considered safe for treating rhabdomyosarcoma, with studies showing fewer immediate and long-term side effects compared to other types of radiation.

Despite potential side effects, these treatments are used for their effectiveness against cancer. All participants will be closely monitored to manage any side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for rhabdomyosarcoma because they use a multimodal approach that combines chemotherapy, proton beam radiation, and maintenance therapy to target tumors more effectively. Unlike traditional treatments that might rely on a single type of therapy, this approach uses a combination of drugs like vincristine, dactinomycin, and cyclophosphamide, along with innovative proton beam radiation, which can precisely target tumors while minimizing damage to surrounding healthy tissue. Additionally, the introduction of maintenance therapy with anti-angiogenic agents like bevacizumab and sorafenib offers a new strategy to prevent tumor growth by cutting off its blood supply. This comprehensive strategy could potentially improve outcomes for patients with different risk levels of rhabdomyosarcoma.

What evidence suggests that this trial's treatments could be effective for rhabdomyosarcoma?

Research has shown that a combination of three drugs—vincristine, dactinomycin, and cyclophosphamide (VAC)—effectively treats rhabdomyosarcoma (RMS), a type of cancer. This trial will test the VAC combination in different treatment arms. For patients with an intermediate risk level, VAC treatment has been linked to better survival rates compared to some other treatments. Additionally, the trial is testing bevacizumab, a drug that can block the blood supply to tumors, in the high-risk treatment arm. While its effectiveness for RMS is still under study, some reports suggest it might help slow tumor growth in certain cases. Overall, current evidence supports using these treatments to improve outcomes for RMS patients. ^{5 6 7 8 9}

Who Is on the Research Team?

Matthew J Krasin, MD

Principal Investigator

St. Jude Children's Research Hospital

Are You a Good Fit for This Trial?

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.

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemotherapy

Participants receive chemotherapy based on their risk group. Low-risk participants receive 12 weeks of chemotherapy, intermediate-risk participants receive 12 weeks followed by 16 weeks of additional chemotherapy, and high-risk participants receive 6 weeks of initial chemotherapy followed by additional cycles.

12-54 weeks

Radiation and/or Surgery

Participants undergo radiation therapy and/or surgical resection based on their risk group and treatment response.

Varies

Maintenance Therapy

Intermediate and high-risk participants receive maintenance therapy with anti-angiogenic chemotherapy.

12-16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment. This includes monitoring for event-free survival and incidence of toxicities.

2-5 years

What Are the Treatments Tested in This Trial?

Interventions

• Bevacizumab
• Cyclophosphamide
• Dactinomycin
• Proton Beam Radiation
• Surgical Resection
• Vincristine

Trial Overview

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.

How Is the Trial Designed?

Group I: Low-Risk, Subset 2 Experimental Treatment 7 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 1 Experimental Treatment 8 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-Risk Experimental Treatment 10 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-Risk Experimental Treatment 16 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:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in European Union as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Canada as Neosar for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Japan as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma

Who Is Running the Clinical Trial?

St. Jude Children's Research Hospital

Lead Sponsor

Trials

451

Recruited

5,326,000+

Published Research Related to This Trial

In a study using a laboratory model of childhood rhabdomyosarcoma (RMS) with seven patient-derived xenografts, the conventional chemotherapy agent vincristine was found to be the most effective treatment.

L-phenylalanine mustard (L-PAM) showed remarkable efficacy, causing complete tumor regressions in six out of seven RMS lines, including those resistant to cyclophosphamide, indicating its potential as a powerful treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Childhood rhabdomyosarcoma xenografts: responses to DNA-interacting agents and agents used in current clinical therapy. Houghton, JA., Cook, RL., Lutz, PJ., et al.[2019]

In a clinical trial involving 92 children with rhabdomyosarcoma, both high single doses and divided doses of dactinomycin (ACT-D) combined with vincristine and cyclophosphamide showed similar effectiveness, with major response rates of 67% and 70%, respectively.

The study found that administering high, single doses of ACT-D resulted in low toxicity and did not increase adverse effects compared to the divided dosing, suggesting it is a feasible treatment option that requires less hospitalization for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor response and toxicity after single high-dose versus standard five-day divided-dose dactinomycin in childhood rhabdomyosarcoma. Carli, M., Pastore, G., Perilongo, G., et al.[2017]

With modern treatments, over 70% of children and adolescents with rhabdomyosarcoma can be cured, highlighting the importance of accurate diagnosis and multidisciplinary therapy for maximizing cure rates.

Current research is focusing on new therapies, including topoisomerase-I inhibitors and molecular characterization of tumors, which may lead to more effective treatments for high-risk patients who currently have poor outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rhabdomyosarcoma: new windows of opportunity. Breitfeld, PP., Meyer, WH.[2022]

In a clinical trial involving 271 patients with low-risk embryonal rhabdomyosarcoma, a shorter treatment regimen using lower-dose cyclophosphamide and radiotherapy achieved a 3-year failure-free survival rate of 89%, indicating effective treatment without compromising outcomes.

The study demonstrated that this modified therapy resulted in significantly fewer expected treatment failures (35 observed vs. 48.4 expected), suggesting that reducing treatment duration and dosage can maintain efficacy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Shorter-duration therapy using vincristine, dactinomycin, and lower-dose cyclophosphamide with or without radiotherapy for patients with newly diagnosed low-risk rhabdomyosarcoma: a report from the Soft Tissue Sarcoma Committee of the Children's Oncology Group. Walterhouse, DO., Pappo, AS., Meza, JL., et al.[2022]

The combination of temsirolimus with standard chemotherapy (VAC/VI) in children with intermediate-risk rhabdomyosarcoma was found to be feasible and well tolerated, with only 20% of patients experiencing dose-limiting toxicities.

Out of 10 patients treated, no treatment-related deaths occurred, and the regimen is currently being evaluated for its efficacy in a phase III trial against standard chemotherapy alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility of combining temsirolimus to vincristine, dactinomycin, cyclophosphamide, and vincristine and irinotecan chemotherapy for children with intermediate-risk rhabdomyosarcoma: A report from Children's Oncology Group. Oberoi, S., Qumseya, A., Xue, W., et al.[2023]

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