What is the mechanism of action of this treatment?

The most common treatments for Rhabdomyosarcoma include vincristine sulfate, dactinomycin, cyclophosphamide, irinotecan hydrochloride, vinorelbine, and temsirolimus. These drugs work by either killing tumor cells, stopping them from dividing, or preventing them from spreading. Temsirolimus specifically blocks enzymes needed for cell growth, which is crucial for halting the proliferation of cancer cells. Understanding these mechanisms is important for Rhabdomyosarcoma patients as it aids in selecting the most effective treatment strategy and managing expectations regarding treatment outcomes.

What side effects are associated with this type of intervention?

Common treatments for rhabdomyosarcoma, including chemotherapy drugs like vincristine, dactinomycin, and cyclophosphamide, often cause side effects such as nausea, vomiting, hair loss, fatigue, and increased infection risk due to bone marrow suppression. Enzyme inhibitors like temsirolimus, which block enzymes needed for cell growth, can cause mouth sores, rash, fatigue, and increased blood sugar levels. Combining these treatments may amplify these effects.

What prior FDA approvals exist?

The FDA has approved various treatments for rhabdomyosarcoma, primarily focusing on combination chemotherapy regimens. These typically include drugs like vincristine sulfate, dactinomycin, and cyclophosphamide. While temsirolimus, which blocks enzymes needed for cell growth, is being studied, other similar enzyme-blocking drugs like tyrosine kinase inhibitors have not been specifically mentioned for rhabdomyosarcoma in the provided context. Therefore, the focus remains on traditional chemotherapy combinations.

What other types of research exist?

Promising novel alternatives to Temsirolimus for Rhabdomyosarcoma patients include Sorafenib and Everolimus, which have been studied in phase 2 clinical trials for high-grade osteosarcoma, and Pembrolizumab, which has shown efficacy in advanced soft-tissue sarcoma. These therapies target different pathways involved in tumor growth and have shown potential in clinical settings.

← Back to Search

Alkylating agents

Chemotherapy +/− Temsirolimus for Muscle Cancer

Phase 3

Waitlist Available

Led By Abha A Gupta

Research Sponsored by National Cancer Institute (NCI)

Eligibility Criteria Checklist

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

Must have

Patients must be < 21 years of age at the time of enrollment for the Feasibility Phase

Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/gender

Must not have

Patients who have received any chemotherapy (excluding steroids) and/or RT prior to this enrollment

Patients with uncontrolled hyperglycemia

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 10 years

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

This trial is testing if adding the drug temsirolimus to standard chemotherapy is more effective for treating children and young adults with a type of muscle cancer that has a moderate chance of coming back. The chemotherapy drugs aim to kill or stop the growth of cancer cells, while temsirolimus may help by blocking certain enzymes needed for cancer growth.

Who is the study for?

This trial is for patients under 40 with newly diagnosed Rhabdomyosarcoma (RMS), a type of muscle tissue cancer, who haven't had previous chemotherapy or radiation. They must have an acceptable level of blood cells and kidney function, and be able to perform daily activities at least half the time. Pregnant women, breastfeeding mothers, those with uncontrolled diabetes or cholesterol levels, and individuals not using effective contraception are excluded.

What is being tested?

The study compares standard combination chemotherapy (including vincristine sulfate, dactinomycin, cyclophosphamide) alternated with other drugs like irinotecan hydrochloride or vinorelbine against the same chemotherapy plus temsirolimus. The goal is to see if adding temsirolimus better stops RMS from growing by blocking enzymes needed for cell growth.

What are the potential side effects?

Chemotherapy can cause side effects such as nausea, hair loss, fatigue, increased risk of infection due to low blood counts. Temsirolimus may add risks like mouth sores, rash, high blood sugar levels and lung problems. Each patient's experience can vary.

Eligibility Criteria

Inclusion Criteria

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

Select...

I am under 21 years old.

Select...

My kidney function is normal or near normal.

Select...

My bilirubin levels are within the normal range for my age.

Select...

I have enough tissue samples for the study.

Select...

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

Select...

I am 40 years old or younger.

Exclusion Criteria

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

Select...

I have had chemotherapy or radiation therapy before joining this study.

Select...

My blood sugar levels are not under control.

Select...

I have not taken temsirolimus, other mTOR inhibitors, or experimental drugs.

Select...

I am not pregnant.

Select...

My cholesterol levels are not under control.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 10 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 10 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 10 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

Event-free Survival (EFS)

Secondary study objectives

Overall Survival (OS)

Other study objectives

Frequency of Circulating Tumor DNA (ctDNA) at Diagnosis and Subsequent Time-points

Patient Outcome Based on Their [F18]-Fluorodeoxy-D-glucose-positron Emission Tomography (FDG-positron Emission Tomography [PET]) Response

Patient Outcomes Based on (Vincristine, Dactinomycin, and Cyclophosphamide [VAC]/Vincristine and Irinotecan [VI] With or Without Temsirolimus) Who Have Received Maintenance Therapy on ARST1431 to Those Who Received VAC/VI on ARST0531

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 C (FOXO1 fusion negative, VAC/VA)Experimental Treatment6 Interventions

Patients receive vincristine sulfate IV over 1 minute on day 1 of weeks 1-10 and 13-22, dactinomycin IV over 1-5 or 10-15 minutes on day 1 of weeks 1, 4, 7, 10, 13, 16, 19, and 22, cyclophosphamide IV over 60 minutes on day 1 of weeks 1, 4, 7, and 10. Patients undergo RT beginning at week 13 for up to 6.5 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.

Group II: Regimen B (VAC/VI/temsirolimus)Experimental Treatment9 Interventions

Patients receive vincristine sulfate IV over 1 minute on day 1 of weeks 1-13, 16, 17, 19, 20, 22-26, 28, 31-34, 37, 38, and 40, dactinomycin IV over 1-5 or 10-15 minutes on day 1 of weeks 1, 7, 13, 22, 28, 34, and 40, cyclophosphamide IV over 60 minutes on day 1 of weeks 1, 7, 13, 22, 28, 34, and 40, irinotecan hydrochloride IV over 90 minutes on days 1-5 of weeks 4, 10, 16, 19, 25, 31, and 37 and temsirolimus IV over 30-60 minutes on day 1 of weeks 1-12 and 21-42. Patients also undergo RT as in Regimen A. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients then receive vinorelbine IV over 6-10 minutes on days 1, 8, and 15 and cyclophosphamide PO QD on days 1-28. Cycles repeats every 28 days for 24 weeks in the absence of disease progression or unacceptable toxicity.

Group III: Regimen A (VAC/VI)Experimental Treatment7 Interventions

Patients receive vincristine sulfate IV over 1 minute on day 1 of weeks 1-13, 16, 17, 19, 20, 22-26, 28, 31-34, 37, 38, and 40, dactinomycin IV over 1-5 or 10-15 minutes on day 1 of weeks 1, 7, 13, 22, 28, 34, and 40, cyclophosphamide IV over 60 minutes on day 1 of weeks 1, 7, 13, 22, 28, 34, and 40, irinotecan hydrochloride IV over 90 minutes on days 1-5 of weeks 4, 10, 16, 19, 25, 31, and 37. Patients also undergo primary site RT beginning at week 13 or metastatic site RT beginning at week 43 for up to 6.5 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients then receive vinorelbine IV over 6-10 minutes on days 1, 8, and 15 and cyclophosphamide PO QD on days 1-28. Cycles repeats every 28 days for 24 weeks in the absence of disease progression or unacceptable toxicity.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Cyclophosphamide

2010

Completed Phase 4

~2310

Dactinomycin

2010

Completed Phase 3

~1310

Radiation Therapy

2017

Completed Phase 3

~7250

Vinorelbine

2013

Completed Phase 4

~2190

Irinotecan Hydrochloride

2010

Completed Phase 3

~2050

Temsirolimus

2008

Completed Phase 2

~1940

Vincristine Sulfate

2005

Completed Phase 3

~10270

0 / 11Eligibility 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 vincristine sulfate, dactinomycin, cyclophosphamide, irinotecan hydrochloride, vinorelbine, and temsirolimus. These drugs work by either killing tumor cells, stopping them from dividing, or preventing them from spreading. Temsirolimus specifically blocks enzymes needed for cell growth, which is crucial for halting the proliferation of cancer cells. Understanding these mechanisms is important for Rhabdomyosarcoma patients as it aids in selecting the most effective treatment strategy and managing expectations regarding treatment outcomes.