Chemotherapy +/− Temsirolimus for Muscle Cancer

Not currently recruiting at 438 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: National Cancer Institute (NCI)

Must not be taking: mTOR inhibitors

Disqualifiers: Previous chemotherapy, Uncontrolled hyperglycemia, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 31

Duration: 40 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether adding temsirolimus (an mTOR inhibitor) to standard chemotherapy improves treatment for rhabdomyosarcoma, a cancer that forms in muscles and soft tissues. The trial compares outcomes between patients receiving only chemotherapy and those receiving chemotherapy plus temsirolimus. It targets patients with intermediate-risk rhabdomyosarcoma, indicating a moderate chance of cancer recurrence after initial treatment. Newly diagnosed individuals with certain types of rhabdomyosarcoma who have not received prior chemotherapy may qualify to participate. The research aims to determine if temsirolimus can more effectively stop tumor growth. As a Phase 3 trial, this study represents the final step before FDA approval, offering patients a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial information 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 has shown that temsirolimus has been safely used in patients with kidney cancer. It is approved in the U.S. and other countries for this purpose, indicating a reasonable level of safety. However, earlier studies in patients with soft tissue sarcoma found that temsirolimus had moderate side effects. These studies provide insight into how the drug might affect patients with similar conditions.

The chemotherapy drugs involved in the trial, such as vincristine sulfate, dactinomycin, cyclophosphamide, and irinotecan hydrochloride, have long been used in cancer treatments. They are generally well-tolerated at the doses used in trials, though side effects like nausea, fatigue, and low blood counts can occur. Extensive research has provided a strong base of safety data for these treatments.

While specific safety data for the exact combination being tested in this trial is not available, the trial phase suggests some confidence in its safety. This indicates that the treatment has passed earlier testing stages and has shown enough safety to be tested on a larger scale. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for muscle cancer because they combine traditional chemotherapy drugs with temsirolimus, potentially enhancing effectiveness. Temsirolimus, a newer addition, inhibits a specific protein pathway (mTOR), which could stop cancer cells from growing and dividing. This targeted action differentiates it from standard chemotherapy, which generally affects both healthy and cancerous cells. Combining these mechanisms could lead to improved outcomes and fewer side effects compared to current treatments.

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

Research shows that adding temsirolimus to standard chemotherapy does not benefit patients with intermediate-risk rhabdomyosarcoma, a type of muscle cancer. In this trial, participants in Regimen B will receive chemotherapy drugs such as vincristine, dactinomycin, and cyclophosphamide, along with temsirolimus. Studies have found that these chemotherapy drugs effectively stop tumor growth by killing cancer cells or preventing their spread. However, including temsirolimus does not enhance the treatment's effectiveness. Previous trials showed no significant improvement in patient outcomes with temsirolimus. While the chemotherapy itself works well, temsirolimus does not enhance its efficacy for this specific condition. ^{1 6 7 8 9}

Who Is on the Research Team?

Abha A Gupta

Principal Investigator

Children's Oncology Group

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

I have a specific type of muscle cancer, not the adult-type pleomorphic kind.

My high creatinine levels are due to a tumor blocking my kidney.

My kidney function is normal or near normal.

Exclusion Criteria

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

Lactating females who plan to breastfeed their infants are not eligible

My blood sugar levels are not under control.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive combination chemotherapy with or without temsirolimus, including surgery and radiotherapy

40 weeks

Multiple visits for chemotherapy administration and radiotherapy

Maintenance

Participants receive vinorelbine and cyclophosphamide for maintenance therapy

24 weeks

Cycles repeat every 28 days for up to 6 cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 10 years

Every 3 months for 1 year, every 4 months for 2 years, every 6 months for 1 year, then annually

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• Dactinomycin
• Irinotecan Hydrochloride
• Radiation Therapy
• Temsirolimus
• Vincristine Sulfate
• Vinorelbine

Trial Overview

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.

How Is the Trial Designed?

Group I: Regimen C (FOXO1 fusion negative, VAC/VA) Experimental Treatment 6 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 Treatment 9 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 Treatment 7 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.

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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Vinorelbine (Navelbine) has shown significant antitumor activity in various cancers, including a 33% response rate in non-small cell lung cancer and a 53% response rate in advanced breast cancer, based on early phase II studies.

The drug primarily causes neutropenia as a side effect, with minimal neurotoxicity and manageable other side effects, making it a promising option for cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in vinca-alkaloids: Navelbine. Marty, M., Extra, JM., Espie, M., et al.[2018]

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]

Vinorelbine (Navelbine) demonstrated an overall response rate of 16% in heavily pretreated patients with advanced and/or metastatic breast cancer, with responses primarily observed in lymph nodes, breast tissue, and soft tissue.

The treatment was well-tolerated, with the most significant toxicities being granulocytopenia and anemia, affecting 51% and 9% of patients respectively, while other side effects were mild and rare.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vinorelbine (navelbine) as a salvage treatment for advanced breast cancer. Degardin, M., Bonneterre, J., Hecquet, B., et al.[2020]

The combination of cyclophosphamide, epirubicin, and vinorelbine (CEN) was administered to 56 patients with advanced breast cancer, resulting in a 50% objective response rate, with a median overall survival time of 90 weeks.

While the treatment showed acceptable tolerability, with manageable side effects like neutropenia and nausea, it did not demonstrate improved efficacy compared to other first-line treatments for advanced breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II trial of cyclophosphamide, epirubicin and vinorelbine in the treatment of advanced breast cancer. Esteban, E., de Sande, G., Puertas, J., et al.[2019]

Vinorelbine, an oral and intravenous chemotherapy drug, was found to have a maximum tolerated dose of 30 mg/m² in children without bone marrow involvement, with myelosuppression (reduced blood cell production) being the main side effect.

The study revealed that children metabolize vinorelbine differently than adults, showing higher plasma clearance and lower overall drug exposure, which may influence dosing strategies for pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I evaluation of oral and intravenous vinorelbine in pediatric cancer patients: a report from the Children's Oncology Group. Johansen, M., Kuttesch, J., Bleyer, WA., et al.[2018]

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Pfizer Reports Results From Phase 3 Study Of Torisel ...

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