Chemotherapy +/− Temsirolimus for Muscle Cancer

Recruiting at 414 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

325 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug vinorelbine in treating muscle cancer?

Vinorelbine has shown effectiveness in treating advanced breast cancer and non-small cell lung cancer, with studies indicating it can improve survival rates and has a manageable safety profile. While these results are from different types of cancer, they suggest potential benefits of vinorelbine in cancer treatment. ^{1 2 3 4 5}

What safety data exists for the treatment of muscle cancer with chemotherapy and Temsirolimus?

Vinorelbine, a drug used in chemotherapy, has been studied for its safety in humans. Common side effects include myelosuppression (a decrease in bone marrow activity), nausea, vomiting, and neuropathy (nerve damage). Irinotecan, another chemotherapy drug, can cause delayed diarrhea and neutropenia (low white blood cell count), with rare but serious side effects like liver and kidney issues. These drugs have been used in various cancers, and their side effects are generally manageable with proper medical care. ^{1 6 7 8 9}

What makes the chemotherapy treatment with temsirolimus unique for muscle cancer?

This treatment is unique because it combines temsirolimus, an mTOR inhibitor that has shown activity against rhabdomyosarcoma (a type of muscle cancer), with a standard chemotherapy regimen. This combination aims to enhance the anticancer effects by integrating temsirolimus with established drugs like vincristine, actinomycin-D, and cyclophosphamide, potentially offering a new approach for intermediate-risk muscle cancer. ^{1 10 11 12 13}

What is the purpose of this trial?

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.

Research Team

Abha A Gupta

Principal Investigator

Children's Oncology Group

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 (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]

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]

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]

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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

A phase II trial of cyclophosphamide, epirubicin and vinorelbine in the treatment of advanced breast cancer. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

A clinical phase II study of cisplatinum and vinorelbine (PVn) in advanced breast carcinoma (ABC). [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Vinorelbine (Navelbine)--a new agent for the treatment of non-small cell lung cancer: a summary. [2018]

4. France pubmed.ncbi.nlm.nih.gov

[Results of a randomized study comparing combination of navelbine-cisplatin to combination of vindesine-cisplatin and to navelbine alone in 612 patients with inoperable non-small cell lung cancer]. [2017]

5. England pubmed.ncbi.nlm.nih.gov

Vinorelbine (navelbine) as a salvage treatment for advanced breast cancer. [2020]

6. Germany pubmed.ncbi.nlm.nih.gov

Advances in vinca-alkaloids: Navelbine. [2018]

7. England pubmed.ncbi.nlm.nih.gov

Vinorelbine-related tetraplegia due to severe peripheral neuropathy. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Colorectal cancer: dilemmas regarding patient selection and toxicity prediction. [2018]

9. United States 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. [2018]

10. United States 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. [2023]

11. England pubmed.ncbi.nlm.nih.gov

Vinorelbine in breast cancer. [2019]

12. United States pubmed.ncbi.nlm.nih.gov

In vivo study of vinorelbine associations with cisplatin, 5-fluorouracil or actinomycin D relative to a non-small-cell lung carcinoma (NSCLCN6-L16). [2018]

13. United States pubmed.ncbi.nlm.nih.gov

A phase I trial of the mTOR inhibitor temsirolimus in combination with capecitabine in patients with advanced malignancies. [2021]