Chemotherapy for Rhabdomyosarcoma

Not currently recruiting at 19 trial locations

Overseen By Jessica Crimella, BSN, RN

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Must be taking: Cyclophosphamide

Must not be taking: Investigational agents

Disqualifiers: Pregnancy, Active infection, Cardiac arrhythmia, 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

Duration: 12-42 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores four different chemotherapy plans to treat metastatic Fusion Positive Rhabdomyosarcoma. Participants can choose from strategies such as a single strong treatment, a combination of initial and follow-up treatment, timing therapy based on response, or standard chemotherapy. It targets those newly diagnosed with this cancer, who have not yet received chemotherapy and show evidence of cancer spread. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications, but you cannot be on any other cancer treatments. Alternative medications like cannabis products are allowed.

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

Research shows that the treatments tested in this trial have varying safety levels. Here’s a simple overview:

Vinorelbine is usually safe and well-tolerated for outpatients, but it can lower white blood cell counts, making infection more likely.

Actinomycin D is very potent and requires careful use. It can cause serious side effects, including harm to unborn babies, and can reduce bone marrow activity, leading to fewer blood cells.

Cyclophosphamide has been linked to a higher risk of other cancers, infertility, and birth defects. High doses can also affect the heart.

Vincristine is used for various cancers, including rhabdomyosarcoma. It can cause tissue damage if it leaks from the vein and may increase infection risk when combined with other treatments.

While these treatments have known side effects, they are commonly used in cancer therapy. The trial's middle stage suggests that initial human testing has shown these treatments to be relatively safe, though side effects do exist. Participants should consider these risks and discuss them with their healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for rhabdomyosarcoma because they offer tailored approaches that could improve outcomes. Unlike standard chemotherapy, which typically follows a fixed schedule, the adaptive therapy in Arm C adjusts the timing of treatment based on how the cancer responds, aiming to prolong the time to progression instead of just seeking complete remission. Arm A and Arm B focus on strategic use of conventional drugs like vinorelbine, actinomycin D, and cyclophosphamide, but Arm B extends treatment with a maintenance phase that could provide prolonged benefits. These innovative strategies might offer more personalized and potentially more effective ways to manage rhabdomyosarcoma compared to traditional, one-size-fits-all treatment regimens.

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

Research has shown that vinorelbine, which participants in this trial may receive, can help treat alveolar rhabdomyosarcoma. Studies report a 41% increase in response rates for patients whose cancer has returned or is resistant to treatment. In this trial, some participants will receive a combination of actinomycin D, vincristine, and cyclophosphamide. Studies have found that this combination results in 63% of patients not experiencing cancer progression for three years, with 84% still alive after three years. Cyclophosphamide's effectiveness can depend on the dose, with higher doses sometimes leading to better results. Vincristine has improved outcomes when used with other treatments, increasing survival rates in some studies. Each of these drugs has shown potential for improving survival and response rates in patients with rhabdomyosarcoma. ^{6 7 8 9 10}

Who Is on the Research Team?

Jonathan Metts, MD

Principal Investigator

Moffitt Cancer Center

Are You a Good Fit for This Trial?

This trial is for individuals newly diagnosed with metastatic Fusion Positive Rhabdomyosarcoma. They must have tissue available for testing, no prior chemotherapy, and molecular confirmation of PAX/FOXO1 fusion. Participants need to agree to contraception use if applicable and be able to take oral medications if in Arm B. Pregnant or breastfeeding women are excluded.

Inclusion Criteria

My cancer has spread to distant parts of my body, confirmed by tests.

I have been newly diagnosed with rhabdomyosarcoma.

I will use contraception for 4 months after my chemotherapy ends.

Exclusion Criteria

I do not have any severe illnesses or social situations that would prevent me from following the study's requirements.

Participants who are considered unable to comply with the safety monitoring requirements of the study are not eligible

Patients who are pregnant or breastfeeding are not eligible because there is no available information regarding human fetal or teratogenic toxicities. Females of childbearing potential must have a negative serum or urine pregnancy test within 24 hours of starting protocol therapy

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive chemotherapy based on chosen strategy: first strike, first strike-second strike (maintenance), adaptively timed, or conventional chemotherapy

12-42 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

3-5 years

What Are the Treatments Tested in This Trial?

Interventions

• Actinomycin D
• Cyclophosphamide
• Cyclophosphamide Pill
• Vincristine
• Vinorelbine

Trial Overview The study tests four chemotherapy strategies on Rhabdomyosarcoma: a first strike therapy (Arm A), a maintenance therapy after initial treatment (Arm B), an adaptively timed therapy based on disease response (Arm C), and conventional chemotherapy (Arm D). Patients choose their treatment arm with their physician.

How Is the Trial Designed?

Group I: Arm C - Adaptive Therapy Experimental Treatment 3 Interventions

Therapy with VAC that starts and stops based on response, adaptive timing of therapy, with a prolonged time to progression rather than complete remission goal

Group II: Arm B - Second Strike - Maintenance Experimental Treatment 5 Interventions

Participants will receive conventional doses of Vincristine/Actinomycin D/Cyclophosphamide (VAC) until complete response (CR) for 12-42 weeks and then switch to up to 2 years of vinorelbine/oral cyclophoshamide

Group III: Arm A - First Strike Experimental Treatment 3 Interventions

Participants will receive 42 weeks of conventional doses of vinorelbine, actinomycin D and cyclophosphamide

Group IV: Arm - D Conventional Therapy Active Control 3 Interventions

Participants will receive a chemotherapy combination based on published trials. An example would be 42 weeks of VAC but may also include irinotecan, doxorubicin, ifosfamide, etoposide.

Actinomycin D is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Dactinomycin for:

• Rhabdomyosarcoma
• Wilms tumor
• Ewing's sarcoma

Approved in United States as Actinomycin D for:

• Rhabdomyosarcoma
• Wilms tumor
• Ewing's sarcoma
• Trophoblastic neoplasm

Approved in Canada as Dactinomycin for:

• Rhabdomyosarcoma
• Wilms tumor
• Ewing's sarcoma

Who Is Running the Clinical Trial?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

National Pediatric Cancer Foundation

Collaborator

Trials

8

Recruited

300+

Published Research Related to This Trial

An 11-month-old boy with rhabdomyosarcoma resistant to standard chemotherapy (vincristine, actinomycin-D, cyclophosphamide, and adriamycin) achieved complete remission after receiving a new combination therapy of vinblastine, cis-platinum, and bleomycin (VPB therapy).

The VPB therapy not only effectively reduced the tumor size but also did so without causing severe adverse effects, indicating its potential as a safe and effective treatment option for resistant rhabdomyosarcoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Rhabdomyosarcoma of the urinary bladder: complete remission induced by vinblastine, cis-platinum, and bleomycin]. Tawa, A., Yabuta, R., Yuumura, K., et al.[2013]

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]

The pilot study involving 18 patients aged 2-23 years demonstrated that the combination of vinorelbine and low-dose cyclophosphamide is feasible and shows activity against recurrent sarcomas, with one complete remission and six partial remissions observed.

Vinorelbine at a dose of 25 mg/m2 resulted in manageable toxicity, with 37% of cycles showing Grade 3 or higher neutropenia, while the recommended maintenance doses for future trials are cyclophosphamide 25 mg/m2 daily and vinorelbine 25 mg/m2 on specific days.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vinorelbine and low-dose cyclophosphamide in the treatment of pediatric sarcomas: pilot study for the upcoming European Rhabdomyosarcoma Protocol. Casanova, M., Ferrari, A., Bisogno, G., et al.[2018]

Vinorelbine tartrate is an FDA-approved treatment for advanced, unresectable non-small cell lung cancer, known for its favorable safety profile and the ability to be administered weekly in an outpatient setting.

While approximately 40% of patients experience severe granulocytopenia, this side effect is quickly reversible, and only about 8% of patients need hospitalization for related complications, indicating that it can be managed effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vinorelbine tartrate: a promising new chemotherapeutic agent. Baldwin, PD.[2018]

The novel chemotherapy regimen, which includes vinorelbine with the VIVA combination, was feasible and led to a major response in all four patients with high-risk rhabdomyosarcoma after three cycles.

Despite significant hematological toxicity, there were no major complications or neurotoxicity, and all patients remained alive after a median follow-up of 11 months from diagnosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

VIVA (vinorelbine, ifosfamide, vincristine, actinomycin-D): A new regimen in the armamentarium of systemic therapy for high-risk rhabdomyosarcoma. Ferrari, A., Chiaravalli, S., Zecca, M., et al.[2021]

A meta-analysis of five Phase 2 trials involving 156 patients with relapsed or refractory rhabdomyosarcoma (RMS) showed that vinorelbine significantly increased response rates in patients with alveolar rhabdomyosarcoma (ARMS) by 41% compared to those with embryonal rhabdomyosarcoma (ERMS).

Vinorelbine demonstrated efficacy as a treatment option for relapsed RMS, particularly in ARMS patients, suggesting it warrants further investigation for newly diagnosed cases, as there was no significant difference in disease progression rates between ARMS and ERMS patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alveolar rhabdomyosarcoma has superior response rates to vinorelbine compared to embryonal rhabdomyosarcoma in patients with relapsed/refractory disease: A meta-analysis. Allen-Rhoades, W., Lupo, PJ., Scheurer, ME., et al.[2023]

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]

In a study of 24 pediatric patients with rhabdomyosarcoma, those treated with actinomycin-D had a higher 2-year overall survival rate (78.0%) compared to those treated with carboplatin (68.2%).

Despite the difference in survival rates, carboplatin was found to be a safe alternative to actinomycin-D, with no significant differences in hematological or non-hematological toxicities between the two treatment groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Replacing actinomycin-D with Carboplatin for newly diagnosed rhabdomyosarcoma. Sezgin, G., Acipayam, C., Bayram, I., et al.[2022]

Vinorelbine tartrate is an effective treatment for non-small cell lung cancer (NSCLC) and has a low reported prevalence of respiratory adverse effects, typically under 5%.

However, there is a potential risk of increased pulmonary toxicity in patients with diffuse pulmonary NSCLC, as demonstrated by a case of acute respiratory failure following vinorelbine infusion in a patient with a hypercoagulable state.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Respiratory failure following vinorelbine tartrate infusion in a patient with non-small cell lung cancer. Kouroukis, C., Hings, I.[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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2773476/

Vincristine, Actinomycin, and Cyclophosphamide Compared ... The purpose of this study was to compare the outcome of patients with intermediate-risk rhabdomyosarcoma (RMS) treated with standard VAC (vincristine, ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11824802/

Clinical outcomes of adult and childhood rhabdomyosarcoma ... Outcomes in adult patients with rhabdomyosarcoma are poor, with a 5-year survival rate of approximately 30 %. The current study aimed to compare the ...

3. journal.waocp.org journal.waocp.org/article_89560_f1b7b2ebd250adb4a4d54c7946a57672.pdf,https:/www.ncbi.nlm.nih.gov/pubmed/33906311,https:/pubmed.ncbi.nlm.nih.gov/33906311/,https:/www.ncbi.nlm.nih.gov/pmc/articles/PMC8325144,http:/journal.waocp.org/article_30918_04bce281fc135503057acd7cbceb92b7.pdf

Replacing Actinomycin-D with Carboplatin for Newly ... In conclusion, our data demonstrate the carboplatin can be used as an alternative to actinomycin-D chemotherapy in the treatment of rhabdomyosarcoma in ...

4. journals.lww.com journals.lww.com/md-journal/fulltext/2019/12270/phase_ii_study_of_vincristine,_actinomycin_d,.7.aspx

Phase II study of vincristine, actinomycin-D,... However, their results showed that the estimated 3-year failure-free survival (FFS) rate was 63% (95% CI: 46%, 75%), and the overall survival (OS) rate was 84% ...

5. ascopubs.org ascopubs.org/doi/10.1200/jco.2011.29.15_suppl.10092

Clinical outcomes in adult and childhood ... 10092 Background: The outcomes for the patients (pts) with adult RMS have remained poor, with approximately 30% at 5-year survival.

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2012/050682s029s030lbl.pdf

Cosmegen® for Injection (dactinomycin ... - accessdata.fda.gov This drug is HIGHLY TOXIC and both powder and solution must be handled and administered with care. Inhalation of dust or vapors and contact with skin or ...

7. dailymed.nlm.nih.gov dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=aa047ee8-f2e8-4720-84b1-d1c4532d6c63&type=display

highlights of prescribing information It has also been shown to be carcinogenic, mutagenic, embryotoxic and teratogenic. Due to the drug's toxic properties, appropriate precautions including the use ...

8. reference.medscape.com reference.medscape.com/drug/dactinomycin-342117

Dactinomycin dosing, indications, interactions, adverse ... Indicated for Wilms tumor as part of a multiphase, combination chemotherapy regimen. 45 mcg/kg IV every 3-6 weeks for up to 26 weeks.

9. mayoclinic.org mayoclinic.org/drugs-supplements/dactinomycin-intravenous-route/description/drg-20063277

Dactinomycin (intravenous route) - Side effects & uses Dactinomycin injection is used to treat certain types of cancer. This includes cancer of the bones and soft tissue, including muscles and tendons.

10. sciencedirect.com sciencedirect.com/topics/immunology-and-microbiology/dactinomycin

Dactinomycin - an overview Adverse effects of dactinomycin include myelosuppression, such as thrombocytopenia, leukopenia and anemia, nausea and vomiting, mucositis, stomatitis, diarrhea ...