Irinotecan + Carboplatin for Rhabdomyosarcoma

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

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: Approximately 36 weeks

65 Participants Needed

Trial Summary

What is the purpose of this trial?

RATIONALE: Drugs used in chemotherapy, such as irinotecan and carboplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Giving more than one drug may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving irinotecan together with carboplatin as upfront window therapy (first-line therapy) works in treating patients with newly diagnosed intermediate-risk or high-risk rhabdomyosarcoma.

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 combination of Irinotecan and Carboplatin for treating rhabdomyosarcoma?

Research shows that Irinotecan is highly active against rhabdomyosarcoma, and preclinical testing suggests that combining it with Carboplatin has at least additive antitumor activity. Additionally, studies have explored the use of these drugs in combination with radiation therapy, indicating potential effectiveness in treating this cancer. ^{1 2 3 4 5}

Is the combination of Irinotecan and Carboplatin safe for humans?

The combination of Irinotecan and Carboplatin has been studied for safety in children with various cancers, including rhabdomyosarcoma. Some studies report that high doses of Carboplatin can cause kidney problems, but the combination is generally considered safe at recommended doses, with careful monitoring for side effects. ^{1 2 3 6 7}

How is the drug combination of Irinotecan and Carboplatin unique for treating rhabdomyosarcoma?

The combination of Irinotecan and Carboplatin is unique for treating rhabdomyosarcoma because it is used alongside radiation therapy to enhance its effectiveness, and Irinotecan is known for its strong activity against this type of cancer. This approach is being studied for its potential to improve local control of the tumor while managing side effects. ^{1 2 3 5 8}

Research Team

Leonard Wexler, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for patients under 50 years old with newly diagnosed, untreated rhabdomyosarcoma or related sarcomas. They must have normal organ function, no prior chemotherapy or radiotherapy, and be willing to use contraception if of childbearing potential. It's aimed at those with intermediate-risk or high-risk features as specified in the study criteria.

Inclusion Criteria

Consent to an indwelling central venous catheter

My kidney, liver, heart, and blood tests are normal.

My cancer is at an advanced stage or is a high-risk type.

Exclusion Criteria

Pregnant or breastfeeding females

I have not had chemotherapy or radiotherapy, except for emergency treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive irinotecan and carboplatin as upfront window therapy, followed by vincristine, dexrazoxane, doxorubicin, cyclophosphamide, and G-CSF over multiple courses

Approximately 36 weeks

Radiotherapy

Participants undergo radiotherapy once daily, 5 days a week, for 4-5.5 weeks after course 5

4-5.5 weeks

Maintenance Therapy

High-risk patients receive irinotecan maintenance therapy over 6 courses

18 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Long-term (monthly for 1 year, every 3 months for 1 year, every 6 months for 1 year, then annually)

Treatment Details

Interventions

• Carboplatin
• Irinotecan Hydrochloride

Trial Overview The trial is testing a combination of chemotherapy drugs irinotecan and carboplatin as first-line treatment for rhabdomyosarcoma. The goal is to see how well these drugs work together in stopping tumor growth by preventing cancer cells from dividing.

Participant Groups

Group I: pts with intermediate- and high-risk rhabdomyosarcoma Experimental Treatment 11 Interventions

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

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a study of 60 patients with newly diagnosed intermediate- or high-risk rhabdomyosarcoma, the combination of irinotecan and carboplatin with radiotherapy showed a high local control rate of 89% over a median follow-up of 32 months.

The treatment was well-tolerated, with lower rates of severe mucositis compared to historical data, indicating that this combination may be a safe and effective option for managing RMS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent radiation with irinotecan and carboplatin in intermediate- and high-risk rhabdomyosarcoma: a report on toxicity and efficacy from a prospective pilot phase II study. Dharmarajan, KV., Wexler, LH., Wolden, SL.[2018]

In a study involving 69 pediatric patients with newly diagnosed metastatic rhabdomyosarcoma, the combination of vincristine and irinotecan showed a high response rate of 70% for partial or complete responses, significantly outperforming irinotecan alone, which had a response rate of 42%.

The combination therapy demonstrated a low progressive disease rate of only 8%, and while irinotecan was associated with gastrointestinal toxicities, the differing mechanisms of action and toxicity profiles suggest that this combination could be a promising treatment option for further research in intermediate-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two consecutive phase II window trials of irinotecan alone or in combination with vincristine for the treatment of metastatic rhabdomyosarcoma: the Children's Oncology Group. Pappo, AS., Lyden, E., Breitfeld, P., et al.[2018]

In a phase II study involving 35 pediatric patients with recurrent or refractory rhabdomyosarcoma, irinotecan showed an overall response rate of 11.4%, with 2.9% achieving complete responses and 8.5% partial responses.

Irinotecan was generally well-tolerated, with the most common severe side effects being neutropenia (46%) and abdominal pain (17%), indicating that while the treatment had limited efficacy, it was manageable in terms of safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of irinotecan in children with relapsed or refractory rhabdomyosarcoma: a joint study of the French Society of Pediatric Oncology and the United Kingdom Children's Cancer Study Group. Vassal, G., Couanet, D., Stockdale, E., et al.[2018]

References

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

Concurrent radiation with irinotecan and carboplatin in intermediate- and high-risk rhabdomyosarcoma: a report on toxicity and efficacy from a prospective pilot phase II study. [2018]

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

Phase 1 and pharmacokinetic study of concurrent carboplatin and irinotecan in subjects aged 1 to 21 years with refractory solid tumors. [2018]

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

Two consecutive phase II window trials of irinotecan alone or in combination with vincristine for the treatment of metastatic rhabdomyosarcoma: the Children's Oncology Group. [2018]

4. England pubmed.ncbi.nlm.nih.gov

Response of previously untreated metastatic rhabdomyosarcoma to combination chemotherapy with carboplatin, epirubicin and vincristine. [2019]

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

Topotecan/carboplatin regimen for refractory/recurrent rhabdomyosarcoma in children: Report from the AIEOP Soft Tissue Sarcoma Committee. [2022]

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

Acute renal failure in high dose carboplatin chemotherapy. [2019]

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

Phase II trial of irinotecan in children with relapsed or refractory rhabdomyosarcoma: a joint study of the French Society of Pediatric Oncology and the United Kingdom Children's Cancer Study Group. [2018]

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

Irinotecan for children with relapsed solid tumors. [2018]