Irinotecan + Carboplatin for Rhabdomyosarcoma

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Disqualifiers: Prior chemotherapy, Prior radiotherapy, Pregnancy, 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: Approximately 36 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of a combination of two chemotherapy drugs, irinotecan and carboplatin, in treating rhabdomyosarcoma (a type of cancer that forms in soft tissue) when used as the initial treatment. The goal is to determine if these drugs can effectively stop tumor cells from growing or cause them to die. The trial seeks participants recently diagnosed with intermediate- or high-risk rhabdomyosarcoma who have not yet received treatment. Those with this diagnosis who haven't started other cancer treatments might be a good fit for the study. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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 patients generally tolerate the combination of irinotecan and carboplatin well. In earlier studies, the most common serious side effects included a low white blood cell count in 46% of patients and stomach pain in 17% of patients. These findings suggest that while some side effects can be serious, they do not affect everyone. Another study found that some patients experienced skin issues, such as rashes, but these were less common. Overall, this combination treatment has demonstrated a manageable safety profile for many patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using Irinotecan and Carboplatin for rhabdomyosarcoma because these drugs offer a fresh approach compared to the standard treatments like vincristine, dactinomycin, and cyclophosphamide. Irinotecan works by targeting DNA replication in cancer cells, which may enhance the effectiveness of chemotherapy. Meanwhile, Carboplatin is known for causing fewer side effects than other platinum-based drugs, potentially making the treatment more tolerable for patients. This combination could offer a new hope for those with intermediate- and high-risk rhabdomyosarcoma by improving outcomes with a different mechanism of action and reduced toxicity.

What evidence suggests that this treatment might be an effective treatment for rhabdomyosarcoma?

Research has shown that using irinotecan and carboplatin together can help treat rhabdomyosarcoma, a type of cancer. One study found that 89% of patients had their cancer controlled for 2.5 years, meaning the tumors did not grow back or spread during that time. Although serious side effects like low white blood cell counts and stomach pain can occur, most people handle the treatment well. Early results also indicate that combining this treatment with radiation therapy is effective and generally well-tolerated. These findings suggest that this treatment combination may effectively stop tumor growth in patients with intermediate- and high-risk rhabdomyosarcoma, which is the focus of this trial. ^{1 2 6 7 8}

Who Is on the Research Team?

Leonard Wexler, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT00077285

Irinotecan and Carboplatin as Upfront Window Therapy in ... PURPOSE: This phase II trial is studying how well giving irinotecan together with carboplatin as upfront window therapy (first-line therapy) works in treating ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/22619050/

Concurrent radiation with irinotecan and carboplatin in ... With median follow-up of 32 months, 2.5 year actuarial local control was 89%. Among all patients, grades 3 and 4 dermatitis were observed in 11% ...

3. ascopubs.org ascopubs.org/doi/10.1200/jco.2010.28.15_suppl.9533

Phase II window of irinotecan plus carboplatin in newly ... Background: There has been little improvement in outcome for patients (pts) with intermediate (INT)- and high-risk (HR) rhabdomyosarcoma (RMS) ...

4. withpower.com withpower.com/trial/irinotecan-carboplatin-for-rhabdomyosarcoma-8a95a

Irinotecan + Carboplatin for Rhabdomyosarcoma Irinotecan was generally well-tolerated, with the most common severe side effects being neutropenia (46%) and abdominal pain (17%), indicating that while the ...

5. redjournal.org redjournal.org/article/S0360-3016(10)01062-X/fulltext

Feasibility and Efficacy of Radiation Therapy (RT) with ... Preliminary results of I+C with concurrent RT in intermediate and high-risk RMS demonstrate favorable tolerability and local control.

6. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/abs/10.1002/pbc.24205

Concurrent radiation with irinotecan and carboplatin in ... With median follow-up of 32 months, 2.5 year actuarial local control was 89%. Among all patients, grades 3 and 4 dermatitis were observed in 11% ...

7. trial.medpath.com trial.medpath.com/clinical-trial/fc9815174a4df8bf/nct00077285-pilot-trial-irinotecan-carboplatin-rhabdomyosarcoma

Irinotecan and Carboplatin as Upfront Window Therapy in ... 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 ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT00077285?tab=history&a=39

Record History | ver. 39: 2014-09-16 | NCT00077285 Determine the safety and feasibility of administering maintenance therapy comprising irinotecan to patients with high-risk rhabdomyosarcoma treated with this ...