Irinotecan + Temozolomide for Ewing Sarcoma

Not currently recruiting at 8 trial locations

Overseen By Emily Slotkin, MD

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Disqualifiers: Prior chemotherapy, Prior radiotherapy, Pregnant, Breastfeeding, 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 12-18 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how the chemotherapy drugs irinotecan and temozolomide perform alongside standard treatments for Ewing sarcoma, a type of cancer. Researchers aim to determine if adding these drugs can improve treatment outcomes. Participants must have newly diagnosed Ewing sarcoma and must not have received prior treatment for it. The trial is open to those who meet these criteria and are interested in exploring a potentially more effective treatment approach. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people, offering participants a chance to contribute to potentially groundbreaking advancements in Ewing sarcoma treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, since prior chemotherapy or radiotherapy is not allowed, you may need to discuss your current treatments with the trial team.

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

Research has shown that combining the drugs irinotecan and temozolomide is effective and safe for patients with relapsed Ewing sarcoma, a type of cancer. Studies found that patients generally tolerated these drugs well when used together. No major safety issues were reported, and many patients experienced positive outcomes, such as tumor reduction or disease stabilization.

These findings suggest that the treatment is generally safe and effective, particularly for patients with recurrent cancer. However, this combination has not yet been tested in newly diagnosed Ewing sarcoma patients, so its effects in this group remain under investigation. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining irinotecan and temozolomide for Ewing sarcoma because it offers a new approach to treatment. Unlike the standard chemotherapy agents like doxorubicin, cyclophosphamide, and ifosfamide, which are commonly used, this combination targets cancer cells in a unique way. Irinotecan is a topoisomerase inhibitor, which prevents cancer cells from properly dividing, while temozolomide is an oral alkylating agent that damages the DNA of cancer cells, leading to their death. This dual-action approach could enhance effectiveness and potentially improve outcomes for both localized and metastatic Ewing sarcoma patients.

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

Research has shown that the combination of irinotecan and temozolomide holds potential for treating relapsed Ewing sarcoma. In earlier studies, this treatment shrank tumors in more than half of the patients. On average, patients experienced a period of 3.8 to 8.3 months before the disease worsened, and about 44% did not see their disease progress for at least a year. These results suggest that irinotecan and temozolomide can help control the disease for a time in patients with relapsed Ewing sarcoma. In this trial, patients with localized disease will receive this combination as part of their maintenance therapy, while those with metastatic disease will receive it intercalated with standard chemotherapy. Although this treatment is also being tested for newly diagnosed cases, its success in relapsed cases offers hope. ^{1 2 3 4 6}

Who Is on the Research Team?

Emily Slotkin, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients aged 1 to 40 years with newly diagnosed, untreated Ewing sarcoma. They must have normal heart and kidney function, adequate liver function even if the tumor involves the liver, and sufficient blood cell counts. Participants need a central venous catheter and must agree to use contraception if of reproductive potential.

Inclusion Criteria

I was diagnosed with my condition between the ages of 1 and 40.

I have been newly diagnosed with Ewing sarcoma and have not received any treatment.

My kidney function tests are normal.

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 a combination of irinotecan and temozolomide with the standard EFT regimen

Approximately 12-18 months

Multiple cycles with frequent visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 years

Long-term follow-up

Monitoring of event-free survival and adverse events

4 years

What Are the Treatments Tested in This Trial?

Interventions

• Irinotecan
• Temozolomide

Trial Overview The study tests adding irinotecan and temozolomide (chemotherapy drugs) to the existing high-dose alkylator-based chemotherapy regimen (EFT), along with surgery/radiation as needed. This combination aims to improve outcomes in patients who are newly diagnosed with Ewing sarcoma.

How Is the Trial Designed?

Group I: Patients with metastatic disease Experimental Treatment 12 Interventions

Patients will get 10 cycles of the combination intercalated between the final 4 cycles of standard chemotherapy. * Cycles 4, 5, 7, 8, 10, 11, 13, 14, 16, and 17 will include: * Irinotecan will be given on 10 days over weeks 1 and 2 of a cycle at a dose of 20 mg/m2/day intravenously * Temozolomide will be given daily on the first 5 days of irinotecan administration at a dose of 100 mg/m2/day orally or intravenously * Cycles 6, 9, and 12 will include: * Ifosfamide 2,800 mg/m2/day on days 1-5 * Etoposide 100 mg/m2/day on days 1-5 * Cycle 15 will include: * Cyclophosphamide will be given on days 1 and 2 at a dose of 2,100 mg/m2/day, or for patients \< 10 years of age at a dose of 70 mg/kg/day * Doxorubicin will be given on days 1 and 2 at a dose of 37.5 mg/m2/day * Vincristine will be given on day 1 at a dose of 2 mg/m2 or 0.067 mg/kg (whichever is lower, to a max dose of 2 mg)

Group II: Patients with localized disease Experimental Treatment 12 Interventions

Patients with localized disease will receive six cycles of the combination as "maintenance" therapy following standard chemotherapy. * Cycles 4-6 will include: * Ifosfamide 2,800 mg/m2/day on days 1-5 * Etoposide 100 mg/m2/day on days 1-5 * Cycle 7 will include : * Cyclophosphamide will be given on days 1 and 2 at a dose of 2,100 mg/m2/day, or for patients \< 10 years of age at a dose of 70 mg/kg/day * Doxorubicin will be given on days 1 and 2 at a dose of 37.5 mg/m2/day * Vincristine will be given on day 1 at a dose of 2 mg/m2 or 0.067 mg/kg (whichever is lower, to a max dose of 2 mg) * Cycles 8-13 will include: * Irinotecan will be given on 10 days over weeks 1 and 2 of a cycle at a dose of 20 mg/m2/day intravenously * Temozolomide will be given daily on the first 5 days of irinotecan administration at a dose of 100 mg/m2/day orally or intravenously

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Published Research Related to This Trial

In a study of 51 patients with recurrent Ewing sarcoma, the combination of temozolomide and irinotecan (TEMIRI) demonstrated a disease control rate of 71%, indicating significant efficacy in managing this cancer.

Factors such as the Eastern Cooperative Oncology Group (ECOG) performance status and lactate dehydrogenase (LDH) levels were found to significantly influence progression-free survival, highlighting their potential as predictive markers for treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irinotecan and temozolomide in recurrent Ewing sarcoma: an analysis in 51 adult and pediatric patients. Palmerini, E., Jones, RL., Setola, E., et al.[2018]

Irinotecan and temozolomide (IT) chemotherapy is effective for treating relapsed Ewing sarcoma, showing similar objective response rates (28% in both pediatric and adult patients) and manageable toxicity levels across age groups.

However, pediatric patients experienced significantly longer progression-free survival (7.4 months) compared to adults (2.2 months), suggesting that age may influence treatment outcomes and warrant further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irinotecan and temozolomide chemotherapy in paediatric and adult populations with relapsed Ewing Sarcoma. Salah, S., To, YH., Khozouz, O., et al.[2021]

The protracted d × 5×2 schedule of vincristine, irinotecan, and temozolomide (VIT) demonstrated a significantly higher objective response rate (54.5%) compared to the shorter d × 5 schedule (20.8%) in patients with relapsed or refractory Ewing sarcoma, based on a study of 46 patients.

Patients on the d × 5 schedule experienced more severe adverse events, indicating that the d × 5×2 schedule not only provided better efficacy but also had a more favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Longer versus Shorter Schedules of Vincristine, Irinotecan, and Temozolomide (VIT) for Relapsed or Refractory Ewing Sarcoma: A Randomized Controlled Phase 2 Trial. Xu, J., Xie, L., Sun, X., et al.[2023]

A combination of temozolomide and irinotecan was found to be tolerable and active in treating advanced Ewing sarcoma, with 1 complete response and 3 partial responses observed among 14 evaluable patients.

The treatment regimen was manageable, with minimal myelosuppression and only 11% of courses experiencing grade 3-4 diarrhea, suggesting that home administration of irinotecan is safe and feasible for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide and intravenous irinotecan for treatment of advanced Ewing sarcoma. Wagner, LM., McAllister, N., Goldsby, RE., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8969362/

Irinotecan plus temozolomide in relapsed Ewing sarcoma Irinotecan plus temozolomide combination chemotherapy showed antitumor activity and an acceptable safety profile in patients with relapsed Ewing sarcoma.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT01864109

Irinotecan and Temozolomide in Combination With Existing ... The purpose of this study is to find out what effects, good and/or bad, the combination of irinotecan and temozolomide has on Ewing sarcoma.

3. cancertherapyadvisor.com cancertherapyadvisor.com/news/ewing-sarcoma-irinotecan-temozolomide-effective-safe-treatment-risk/

Irinotecan-Temozolomide "Effective and Safe" for Relapsed ... The median progression-free survival (PFS) ranged from 3.8 months to 8.3 months, and the 1-year PFS rate was 44.4%. The median overall survival ...

4. clinicaltrial.be clinicaltrial.be/en/details/75168?per_page=20&only_recruiting=0&only_eligible=0&only_active=0

Irinotecan and Temozolomide in Combination With Existing... The purpose of this study is to find out what effects, good and/or bad, the combination of irinotecan and temozolomide has on Ewing sarcoma.

5. aacrjournals.org aacrjournals.org/clincancerres/article/29/9/1689/725869/Pilot-Study-of-Recurrent-Ewing-s-Sarcoma

Pilot Study of Recurrent Ewing's Sarcoma Management with ... The combination of irinotecan (IRI) and temozolomide (TEM), in relapsed patients with ES has demonstrated an objective response rate (ORR) of 55% and median PFS ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/19637327/

Irinotecan and temozolomide for Ewing sarcoma Conclusions: Irinotecan and temozolomide is a well-tolerated and active regimen for recurrent/progressive ES. Prospective trials are necessary to define the ...