Trabectedin + Irinotecan for Ewing Sarcoma

(U01CA236220 Trial)

No longer recruiting at 5 trial locations

Overseen By SARC

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Sarcoma Alliance for Research through Collaboration

Must not be taking: Trabectedin, Lurbinectedin, Irinotecan, Topotecan

Disqualifiers: Brain metastases, Bleeding diathesis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 6

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a combination of two drugs, trabectedin and irinotecan (also known as Camptosar or CPT-11), to treat Ewing sarcoma, a rare and aggressive cancer. The study aims to determine the effectiveness of these drugs, particularly in patients with a specific mutation called EWS-FLI1. Participants will undergo special PET scans to help researchers assess the treatment's progress. The trial seeks individuals with Ewing sarcoma that has returned or not responded to other treatments and who have a measurable tumor. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking research.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but you cannot be on other investigational drugs or anticancer agents. It's best to discuss your current medications with the trial team.

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

Research has shown that combining trabectedin and irinotecan yields promising results in treating Ewing sarcoma, a type of cancer. In one study involving patients who had already received multiple treatments, this combination helped shrink tumors in 5 out of 16 patients.

Earlier studies suggest that this treatment is generally safe, though side effects can occur, as with any cancer treatment. Participants should discuss potential risks and benefits with their doctors. The current phase of the trial aims to further assess the safety and effectiveness of this treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments for Ewing sarcoma?

Researchers are excited about the combination of Trabectedin and Irinotecan for Ewing Sarcoma because this treatment approach uses a unique mechanism to target cancer cells. Unlike conventional options like chemotherapy with drugs such as Vincristine, Doxorubicin, and Cyclophosphamide, Trabectedin works by binding to the DNA of cancer cells, disrupting their replication process. This mechanism is different from most treatments that focus on stopping cell division. Additionally, the use of imaging scans in this treatment protocol allows doctors to better monitor how the cancer responds at an early stage, potentially leading to more tailored and effective treatments for patients.

What evidence suggests that trabectedin and irinotecan could be effective for Ewing sarcoma?

This trial will evaluate the combination of trabectedin and irinotecan for treating Ewing sarcoma, a rare cancer. Research has shown that using trabectedin and irinotecan together may help treat Ewing sarcoma. One study found that this combination was effective in patients who had already received extensive treatment, with several patients experiencing tumor shrinkage. Early research also suggests that these drugs work well together, boosting each other's effects on Ewing sarcoma cells. Trabectedin blocks a protein that aids cancer growth, while irinotecan attacks the cancer cells directly. This combination has stabilized the disease and reduced tumor activity. ^{1 6 7 8 9}

Who Is on the Research Team?

Patrick Grohar, MD

Principal Investigator

Children's Hospital of Philadelphia

John Glod, MD/PhD

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

This trial is for patients with relapsed and refractory Ewing sarcoma, specifically the EWS-FLI1 fusion type. Participants must have measurable disease, be in a relatively stable condition (ECOG 0-2 or Lansky ≥50), and agree to undergo tumor biopsies. They should not be pregnant or breastfeeding, have no known therapy that prolongs survival, and must not have used certain drugs like trabectedin.

Inclusion Criteria

Written, voluntary consent

I am willing to have a tumor biopsy.

My organs are working well.

Exclusion Criteria

You have had an allergic reaction in the past to irinotecan or topotecan or any substances they contain.

Pregnant or breastfeeding

Unable to comply with the safety monitoring requirements

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase I Treatment

Trabectedin administered as a 1-hour infusion followed by irinotecan infusions on day 2 and day 4 of 21-day cycles

Completed on 11/16/2022

3 visits per cycle (in-person)

Phase II Treatment

Trabectedin and irinotecan combination treatment with 18F-FLT PET imaging to evaluate treatment effect

Ongoing

3 visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 36 months

What Are the Treatments Tested in This Trial?

Interventions

• Irinotecan
• Trabectedin

Trial Overview The study tests trabectedin combined with irinotecan for treating Ewing sarcoma. It includes an infusion of a diagnostic agent (18F-FLT) followed by PET scans to assess treatment effects. The first phase has been completed; the second phase is now recruiting participants to further evaluate safety and efficacy.

How Is the Trial Designed?

Group I: Trabectedin and Irinotecan Experimental Treatment 4 Interventions

Trabectedin will be delivered by infusion on day 1 followed by 2 doses on irinotecan delivered by infusion for one hour on day 2 and day 4 of 21 day cycles. Some patients will receive an 18F-FLT Imaging scan prior to the first administration of trabectedin and once after administration of trabectedin.

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

Approved in United States as Camptosar for:

• Colorectal cancer

Approved in European Union as Irinotecan for:

• Colorectal cancer

Approved in Japan as Topotecin for:

• Colorectal cancer
• Small cell lung cancer

Approved in Canada as Irinotecan for:

• Colorectal cancer

Who Is Running the Clinical Trial?

Sarcoma Alliance for Research through Collaboration

Lead Sponsor

Trials

26

Recruited

2,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Janssen Scientific Affairs, LLC

Industry Sponsor

Trials

165

Recruited

579,000+

Joaquin Duato

Janssen Scientific Affairs, LLC

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen Scientific Affairs, LLC

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.11508

SARC037: Phase II results of trabectedin given as a 1-hour ... Conclusions: T+I exhibited anti-tumor activity in heavily pretreated pts with ES and met its prespecified ORR with 5 PRs in 16 evaluable ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5098094/

Trabectedin Followed by Irinotecan Can Stabilize Disease ... Preclinical data indicate that trabectedin followed by irinotecan has strong synergistic effects on Ewing sarcoma. This is presumably due to ...

3. aacrjournals.org aacrjournals.org/clincancerres/article/21/6/1373/128472/Trabectedin-Efficacy-in-Ewing-Sarcoma-Is-Greatly

Trabectedin Efficacy in Ewing Sarcoma Is Greatly Increased ... Results: We confirm that both trabectedin and doxorubicin were able to strongly reduce EWS–FLI1 (both type I and type II) binding to two representative target ...

4. journals.biologists.com journals.biologists.com/dmm/article/16/6/dmm049649/316733/Effectiveness-of-irinotecan-plus-trabectedin-on-a

Effectiveness of irinotecan plus trabectedin on a ... Vinorelbine, irinotecan and eribulin achieved nearly complete tumor growth inhibition (max TVI, 96-98%), although tumors regrew after the end of treatment. The ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2950329924001280

Trabectedin promotes oncolytic virus antitumor efficacy, ... Trabectedin reduced enrichment of the virus-induced intracellular antiviral response in human Ewing sarcoma cells (Figure 2G). This decrease in ...

6. sarctrials.org sarctrials.org/clinical-trials/sarc037/

SARC037 Ewing Sarcoma Trial: Now recruiting for patients A Phase I/II Study to Evaluate the Safety of Trabectedin Administered as a 1-Hour infusion in Ewing Sarcoma Patients in Combination with Low Dose Irinotecan.

7. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT04067115/

Clinical Trial: NCT04067115 - Ewing Sarcoma This study evaluates the trabectedin and irinotecan in the treatment of Ewings sarcoma, with a EWS-FLI1 mutation. Patients will also receive ...

8. trial.medpath.com trial.medpath.com/clinical-trial/5b54dd263536592d/nct04067115-safety-trabectedin-ewing-sarcoma

A Phase I/II Study to Evaluate the Safety of Trabectedin in ... Trabectedin and Irinotecan may inhibit the activity of this Ewing sarcoma mutation. Trabectedin may suppress the proliferation of the gene involved in DNA ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11155282/

Emerging therapies in Ewing sarcoma - PMC Patients with recurrent or refractory disease have poor outcomes with a median overall survival of around 12 months [8]. Multiple regimens are ...