Prexasertib + Irinotecan for Desmoplastic Small Round Cell Tumor and Rhabdomyosarcoma

Overseen By Emily Slotkin, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Memorial Sloan Kettering Cancer Center

Disqualifiers: Uncontrolled infection, Pregnant, Congestive heart failure, 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 tests a new combination of drugs for two rare cancers: desmoplastic small round cell tumor (DSRCT) and rhabdomyosarcoma (RMS). Researchers aim to determine if adding prexasertib, a potential new drug, to the standard drugs irinotecan and temozolomide is safe and effective. The goal is to identify the highest dose of prexasertib that results in only mild side effects. This trial may suit individuals whose DSRCT or RMS has not responded to standard therapies and who have measurable disease. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this potential new drug.

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

The trial protocol does not specify if you need to stop taking your current medications. However, you must have recovered from the effects of any prior cancer treatments, and certain time periods must have passed since your last cancer therapy.

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

Research shows that prexasertib, when combined with irinotecan, appears promising, but researchers are still carefully studying its safety. Earlier studies found that prexasertib, when used with similar drugs, was generally well-tolerated by patients, with most side effects being mild or manageable, such as nausea or fatigue.

Prexasertib remains in early testing, so researchers are gathering more information to confirm its safety. Since irinotecan is already used safely in other treatments, its risks are better understood. This study aims to determine the optimal dose of prexasertib that minimizes side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for DSRCT or RMS?

Researchers are excited about the combination of Prexasertib and Irinotecan for treating desmoplastic small round cell tumor and rhabdomyosarcoma because of its unique approach. Unlike traditional chemotherapy, which targets rapidly dividing cells in general, Prexasertib specifically inhibits a protein called CHK1, a key player in cell cycle control. This means it can potentially make cancer cells more vulnerable to DNA damage, especially when used alongside Irinotecan, which interferes with DNA replication. Together, they offer a novel strategy that could enhance treatment effectiveness and overcome resistance seen with conventional therapies.

What evidence suggests that this trial's treatments could be effective for DSRCT or RMS?

Research suggests that the combination of prexasertib and irinotecan, which participants in this trial will receive, may be promising for treating certain cancers, specifically desmoplastic small round cell tumor (DSRCT) and rhabdomyosarcoma (RMS). Prexasertib blocks certain proteins that cancer cells need to grow. Early studies have shown that this combination can lead to positive responses in patients with these cancers. Specifically, prexasertib demonstrated potential in shrinking DSRCT tumors in early tests. While more research is needed to confirm these findings, this combination is being carefully studied for its possible benefits. ^{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 ≥12 months with advanced or metastatic desmoplastic small round cell tumor or rhabdomyosarcoma that's resistant to standard treatments. They must have measurable disease, be in a certain health condition (Karnofsky/Lansky score), and have adequate organ function. Pregnant individuals, those with uncontrolled infections, heart conditions like congestive heart failure, or hypersensitivity to irinotecan are excluded.

Inclusion Criteria

absolute neutrophil count (ANC) ≥ 1500/mm^3

I have recovered from side effects of previous cancer treatments, except for hair loss.

My kidney function is normal or near normal.

Exclusion Criteria

Patients with known hypersensitivity to irinotecan or its excipients are not eligible

I do not have a history of heart issues like Torsades de Pointes, congestive heart failure, or family history of prolonged QT syndrome.

Patients for whom the investigator deems that irinotecan and temozolomide are not appropriate are not eligible

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating doses of Prexasertib in combination with Irinotecan and Temozolomide to determine the recommended phase II dose

1 year

Every 6-8 weeks for disease scans

Dose Expansion

Participants receive the recommended phase II dose of Prexasertib in combination with Irinotecan and Temozolomide to evaluate safety and efficacy

2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Irinotecan
• Prexasertib

Trial Overview The study tests the safety and effectiveness of prexasertib combined with standard drugs irinotecan and temozolomide in treating specific tumors. It aims to find the highest dose of prexasertib that participants can tolerate with few or mild side effects.

How Is the Trial Designed?

Group I: Prexasertib and Irinotecan Experimental Treatment 2 Interventions

Patients will have extent of disease scans following every 2 cycles (every 6 weeks on dose levels 0-3, and every 8 weeks on dose level -1 (if required). Patients will be allowed to continue therapy as long as they do not experience dose-limiting toxicities or progression of disease.

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?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04095221

NCT04095221 | A Study of the Drugs Prexasertib ... The purpose of this study is to test whether the study drug prexasertib is a safe and effective treatment for people with DSRCT or RMS when given in ...

2. asco.org asco.org/abstracts-presentations/ABSTRACT366976

A phase I/II study of prexasertib in combination with ... ... combined with data from other users or data about your activity on other sites. While the data collected on our site is aggregate or non-personal, the data ...

3. researchgate.net researchgate.net/publication/361125453_A_phase_III_study_of_prexasertib_in_combination_with_irinotecan_in_patients_with_relapsedrefractory_desmoplastic_small_round_cell_tumor_and_rhabdomyosarcoma

A phase I/II study of prexasertib in combination with ... A phase I/II study of prexasertib in combination with irinotecan in patients with relapsed/refractory desmoplastic small round cell tumor and rhabdomyosarcoma.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12052087/

ACR-368, a CHK1/2 Kinase Inhibitor, in Patients With ... We hypothesized that ACR-368 (prexasertib) would be active in desmoplastic small round cell tumor (DSRCT) because of favorable responses in ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40330140/

ACR-368, a CHK1/2 Kinase Inhibitor, in Patients With ... We hypothesized that ACR-368 (prexasertib) would be active in desmoplastic small round cell tumor (DSRCT) because of favorable responses in preclinical models.

6. aacrjournals.org aacrjournals.org/clincancerres/article/27/4/937/124807/The-Challenge-of-Combining-Chemo-and-Radiotherapy

The Challenge of Combining Chemo- and Radiotherapy with ... Preclinical models of cancer have demonstrated enhanced efficacy of cell-cycle checkpoint kinase inhibitors when used in combination with genotoxic agents.