BAY 1895344 + FOLFIRI for Stomach and Intestinal Cancer

Not currently recruiting at 13 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A4 substrates

Disqualifiers: ATR inhibitor, Uncontrolled illness, Psychiatric, others

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

Compensation: Varies

Number of Visits: 4

Duration: 28 days per cycle

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effects of a new treatment combination for individuals with advanced or metastatic stomach and intestinal cancers. It combines a new drug, BAY 1895344, which may halt tumor growth by blocking certain cell growth enzymes, with a chemotherapy regimen called FOLFIRI. FOLFIRI, which includes Fluorouracil, Irinotecan Hydrochloride, and Leucovorin Calcium, works by stopping cancer cells from growing and spreading. The trial aims to determine the best dose and understand the potential benefits and side effects of this combination. It seeks participants who have progressed on at least one prior treatment for metastatic stomach or intestinal cancer and for whom FOLFIRI is considered a reasonable treatment option. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

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

The trial does not specify if you must stop taking your current medications, but you cannot take medications that strongly interact with CYP3A4 enzymes. It's best to discuss your current medications with the trial team to ensure they don't interfere with the study drugs.

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

Previous studies found that BAY 1895344, also known as elimusertib, was generally well tolerated by patients and showed activity against certain cancers, particularly those with specific DNA repair issues. FOLFIRI, a chemotherapy mix of irinotecan, leucovorin, and 5-fluorouracil, has been effective for digestive cancers and is generally well tolerated, though it can have side effects. Research suggests that combining BAY 1895344 with FOLFIRI could be safe, but this combination is still undergoing initial testing in humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the treatment with BAY 1895344 in combination with FOLFIRI for stomach and intestinal cancer because it offers a novel approach to targeting cancer cells. Unlike the standard treatments, which typically focus on stopping cancer cell growth through chemotherapy, BAY 1895344, also known as elimusertib, is an ATR inhibitor. This means it specifically targets the ATR protein, which is crucial for cancer cells to repair their DNA and survive. By disrupting this repair process, elimusertib may enhance the effectiveness of traditional chemotherapy, potentially improving treatment outcomes for patients.

What evidence suggests that BAY 1895344 in combination with FOLFIRI might be an effective treatment for advanced or metastatic stomach and intestinal cancer?

Research has shown that BAY 1895344, which participants in this trial may receive, has yielded promising results in early studies, particularly in cases where cancer cells struggle to repair DNA damage. This treatment blocks certain proteins that cancer cells need for growth. Early findings suggest that when combined with FOLFIRI, another treatment option in this trial, BAY 1895344 may help reduce stomach and intestinal cancers that have spread.

FOLFIRI, a mix of chemotherapy drugs, has proven effective for treating digestive cancers. Studies indicate it can increase the chances of a positive response and help prevent cancer growth. Together, these treatments may target cancer cells more effectively. ^{1 2 3 6 7}

Who Is on the Research Team?

Liza C. Villaruz

Principal Investigator

University of Pittsburgh Cancer Institute LAO

Are You a Good Fit for This Trial?

Adults with advanced or metastatic stomach/intestinal cancer who've progressed after first-line therapy can join. They must have adequate organ function, no severe reactions to similar drugs, and agree to use contraception. Those with certain viral infections must be stable on treatment without interactions.

Inclusion Criteria

Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x institutional ULN

Platelets >= 100,000/mcL

I am fully active or can carry out light work.

Exclusion Criteria

I have had cancer before, but it won't interfere with this study.

Patients with psychiatric illness/social situations that would limit compliance with study requirements

I have a stomach or intestine condition that affects how I absorb pills.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive elimusertib orally and FOLFIRI intravenously in 28-day cycles

28 days per cycle

Multiple visits per cycle for drug administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 1 year

Every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• BAY 1895344
• Fluorouracil
• Irinotecan Hydrochloride
• Leucovorin Calcium

Trial Overview The trial is testing BAY 1895344 combined with FOLFIRI chemotherapy against cancers of the stomach and intestines. It aims to find the best dose and assess benefits/side effects by seeing if this combination can shrink tumors more effectively than standard treatments.

How Is the Trial Designed?

Group I: Treatment (elimusertib, FOLFIRI) Experimental Treatment 7 Interventions

Patients receive elimusertib PO QD on days 2, 3, 16, and 17 and irinotecan hydrochloride IV over 90 minutes, fluorouracil IV over 46 hours, and leucovorin calcium IV on days 1 and 15. Cycles repeat every 28 day in the absence of disease progression or unacceptable toxicity. Patients undergo tumor biopsy during screening and on study and blood sample collection and imaging throughout the study.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Citations

1. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT04535401/

Clinical Trial: NCT04535401 Giving BAY 1895344 in combination with FOLFIRI may help shrink advanced or metastatic stomach and/or intestinal cancer.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10082586/

PMC Search Update - PubMed Central - NIH Clinical PK data of single agent BAY-1895344 found dose proportional exposure and no evidence of saturable absorption among the entire investigated dose ...

3. aacrjournals.org aacrjournals.org/mct/article/19/1/26/92777/The-Novel-ATR-Inhibitor-BAY-1895344-Is-Efficacious

The Novel ATR Inhibitor BAY 1895344 Is Efficacious as ... BAY 1895344 exhibited strong monotherapy efficacy in cancer xenograft models that carry DNA damage repair deficiencies. The combination of BAY 1895344 with DNA ...

4. centerwatch.com centerwatch.com/clinical-trials/listings/NCT04535401/testing-the-addition-of-an-anticancer-drug-bay-1895344-to-the-usual-chemotherapy-with-folfiri-in-advanced-or-metastatic-cancers-of-the-stomach-and-intestines

Testing the Addition of an Anticancer Drug, BAY 1895344, ... Giving BAY 1895344 in combination with FOLFIRI may help shrink advanced or metastatic stomach and/or intestinal cancer. Read more ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9797429/

Elimusertib (BAY1895344), a Novel ATR Inhibitor ... Elimusertib (BAY1895344), a novel ATR inhibitor, demonstrates in vivo activity in ATRX mutated models of uterine leiomyosarcoma.

6. aacrjournals.org aacrjournals.org/cancerdiscovery/article/11/1/80/3075/First-in-Human-Trial-of-the-Oral-Ataxia

First-in-Human Trial of the Oral Ataxia Telangiectasia and ... Overall, BAY 1895344 is well tolerated, with antitumor activity against cancers with certain DDR defects, including ATM loss. An expansion phase continues in ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04616534

NCT04616534 | Testing the Addition of an Anti-cancer ... This phase I trial identifies the best dose, possible benefits and/or side effects of gemcitabine in combination with elimusertib (BAY 1895344)