Elimusertib + Chemotherapy for Pancreatic and Ovarian Cancer

Not currently recruiting at 2 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A4 substrates

Disqualifiers: Untreated brain metastases, Cardiac disease, others

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

Compensation: Varies

Number of Visits: 5

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial studies a combination treatment for advanced pancreatic and ovarian cancers that have spread. It aims to determine the best dose and observe any benefits or side effects of using gemcitabine, a chemotherapy drug, with elimusertib (also known as BAY 1895344, an experimental treatment), which may help stop cancer cells from growing. The trial seeks participants who have tried at least one treatment for their cancer, have a measurable tumor, and for whom standard treatments are no longer an 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 treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot receive chemotherapy, targeted therapy, or immunotherapy within 3 weeks of starting the trial, and you cannot take certain medications that interact with the trial drugs. It's best to discuss your current medications with the trial team to ensure they don't interfere with the study.

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

Research shows that elimusertib, when used alone, might help treat certain cancers, such as small cell lung cancer and gastrointestinal cancer. However, detailed safety information about elimusertib is still being collected. Since early studies are testing it, its safety is not yet fully understood.

In contrast, gemcitabine has been used for a longer time and is approved for certain cancers. Past studies found that about 10% of patients stopped using gemcitabine due to side effects. This indicates that while most people tolerate it well, some experience significant side effects.

These studies suggest that while gemcitabine is generally considered safe, elimusertib's safety in humans is still being explored. This trial aims to better understand how these two treatments work together and assess their safety for people. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the treatment involving elimusertib combined with gemcitabine for pancreatic and ovarian cancers because it represents a novel approach. Elimusertib is an ATR inhibitor, which targets the DNA damage response pathway, potentially enhancing the effectiveness of chemotherapy drugs like gemcitabine. This mechanism is different from most standard treatments, which typically focus on directly attacking cancer cells, as elimusertib aims to make cancer cells more susceptible to destruction. By combining these therapies, there is hope for improved outcomes, offering a new avenue for patients whose cancers are resistant to existing treatments.

What evidence suggests that this trial's treatments could be effective for pancreatic and ovarian cancer?

In this trial, participants will receive a combination of elimusertib and gemcitabine. Research has shown that combining elimusertib with chemotherapy could effectively fight cancer. Elimusertib, a type of drug, has slowed tumor growth in various studies, helping to prevent cancer progression for about 3.45 months. Gemcitabine, a chemotherapy drug, is known for extending the lives of people with advanced pancreatic cancer. Together in this trial, these treatments might enhance each other's effects to fight cancer more effectively. ^{1 3 4 6 7}

Who Is on the Research Team?

James M Cleary

Principal Investigator

Dana-Farber - Harvard Cancer Center LAO

Are You a Good Fit for This Trial?

Adults with advanced pancreatic, ovarian, or other solid tumors that have spread and are not curable by standard treatments. Participants must have measurable disease, may have had prior gemcitabine treatment, and should not exceed two lines of cytotoxic chemotherapy. HIV-positive patients on effective therapy can join. Women of childbearing potential and men must use contraception during the trial.

Inclusion Criteria

Your AST and ALT levels in your blood should not be more than 3 times the normal range set by the hospital.

I have advanced pancreatic or high-grade serous ovarian cancer that cannot be cured with standard treatments.

My chemotherapy within 6 months of cancer recurrence counts as one treatment line.

Exclusion Criteria

I do not have any stomach or intestine problems that affect how I absorb medication.

I do not have untreated brain metastases.

I am not pregnant or breastfeeding.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Dose Escalation

Evaluate the safety and tolerability of gemcitabine in combination with elimusertib and determine the maximum tolerated dose

Up to completion of dose-escalation phase

Visits on days 1, 2, 8, 9-10 of each cycle

Dose Expansion

Patients receive gemcitabine and elimusertib with additional biopsies and imaging scans to assess response

Cycles repeat every 21 days

Medical imaging after cycle 2 and every 9 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• BAY 1895344
• Biopsy
• Gemcitabine

Trial Overview The trial is testing a combination of gemcitabine (a chemotherapy drug) with elimusertib (an ATR inhibitor) to see if it's safe, find the best dose, and observe its effectiveness against advanced cancers like pancreatic and ovarian cancer. The goal is to determine whether this combo can shrink or stabilize tumors.

How Is the Trial Designed?

Group I: Treatment (gemcitabine, elimusertib) Experimental Treatment 5 Interventions

Patients receive gemcitabine IV over 30 minutes on days 1 and 8 and elimusertib QD or PO BID on days 2-3 and 9-10. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. All patients also undergo medical imaging scans after cycle 2 and then every 9 weeks throughout the trial and collection of blood samples during screening and on days 1, 2, and 9-10 of cycle 1. Patients in the dose-expansion portion of the trial also undergo biopsies during screening and on day 9 of cycle 1.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

The maximum tolerated dose (MTD) of gemcitabine when combined with gefitinib for patients with advanced pancreatic adenocarcinoma was determined to be 1,200 mg/m², with the treatment being feasible and tolerable.

Toxicity was mainly hematologic, with significant side effects including Grade 3 and 4 granulocytopenia, but no objective responses were observed in the patients, indicating that while the combination is manageable, it may not be effective in improving outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trial of fixed dose rate infusion gemcitabine with gefitinib in patients with pancreatic carcinoma. Carneiro, BA., Brand, RE., Fine, E., et al.[2022]

A combination of gemcitabine and erlotinib has been shown to provide a survival advantage in patients with locally advanced and metastatic pancreatic cancer compared to gemcitabine alone, highlighting its efficacy in a disease known for poor outcomes.

Erlotinib, a tyrosine kinase inhibitor targeting the epidermal growth factor receptor, demonstrates anti-tumor activity when used alongside gemcitabine, suggesting a promising mechanism of action in treating pancreatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of erlotinib in the management of pancreatic cancer. Starling, N., Neoptolemos, J., Cunningham, D.[2021]

In a phase 3 study involving 800 patients with metastatic pancreatic cancer, ganitumab combined with gemcitabine did not improve overall survival (OS) compared to gemcitabine alone, with median OS of 7.2 months for placebo and similar results for both ganitumab doses (7.0 and 7.1 months).

The combination treatment showed manageable safety with no unexpected toxicities, but circulating biomarkers did not indicate any treatment effect on OS or progression-free survival (PFS).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 3 randomized, double-blind, placebo-controlled trial of ganitumab or placebo in combination with gemcitabine as first-line therapy for metastatic adenocarcinoma of the pancreas: the GAMMA trial. Fuchs, CS., Azevedo, S., Okusaka, T., et al.[2022]

The combination of galunisertib and gemcitabine showed an acceptable safety profile in a phase 1b study with 7 Japanese patients, as no dose-limiting toxicities were reported, although all patients experienced at least one treatment-emergent adverse event.

The treatment demonstrated preliminary efficacy, with a clinical response rate of 42.9% and a median progression-free survival of 64 days, indicating potential benefits for patients with advanced or metastatic pancreatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1b study of galunisertib in combination with gemcitabine in Japanese patients with metastatic or locally advanced pancreatic cancer. Ikeda, M., Takahashi, H., Kondo, S., et al.[2022]

The combination of gemcitabine, capecitabine, bevacizumab, and erlotinib showed promising efficacy in treating advanced pancreatic cancer, with 10 partial responses observed among 20 patients and median overall survival of 12.5 months.

The maximum-tolerated dose of capecitabine was determined to be 1,660 mg/m², with a recommended dose of 1,440 mg/m² for further studies, while the treatment was generally well-tolerated with manageable side effects like diarrhea and skin rash.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose finding and early efficacy study of gemcitabine plus capecitabine in combination with bevacizumab plus erlotinib in advanced pancreatic cancer. Starling, N., Watkins, D., Cunningham, D., et al.[2022]

Citations

1. 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)

2. aacrjournals.org aacrjournals.org/mct/article/24/9/1402/764268/Efficacy-of-ATR-Kinase-Inhibitor-Elimusertib

Efficacy of ATR Kinase Inhibitor Elimusertib Monotherapy or ... Of 21 PDX models tested, 11 had significant prolongation of EFS-2 with elimusertib monotherapy. Four models had a PR and four had SD. PR/SD was observed in two ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.3076

A phase I study of ATR inhibitor BAY1895344 (elimusertib) ... Median progression-free survival in the RP2D cohort was 3.45 months. PK studies are in process and results will be presented at time of meeting.

4. sciencedirect.com sciencedirect.com/science/article/pii/S0925443924006197

ATR inhibition promotes synergistic antitumor effect in ... Combination treatment with BAY 1895344 and oxaliplatin exhibited a synergistic effect on both PC cell lines, with the effect being more pronounced on Capan-2.

5. dana-farber.org dana-farber.org/clinical-trials/21-727

A Phase 1/2 Study of BAY 1895344 (elimusertib, IND ... This phase I/II trial tests the safety, best dose, and whether elimusertib works in treating patients with solid tumors that have come back (relapsed) or ...

6. dana-farber.org dana-farber.org/clinical-trials/21-149

Phase 1 Trial of Gemcitabine Combined with the ... This phase I trial identifies the best dose, possible benefits and/or side effects of gemcitabine in combination with elimusertib (BAY 1895344) in treating ...

7. withpower.com withpower.com/trial/phase-1-peritoneal-neoplasms-1-2021-ceed0

Elimusertib + Chemotherapy for Pancreatic and Ovarian Cancer This phase I trial identifies the best dose, possible benefits and/or side effects of gemcitabine in combination with elimusertib (BAY 1895344) in treating ...