14 Participants Needed

Elimusertib + Chemotherapy for Pancreatic and Ovarian Cancer

Recruiting at 2 trial locations
Age: 18+
Sex: Any
Trial Phase: Phase 1
Sponsor: National Cancer Institute (NCI)
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Trial Summary

What is the purpose of this trial?

This phase I trial identifies the best dose, possible benefits and/or side effects of gemcitabine in combination with elimusertib (BAY 1895344) in treating patients with pancreatic, ovarian, and other solid tumors that have spread to other places in the body (advanced). Gemcitabine is a chemotherapy drug that blocks the cell from making DNA and may kill tumor cells. elimusertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving gemcitabine and elimusertib in combination may shrink or stabilize cancer.

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.

What data supports the effectiveness of the drug Elimusertib + Chemotherapy for Pancreatic and Ovarian Cancer?

The research shows that gemcitabine, a component of the treatment, has been used effectively in combination with other drugs like erlotinib and nimotuzumab for advanced pancreatic cancer, suggesting potential benefits when combined with other agents.12345

Is the combination of Elimusertib and chemotherapy safe for humans?

Gemcitabine, a part of the chemotherapy regimen, has been studied in various combinations for pancreatic and ovarian cancer, showing acceptable safety and tolerability in humans. These studies suggest that gemcitabine can be safely used with other drugs, although specific safety data for Elimusertib is not provided.36789

What makes the drug Elimusertib + Chemotherapy unique for treating pancreatic and ovarian cancer?

Elimusertib combined with chemotherapy, including gemcitabine, is unique because it potentially offers a novel approach by targeting specific cancer pathways, which may enhance the effectiveness of standard chemotherapy. This combination could provide a new option for patients with pancreatic and ovarian cancer, where traditional treatments have limited success.23101112

Research Team

JM

James M Cleary

Principal Investigator

Dana-Farber - Harvard Cancer Center LAO

Eligibility Criteria

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.
See 29 more

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.
See 15 more

Timeline

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)

Treatment Details

Interventions

  • BAY 1895344
  • Biopsy
  • Gemcitabine
Trial OverviewThe 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.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Treatment (gemcitabine, elimusertib)Experimental Treatment5 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.

Find a Clinic Near You

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials
14,080
Recruited
41,180,000+

Findings from Research

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).
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 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.
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]
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.
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]

References

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. [2022]
Erlotinib Plus Gemcitabine Compared With Gemcitabine Alone in Patients With Advanced Pancreatic Cancer: A Phase III Trial of the National Cancer Institute of Canada Clinical Trials Group. [2023]
Phase I trial of fixed dose rate infusion gemcitabine with gefitinib in patients with pancreatic carcinoma. [2022]
Gemcitabine combined with the monoclonal antibody nimotuzumab is an active first-line regimen in KRAS wildtype patients with locally advanced or metastatic pancreatic cancer: a multicenter, randomized phase IIb study. [2022]
Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. [2023]
Phase 1b study of galunisertib in combination with gemcitabine in Japanese patients with metastatic or locally advanced pancreatic cancer. [2022]
Patient self-reporting of tolerability using PRO-CTCAE in a randomized double-blind, placebo-controlled phase II trial comparing gemcitabine in combination with adavosertib or placebo in patients with platinum resistant or refractory epithelial ovarian carcinoma. [2023]
Gemcitabine in elderly patients with advanced pancreatic cancer. [2022]
Dose finding and early efficacy study of gemcitabine plus capecitabine in combination with bevacizumab plus erlotinib in advanced pancreatic cancer. [2022]
Role of erlotinib in the management of pancreatic cancer. [2021]
Management of advanced pancreatic cancer with gemcitabine plus erlotinib: efficacy and safety results in clinical practice. [2022]
Anti-tumour activity of afatinib, an irreversible ErbB family blocker, in human pancreatic tumour cells. [2021]