Testing the Addition of an Anti-cancer Drug, Elimusertib (BAY 1895344) ATR Inhibitor, to the Chemotherapy Treatment (Gemcitabine) for Advanced Pancreatic and Ovarian Cancer, and Advanced Solid Tumors
Phase 1 Trial of Gemcitabine Combined With the Elimusertib (BAY 1895344) ATR Inhibitor With Expansion Cohorts in Advanced Pancreatic and Ovarian Cancer
3 other identifiers
interventional
14
1 country
3
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Jun 2021
Longer than P75 for phase_1
3 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 4, 2020
CompletedFirst Posted
Study publicly available on registry
November 5, 2020
CompletedStudy Start
First participant enrolled
June 1, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 1, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
May 20, 2026
ExpectedMay 22, 2025
May 1, 2025
3.8 years
November 4, 2020
May 21, 2025
Conditions
Outcome Measures
Primary Outcomes (6)
Incidence of adverse events
The toxicity of the combination of gemcitabine plus elimusertib will be assessed with Common Terminology Criteria for Adverse Events (CTCAE) v. 5.0 criteria.
Up to 1 year
Maximum tolerated dose (MTD)
A conventional algorithm (3+3 design) will be used to identify the MTD, escalating on zero of three or one of six dose-limiting toxicities (DLTs), and de-escalating if two DLTs are encountered. The MTD will be the highest dose level at which zero of three or one of six subjects experience a DLT.
Up to completion of dose-escalation phase
Overall response rate (ORR) (expansion cohort)
Radiological response will be assessed with Response Evaluation Criteria in Solid Tumors 1.1 criteria and will be graded as complete response (CR), partial response (PR), stable disease and progressive disease.
Up to 1 year
Duration of response (expansion cohort)
Time at which measurement criteria are met for CR or PR (whichever is first recorded) until the first date on which recurrent or progressive disease is objectively documented, assessed up to 1 year
Progression free survival (PFS) (expansion cohort)
Time from study enrollment until the identification of disease progression or death, assessed up to 1 year
Overall survival (expansion cohort)
Time from study enrollment until death due to any cause, assessed up to 1 year
Secondary Outcomes (7)
Pharmacokinetic (PK) profile of elimusertib in combination with gemcitabine
Day 1 of dose-escalation phase
Gemcitabine pharmacokinetics
Days 1 and 8 of dose-escalation
Presence or absence of homologous recombination (HR) repair proficiency
Pre-treatment to time of disease progression, assessed up to 1 year
Presence or absence of replication stress
Pre-treatment to time of disease progression, assessed up to 1 year
Presence or absence of ATR activation
Pre-treatment to time of disease progression, assessed up to 1 year
- +2 more secondary outcomes
Other Outcomes (1)
Pharmacodynamic (biological endpoints, toxicity and efficacy) parameters
Up to 30 days
Study Arms (1)
Treatment (gemcitabine, elimusertib)
EXPERIMENTALPatients 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.
Interventions
Undergo biopsy (dose expansion cohort only)
Undergo collection of blood samples
Undergo medical imaging scans
Given PO
Given IV
Eligibility Criteria
You may qualify if:
- DOSE ESCALATION COHORT:
- Patients must have histologically confirmed solid tumor malignancy that is not curable with standard approaches. Gemcitabine must be considered a standard therapy for the participant's malignancy
- Patients must have a measurable disease, in at least one lesion, for both the dose escalation and expansion cohorts, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1
- Patients must have received one line of treatment for their incurable cancer before enrolling in this trial. Patients with rare malignancies for which there is no accepted standard chemotherapy regimen can enroll without any prior treatments
- Patients must not have received more than two lines of cytotoxic chemotherapy
- Patients can have received prior gemcitabine
- Adjuvant chemotherapy is counted as one line of treatment if patients received it within 6 months of their cancer recurring
- There is no limit for lines of prior targeted therapies or immunotherapy
- Patients who received a prior PARP inhibitor must have had progressive disease, or intolerable toxicity, on the PARP inhibitor prior to enrolling on the study
- DOSE EXPANSION COHORT:
- Participants must have a histologically confirmed advanced pancreatic adenocarcinoma or ovarian cancer (high grade serous ovarian, primary peritoneal or fallopian tube cancer) that is not curable with standard approaches. Patients with both metastatic pancreatic cancer and unresectable pancreatic cancer are eligible
- Ovarian cancer:
- Patients with ovarian cancer must have platinum-resistant disease, defined as progression within 6 months after the last platinum regimen
- Patients with ovarian cancer cannot have received more than one prior regimen in the platinum-resistance setting
- Pancreatic cancer:
- +23 more criteria
You may not qualify if:
- Patients cannot receive chemotherapy, targeted therapy or immunotherapy within 3 weeks of study entry
- Patients who have had radiotherapy within 4 weeks prior to entering the study
- Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 1) with the exception of alopecia and lymphopenia
- Participants must not have received investigational therapy administered =\< 4 weeks or within a time interval less than at least five half-lives of the investigational agent, whichever is longer, before initiation of protocol therapy
- Participants with known untreated brain metastases are excluded from this clinical trial
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to elimusertib (BAY 1895344) or gemcitabine
- Patients receiving any medications that are substrates of CYP3A4 with a narrow therapeutic window, or strong inhibitors/inducers of CYP3A4 are ineligible, if they cannot be transferred to alternative medication. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
- Patients with uncontrolled intercurrent illness including but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, clinically significant cardiac arrhythmia, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome or psychiatric illness/social situations that would limit compliance with study requirements are excluded
- Patients with psychiatric illness/social situations that would limit compliance with study requirements
- Pregnant women are excluded from this study because elimusertib (BAY 1895344) as a DNA-damage response inhibitor, and gemcitabine may have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with elimusertib (BAY 1895344) breastfeeding should be discontinued if the mother is treated with elimusertib (BAY 1895344) and for 4 months after end of treatment. These potential risks may also apply to other agents used in this study
- Patients who have successfully undergone treatment for another, unrelated clinically relevant cancer, \>= 3 years post final treatment, are eligible to participate in this study
- Patients cannot have received radiation to more than 25% of their hematopoietically active bone marrow. Pelvic radiation is considered to affect 25% of the haematopoietically active bone marrow, and only one prior course of pelvic radiation is allowed (Hayman et al., 2011)
- Patients previously treated with an ATR inhibitor are excluded
- Participants who have undergone major surgery =\< 4 weeks before initiating protocol therapy must have sufficiently recovered from adverse events caused by the procedure, as judged by the treating investigator
- Subjects with a gastrointestinal disorder or malabsorption that could potentially affect the absorption of the study drug are excluded
- +3 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (3)
National Cancer Institute Developmental Therapeutics Clinic
Bethesda, Maryland, 20892, United States
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
James M Cleary
Dana-Farber - Harvard Cancer Center LAO
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 4, 2020
First Posted
November 5, 2020
Study Start
June 1, 2021
Primary Completion
April 1, 2025
Study Completion (Estimated)
May 20, 2026
Last Updated
May 22, 2025
Record last verified: 2025-05
Data Sharing
- IPD Sharing
- Will share
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.