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AzTrials

Advanced Fallopian Tube CarcinomaPhase 1NCT04616534

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

A Phase 1 study testing Biopsy Procedure, Biospecimen Collection and Diagnostic Imaging Testing in people with Advanced Fallopian Tube Carcinoma and Advanced Malignant Solid Neoplasm, run by National Cancer Institute (NCI) at 3 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Biopsy Procedure, Biospecimen Collection and Diagnostic Imaging Testing
Could I receive a placebo?
No, everyone receives an active treatment
How many people
14 participants
Where
3 sitesUnited States
Study dates
1 Jun 2021to 20 May 2027
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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:
  • Patients with pancreatic cancer cannot have received more than one line of cytotoxic chemotherapy in the metastatic setting
  • Adjuvant chemotherapy is not counted as one line of treatment, if patients received it more than 6 months prior to their cancer recurring
  • Patients must have a biopsiable disease and at least one separate measurable lesion
  • DOSE ESCALATION AND EXPANSION COHORTS:
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
  • Age >= 18 years
  • Because no dosing or adverse event data are currently available on the use of elimusertib (BAY 1895344) in combination with gemcitabine in patients < 18 years of age, children are excluded from this study
  • Leukocytes >= 3,000/mcL
  • Hemoglobin >= 10 g/dL (no red blood cell transfusion is allowed within 3 weeks before starting the trial)
  • Neutrophil count >= 1,500 K/mcL (participants must not have received colony stimulating factors [e.g., granulocyte colony-stimulating factor, granulocyte macrophage colony stimulating factor or recombinant erythropoietin] within 3 weeks before initiation of protocol therapy)
  • Platelets >= 100,000 /mcL
  • Albumin >= 2.8 mg/dL
  • Total bilirubin =< 1.5 x institutional upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) / alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 3 x institutional ULN
  • Creatinine clearance =< 1.5 x institutional ULN OR glomerular filtration rate (GFR) >= 50 mL/min/1.73 m^2
  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
  • For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
  • Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
  • Patients with treated brain metastases or primary brain tumors are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression for >= 4 weeks after the last date of treatment are permitted, and if they are no longer taking corticosteroids for at least 4 weeks prior to beginning the protocol
  • Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial with permission of the principal investigator of the trial
  • Patients with known history or current clinically significant symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association functional classification. To be eligible for this trial, patients should be class 2B or better
  • The effects of elimusertib (BAY 1895344) on the developing human fetus are unknown. For this reason and because DNA-damage response inhibitor agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation and for 6 months after completion of elimusertib (BAY 1895344) administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 6 months after completion of elimusertib (BAY 1895344) administration
  • Ability to understand and the willingness to sign a written informed consent document

Who cannot join

  • 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
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  • 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
  • Participants with a history of a clinically relevant second primary malignancy within the past 2 years are excluded. Exceptions include resected basal and squamous cell carcinomas of the skin and completely resected carcinoma in situ of any type
  • Patients not able to swallow tablets
  • For the Dose Expansion Cohort, patients who cannot safely undergo tumor biopsies are excluded

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • National Cancer Institute Developmental Therapeutics Clinic

    Bethesda, Maryland, 20892

  • National Institutes of Health Clinical Center

    Bethesda, Maryland, 20892

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

Other trials in United States

About this study

Official title: Phase 1 Trial of Gemcitabine Combined With the Elimusertib (BAY 1895344) ATR Inhibitor With Expansion Cohorts in Advanced 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 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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Evaluate the safety and tolerability of gemcitabine in combination with elimusertib (BAY 1895344), as assessed by Common Terminology Criteria for Adverse Events (CTCAE) 5.0. (Dose Escalation and Expansion Cohort) II. Determine the maximum tolerated dose (MTD) of gemcitabine in combination with elimusertib (BAY 1895344). (Dose Escalation Cohort)

SECONDARY OBJECTIVES:

  1. To observe and record anti-tumor activity. II. Analyze the pharmacokinetic (PK) profile of the gemcitabine and elimusertib (BAY 1895344) combination.

III. Assessing whether immunohistochemical markers of deoxyribonucleic acid (DNA) damage, gamma-H2AX and phosphorylated (p)NBS1, increase in on-treatment biopsies compared to the levels seen in pre-treatment biopsies.

EXPLORATORY OBJECTIVES:

  1. Explore biomarkers that predict response to this combination. II. Evaluate mechanisms of acquired resistance to this combination.

OUTLINE: This is a dose-escalation study of gemcitabine followed by a dose expansion study.

Patients receive gemcitabine intravenously (IV) over 30 minutes on days 1 and 8 and elimusertib orally (PO) once daily (QD) or twice daily (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.

After completion of study treatment, patients are followed up for 30 days.

Being tested
Biopsy Procedure, Biospecimen Collection, Diagnostic Imaging Testing, Elimusertib, Gemcitabine
Medical subject headings
Pancreatic Neoplasms, Fallopian Tube Neoplasms, Ovarian Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Biopsy ProcedureProcedure or surgery

    Also called Biopsy, BIOPSY_TYPE, Bx

    Undergo biopsy (dose expansion cohort only)

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

    Undergo collection of blood samples

  • Diagnostic Imaging TestingProcedure or surgery

    Also called Diagnostic Imaging, Medical Imaging

    Undergo medical imaging scans

  • ElimusertibDrug

    Also called ATR Inhibitor BAY1895344, ATR Kinase Inhibitor BAY1895344, BAY 1895344, BAY-1895344

    Given PO

  • GemcitabineDrug

    Also called dFdC, dFdCyd, Difluorodeoxycytidine

    Given IV

Study groups in NCT04616534
Study groupRoleWhat they receive
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.
Receives: Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Diagnostic Imaging Testing; Drug: Elimusertib; Drug: Gemcitabine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Patients on Treatment With Related 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.

    The safety and tolerability were evaluated using the number of treatment-related adverse events.

    Measured: Adverse events were recorded between the first patient treated (June 2021) and 30 days out from the last patient ending treatment (October 2024) (3 years and 4 months). Adverse events were collected for a median of 88.5 days, ranging 58 - 315 days.

  2. 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.

    The MTD was not reached due to toxicity experienced during cycle 1.

    Measured: The MTD was evaluated during the dose-escalation phase, occurring from the first patient on treatment (Jun '21) through the last patient's last dose (Sep '24) (3 years and 3 months). MTD was evaluated for a median of 58.5 days, ranging 28 - 285 days.

  3. Overall Response Rate (ORR)

    Radiological response will be assessed with Response Evaluation Criteria in Solid Tumors 1.1 criteria and will be portrayed as the percentage of subjects with a complete response (CR) and partial response (PR).

    Measured: ORR was assessed from the time of the first patient on study (June 2021) through the last patient off study (October 2024). ORR was calculated for a median of 103 days, ranging from 30 - 312 days.

  4. Duration of Response

    Measured: Duration of response was assessed from the time of the first patient on treatment (June 2021) through the last patient off study (October 2024). Duration of response was calculated for a median of 103 days, ranging from 30 - 312 days.

  5. Progression Free Survival (PFS)

    Measured: PFS was evaluated from the first patient on study (Jun '21) through the last patient's death or date of progressive disease (Sep '24) (3 years and 3 months). PFS was calculated for a median of 90 days, ranging 25 - 286 days.

  6. Overall Survival

    Overall survival (OS) was evaluated from the first patient on study (June 2021) through the last patient's death or off study date (October 2024).

    Measured: OS was calculated for a median of 103 days, ranging from 30 - 312 days.

Secondary outcomes (9)

  1. Pharmacokinetic (PK) Profile of Elimusertib in Combination With Gemcitabine

    Individual PK parameters will be estimated for the maximum concentration (Cmax), as feasible with non-compartmental methods. The PK variables will be tabulated, and descriptive statistics (e.g., geometric means and coefficients of variation) will be calculated for each dose level. PK parameters will be reported descriptively.

    Measured: Day 1 of dose-escalation phase (first patient's day 1, June 2021, to last patient's day 1, December 2023) equaling the total collection time of 2 year and 6 months. PK samples for collected on a single day for each participant.

  2. Gemcitabine Pharmacokinetics

    The CDA phenotype will be correlated with gemcitabine half-life, AUC and the dFdU/gemcitabine metabolic ratio.

    Measured: Days 1 and 8 of cycle 1 dose-escalation (first patient's day 1, June 2021, to last patient's day 8, December 2023) equaling the total collection time of 2 year and 6 months. Samples were collected on two days for each participant.

  3. Presence or Absence of Homologous Recombination (HR) Repair Proficiency (Dose Expansion)

    Will be defined according to formation of RAD51 foci. Will also be evaluated in relation to the clinical outcomes of ORR and PFS time.

    Measured: Pre-treatment to time of disease progression, assessed up to 1 year in the dose expansion cohort

  4. Presence or Absence of ATR Activation (Dose Expansion)

    Will be defined by the expression of pATR and pCHK1. Will also be evaluated in relation to the clinical outcomes of ORR and PFS time.

    Measured: Pre-treatment to time of disease progression, assessed up to 1 year in the dose expansion cohort

  5. Increase in Deoxyribonucleic Acid (DNA) Damage Level (Dose Expansion)

    Changes in immunohistochemical markers of DNA damage, gamma-H2AX and phosphorylated (p)NBS1.

    Measured: Pre-treatment and on-treatment in the dose expansion cohort

  6. Conversion of Cancer With Stable Replication Forks to One With Unstable Replication Forks (Dose Expansion)

    DNA fiber assays will be used to assess whether gemcitabine/elimusertib treatment converts a cancer with stable replication forks to one with unstable replication forks. Will also be evaluated in relation to the clinical outcomes of ORR and PFS time.

    Measured: Pre-treatment to time of disease progression, assessed up to 1 year in the dose expansion cohort

  7. Presence or Absence of Replication Stress (Dose Expansion)

    Will be defined at the gene expression and protein levels for phosphorylated (p)KAP1, pRPA32, cyclin E and MYC. Will also be evaluated in relation to the clinical outcomes of ORR and PFS time.

    Measured: Pre-treatment to time of disease progression, assessed up to 1 year in the dose expansion cohort.

  8. Pharmacokinetic (PK) Profile of Elimusertib in Combination With Gemcitabine

    Individual PK parameters will be estimated for the area under the concentration-time curve (AUC), as feasible with non-compartmental methods. The PK variables will be tabulated, and descriptive statistics (e.g., geometric means and coefficients of variation) will be calculated for each dose level. PK parameters will be reported descriptively.

    Measured: Day 1 of dose-escalation phase (first patient's day 1, June 2021, to last patient's day 1, December 2023) equaling the total collection time of 2 year and 6 months. PK samples for collected on a single day for each participant.

  9. Pharmacokinetic (PK) Profile of Elimusertib in Combination With Gemcitabine

    Individual PK parameters will be estimated for the half-life (t1/2), apparent clearance (Cl/F) and apparent volume of distribution (V/F), as feasible with non-compartmental methods. The PK variables will be tabulated, and descriptive statistics (e.g., geometric means and coefficients of variation) will be calculated for each dose level. PK parameters will be reported descriptively.

    Measured: Day 1 of dose-escalation phase (first patient's day 1, June 2021, to last patient's day 1, December 2023) equaling the total collection time of 2 year and 6 months. PK samples for collected on a single day for each participant.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Nov 2020
  2. Study start1 Jun 2021
  3. Primary completion1 Apr 2025
  4. Study completion20 May 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
14 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04616534
Sponsor's protocol ID
NCI-2020-08370
Other IDs
NCI-2020-08370, 10403, 10403, UM1CA186709
Status last verified
May 2026
First submitted
4 Nov 2020
Last updated
31 Jul 2026
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Biopsy Procedure, Biospecimen Collection and Diagnostic Imaging Testing in people with Advanced Fallopian Tube Carcinoma and Advanced Malignant Solid Neoplasm, run by National Cancer Institute (NCI) at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 38 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 31 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 9 Jul 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Patients on Treatment With Related Adverse Events (time frame: Adverse events were recorded between the first patient treated (June 2021) and 30 days out from the last patient ending treatment (October 2024) (3 years and 4 months). Adverse events were collected for a median of 88.5 days, ranging 58 - 315 days.). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04616534.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jul 2026.

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