Testing the Addition of an Anti-cancer Drug, BAY 1895344, to Usual Chemotherapy for Advanced Stage Solid Tumors, With a Specific Focus on Patients With Small Cell Lung Cancer, Poorly Differentiated Neuroendocrine Cancer, and Pancreatic Cancer
BAY 1895344 Plus Topoisomerase-1 (Top1) Inhibitors in Patients With Advanced Solid Tumors, Phase I Studies With Expansion Cohorts in Small Cell Lung Carcinoma (SCLC), Poorly Differentiated Neuroendocrine Carcinoma (PD-NEC) and Pancreatic Adenocarcinoma (PDA)
3 other identifiers
interventional
28
1 country
23
Brief Summary
This phase I trial tests the safety, side effects and best dose of BAY 1895344 when given together with usual chemotherapy (irinotecan or topotecan) in treating patients with solid tumors that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced), with a specific focus on small cell lung cancer, poorly differentiated neuroendocrine cancer, and pancreatic cancer. BAY 1895344 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Chemotherapy drugs, such as irinotecan and topotecan, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Adding BAY 1895344 to irinotecan or topotecan may be safe and tolerable in treating patients with advanced solid tumors.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Oct 2021
Longer than P75 for phase_1
23 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
August 14, 2020
CompletedFirst Posted
Study publicly available on registry
August 17, 2020
CompletedStudy Start
First participant enrolled
October 20, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 15, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
March 4, 2026
CompletedMarch 6, 2025
March 1, 2025
3.3 years
August 14, 2020
March 5, 2025
Conditions
Outcome Measures
Primary Outcomes (2)
Maximum tolerated dose (MTD) (Dose Escalation Phase)
Defined by occurrence of \>= 2 dose limiting toxicities (DLTs) defined as grade 4 neutropenia lasting \>= 7 days, grade 4 thrombocytopenia, grade 4 anemia, grade 3 neutropenia with fever, grade 3 thrombocytopenia with bleeding, any grade 3 hematologic toxicity lasting \>= 7 days (counting from first day of toxicity grade recognition) or any non-hematologic grade \>= 2 adverse events (AEs) lasting \>= 7 days (with the exception of grade 2 \[G2\] fatigue, G2 nausea or G2 diarrhea) (counting from first day of toxicity grade recognition) in any dose level during cycle 1 of treatment. DLTs will be graded by Common Terminology Criteria for Adverse Events version 5.0.
Up to 21 days
Occurrence of grade 4 hematologic AEs (Dose Expansion Phase)
Grade 4 hematologic toxicity will be monitored using the Bayesian approach of Thall, Simon, Estey as extended by Thall and Sung. Clinical safety data (e.g. AEs) will be tabulated and summarized using descriptive statistics as requested by the sponsor investigator, executive committee, medical monitor or Data Safety Monitoring Board using methods described in the Data Safety Monitoring Plan.
Up to 6 months post-treatment
Secondary Outcomes (8)
Objective response rate (ORR)
Up to 12 weeks
Duration of response (DOR)
From when a patient achieves disease control (complete response, partial response, stable disease) on a restaging scan to the time of radiographic progression, assessed up to 6 months post-treatment
Progression-free survival (PFS)
From when a patient starts treatment to when they demonstrate radiographic progression or succumb to the disease, assessed up to 6 months post-treatment
Overall survival (OS)
From when a patient starts treatment to the date they succumb to the disease, assessed up to 6 months post-treatment
Maximum concentration (Cmax)
Cycle 1, days 1, 2, 3, and 4
- +3 more secondary outcomes
Other Outcomes (2)
Tumor ATM expression loss
Baseline
Tumor deoxyribonucleic acid damage response (DDR) gene mutations present
Baseline
Study Arms (3)
Cohort I (elimusertib, irinotecan)
EXPERIMENTALPatients receive elimusertib PO BID on days 1 and 2 and irinotecan IV over 90 minutes on day 1 of each cycle. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT and/or MRI throughout the study, tumor biopsy at screening and on study, and collection of blood samples at screening.
Cohort II (elimusertib, irinotecan)
EXPERIMENTALPatients receive elimusertib PO QD on days 2, 3, 9, 10, 16, and 17 of cycle 1 and 2, and on days 2, 3, 9, and 10 of each cycle thereafter. Patients receive irinotecan IV over 90 minutes on days 1, 8, and 15 of cycle 1 and 2, and on days 1 and 8 of each cycle thereafter. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT and/or MRI throughout the study, tumor biopsy at screening and on study, and collection of blood samples at screening.
Cohort III (elimusertib, topotecan)
EXPERIMENTALPatients receive elimusertib PO QD on days 2 and 5 and topotecan IV over 30 minutes on days 1-5 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT and/or MRI throughout the study, tumor biopsy at screening and on study, and collection of blood samples at screening.
Interventions
Undergo tumor biopsy
Undergo collection of blood samples
Undergo CT
Given PO
Given IV
Undergo MRI
Given IV
Eligibility Criteria
You may qualify if:
- DOSE ESCALATION COHORTS: Patients must have a biopsy-proven solid tumor that is metastatic or unresectable and has progressed on at least one line of standard therapy
- DOSE ESCALATION COHORTS: Patients must have a solid tumor for which irinotecan or topotecan is considered standard of care
- DOSE EXPANSION COHORTS: Patients must have biopsy proven metastatic or unresectable small cell lung cancer (SCLC), poorly differentiated neuroendocrine carcinoma (PD-NEC) (any extrapulmonary neuroendocrine carcinoma with small cell or large cell histology) or pancreatic adenocarcinoma (PDA) and have progressed on at least one line of standard therapy
- DOSE EXPANSION COHORTS: Patients must have at least one measurable lesion outside of the lesion to be biopsied
- Patients must be able to swallow pills
- Age \>= 18 years. Because no dosing or adverse event data are currently available on the use of BAY 1895344 in combination with irinotecan or topotecan in patients \< 18 years of age, children are excluded from this study
- Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
- Hemoglobin \> 9 g/dL
- Absolute neutrophil count \>= 1,500/mcL
- Platelets \>= 100,000/mcL
- Total bilirubin =\< 2 x institutional upper limit of normal (ULN)
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 x institutional ULN (=\< 5 x institutional ULN if liver metastases present)
- Glomerular filtration rate (GFR) \>= 60 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
- +6 more criteria
You may not qualify if:
- Patients who have previously been treated with irinotecan will not be eligible to participate in the irinotecan arm and patients who have previously been treated with topotecan will not be eligible to participate in the topotecan arm. However, patients who previously received irinotecan may be treated with topotecan (and vice versa) should the other agent be considered a possible standard of care for their disease. Patients who have previously been treated with BAY 1895344 will be excluded from the study
- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) 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 endocrinopathies from prior immunotherapy
- Patients who are receiving any other investigational agents
- The investigator(s) must state a medical or scientific reason if patients who have brain metastases will be excluded from the study
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to BAY 1895344 or other agents used in study
- Patients receiving any medications or substances 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
- Patients with psychiatric illness/social situations that would limit compliance with study requirements
- Pregnant women are excluded from this study because BAY 1895344 is agent with 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 BAY 1895344, breastfeeding should be discontinued if the mother is treated with BAY 1895344. These potential risks may also apply to other agents used in this study
- Patients with an uncontrolled infection requiring IV antibiotics will not be eligible to participate in the study
- Patients on strong CYP3A4 inhibitors must discontinue them at least 1 week prior to starting irinotecan therapy
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (23)
Mayo Clinic Hospital in Arizona
Phoenix, Arizona, 85054, United States
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, 92868, United States
Yale University
New Haven, Connecticut, 06520, United States
Smilow Cancer Hospital Care Center-Trumbull
Trumbull, Connecticut, 06611, United States
Mayo Clinic in Florida
Jacksonville, Florida, 32224-9980, United States
University of Kansas Clinical Research Center
Fairway, Kansas, 66205, United States
University of Kansas Cancer Center
Kansas City, Kansas, 66160, United States
University of Kansas Cancer Center-Overland Park
Overland Park, Kansas, 66210, United States
University of Kansas Hospital-Indian Creek Campus
Overland Park, Kansas, 66211, United States
University of Kansas Hospital-Westwood Cancer Center
Westwood, Kansas, 66205, United States
Mayo Clinic in Rochester
Rochester, Minnesota, 55905, United States
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri, 63376, United States
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, 63141, United States
University of Kansas Cancer Center - North
Kansas City, Missouri, 64154, United States
University of Kansas Cancer Center - Lee's Summit
Lee's Summit, Missouri, 64064, United States
University of Kansas Cancer Center at North Kansas City Hospital
North Kansas City, Missouri, 64116, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Siteman Cancer Center-South County
St Louis, Missouri, 63129, United States
Siteman Cancer Center at Christian Hospital
St Louis, Missouri, 63136, United States
Montefiore Medical Center-Einstein Campus
The Bronx, New York, 10461, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232, United States
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, 37232, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Thatcher Heumann
Yale University Cancer Center LAO
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 14, 2020
First Posted
August 17, 2020
Study Start
October 20, 2021
Primary Completion
February 15, 2025
Study Completion
March 4, 2026
Last Updated
March 6, 2025
Record last verified: 2025-03
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.