A Phase 1 Trial of the ATR Inhibitor BAY 1895344 in Combination With Cisplatin and With Cisplatin Plus Gemcitabine in Advanced Solid Tumors With an Emphasis on Urothelial Carcinoma

Who is this study for? Adult patients with advanced solid tumors
What treatments are being studied? BAY 1895344
Status: Active_not_recruiting
Location: See all (8) locations...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 1
SUMMARY

This phase I trial identifies the best dose, possible benefits and/or side effects of BAY 1895344 in combination with chemotherapy in treating patients with solid tumors or urothelial cancer that has spread to other places in the body (advanced). BAY 1895344 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Cisplatin and gemcitabine are chemotherapy drugs that stop the growth of tumor cells by killing the cells. Combining BAY 1895344 with chemotherapy treatment (cisplatin, or cisplatin and gemcitabine) may be effective for the treatment of advanced solid tumors, including urothelial cancer.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:

• Histologically-confirmed advanced solid tumor with measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 criteria, for which cisplatin-based therapy would be considered appropriate, including:

‣ Non-small cell lung cancer (NSCLC)

⁃ UC

⁃ Penile cancer

⁃ Malignant pleural mesothelioma

⁃ Small cell lung cancer

⁃ Biliary tract cancer

⁃ Esophageal and gastric cancers

⁃ Ovarian cancer

⁃ Endometrial cancer

⁃ Cervical cancer

⁃ Head and neck cancer

⁃ Triple-negative breast cancer (Her2/neu-negative, estrogen receptor \[ER\]/progesterone receptor \[PR\]-negative breast cancer)

• For the expansion cohort of the triplet combination at MTD/RP2D only:

‣ Patients with histologically confirmed advanced or unresectable urothelial carcinoma are eligible

⁃ The histology should be predominantly urothelial (\>= 50% of sample evaluated contains urothelial histology)

• Age \>= 18 years. Because no dosing or adverse event data are currently available on the use of BAY 1895344 in combination with gemcitabine and cisplatin in patients \< 18 years of age, children are excluded from this study

• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)

• Availability of archival FFPE tissue

• Prior cisplatin exposure of \< 300 mg/m\^2. Patients with prior cisplatin treatment must have received last cisplatin treatment \> 6 months prior to enrollment

• Prior treatment with PARP inhibitors is permitted (such as olaparib, rucaparib, or other experimental inhibitors of PARP administered in a clinical trial)

• Prior immune checkpoint inhibitor therapy is permitted (including anti-programmed cell death protein 1 \[PD-1\], anti-PD-ligand \[L\]1 therapy, such as pembrolizumab, nivolumab, avelumab, durvalumab, atezolizumab, or anti-cytotoxic t-lymphocyte protein 4 \[CTLA4\] therapy such as ipilimumab, or other experimental immune checkpoint pathway inhibitors administered in a clinical trial)

• Leukocytes \>= 3,000/mcL

• Hemoglobin \>= 9 g/dL

• Neutrophil count \>= 1,500/mcL

• Platelets \>= 100,000/mcL

• Total bilirubin =\< 2 mg/dL

• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) =\< 3 x institutional upper limit of normal (ULN)

• Creatinine clearance \>= 40 mL/min OR glomerular filtration rate (GFR) \>= 40 mL/min/1.73 m\^2 unless data exists supporting safe use at lower kidney function values, no lower than 30 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 are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression

• Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy; patients with stable brain metastases that are asymptomatic and on a stable dose of steroids are also considered eligible

• Patients with known history or current 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 BAY 1895344, cisplatin, and gemcitabine on the developing human fetus are unknown. For this reason and because deoxyribonucleic acid (DNA)-damage response inhibitors 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 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 BAY 1895344 administration

• Ability to understand and the willingness to sign a written informed consent document

Locations
United States
California
University of California Davis Comprehensive Cancer Center
Sacramento
Maryland
National Cancer Institute Developmental Therapeutics Clinic
Bethesda
National Institutes of Health Clinical Center
Bethesda
New York
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York
Ohio
Ohio State University Comprehensive Cancer Center
Columbus
Pennsylvania
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh
Wisconsin
University of Wisconsin Carbone Cancer Center - University Hospital
Madison
Other Locations
Canada
University Health Network-Princess Margaret Hospital
Toronto
Time Frame
Start Date: 2021-08-25
Completion Date: 2026-06-30
Participants
Target number of participants: 74
Treatments
Experimental: Arm I (cisplatin, elimusertib)
Patients receive cisplatin IV over 1-2 hours on day 1 and 8, and elimusertib PO QD on days 2 and 9. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
Experimental: Arm II (cisplatin, gemcitabine, elimusertib)
Patients receive cisplatin IV over 1-2 hours on day 1 and 8, gemcitabine IV over 30 minutes on days 1 and 8, and elimusertib PO QD on days 2 and 9. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
Sponsors
Leads: National Cancer Institute (NCI)

This content was sourced from clinicaltrials.gov

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