Status and phase
Conditions
Treatments
Study type
Funder types
Identifiers
About
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.
Full description
PRIMARY OBJECTIVES:
I. To establish the safety and tolerability of the combination of cisplatin + elimusertib (BAY 1895344) in patients with advanced solid tumors.
II. To establish the safety and tolerability of the combination of cisplatin + gemcitabine + BAY 1895344 in patients with advanced solid tumors with an emphasis on urothelial carcinoma (UC).
III. To establish the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of cisplatin + BAY 1895344 and cisplatin + gemcitabine + BAY 1895344.
SECONDARY OBJECTIVES:
I. To evaluate the pharmacokinetic profile of BAY 1895344 (in the doublet and triplet combinations) and gemcitabine (in the triplet) in combination with cisplatin.
II. To further evaluate the toxicity of the combination of cisplatin + gemcitabine + BAY 1895344 in patients with UC.
III. To evaluate preliminary efficacy observed with cisplatin + BAY 1895344 and cisplatin + gemcitabine + BAY 1895344 in patients with advanced solid tumors, including UC.
IV. To monitor for tumor response and symptom relief in addition to safety and tolerability.
V. To evaluate the association between ATM expression by immunohistochemical staining and responses to therapy.
EXPLORATORY OBJECTIVES:
I. To evaluate the correlation of biomarkers, including deleterious deoxyribonucleic acid (DNA) damage response (DDR) gene alterations and circulating tumor (ct)DNA with responses to therapy using whole exome sequencing (WES) and messenger ribonucleic acid sequencing (RNA seq) analysis of archival formalin fixed paraffin embedded (FFPE) tissue, as well as blood.
II. To correlate drug exposure with response and/or toxicity.
OUTLINE: This is a dose-escalation study of elimusertib. Patients are assigned to 1 of 2 arms.
ARM I (DOUBLET COMBINATION): Patients receive cisplatin intravenously (IV) over 1-2 hours on day 1 and 8, and elimusertib orally (PO) once daily (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.
ARM II (TRIPLET COMBINATION): 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.
After completion of study treatment, patients are followed up at 30 days, then every 3 months thereafter.
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
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:
For the expansion cohort of the triplet combination at MTD/RP2D only:
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
Exclusion criteria
Primary purpose
Allocation
Interventional model
Masking
74 participants in 2 patient groups
Loading...
Data sourced from clinicaltrials.gov
Clinical trials
Research sites
Resources
Legal