Trials / Active Not Recruiting
Active Not RecruitingNCT04491942
Testing the Addition of an Anti-cancer Drug, BAY 1895344, to the Usual Chemotherapy Treatment (Cisplatin, or Cisplatin and Gemcitabine) for Advanced Solid Tumors With Emphasis on Urothelial Cancer
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
- Status
- Active Not Recruiting
- Phase
- Phase 1
- Study type
- Interventional
- Enrollment
- 74 (estimated)
- Sponsor
- National Cancer Institute (NCI) · NIH
- Sex
- All
- Age
- 18 Years
- Healthy volunteers
- Not accepted
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.
Detailed 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. 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.
Conditions
- Advanced Bile Duct Carcinoma
- Advanced Breast Carcinoma
- Advanced Cervical Carcinoma
- Advanced Endometrial Carcinoma
- Advanced Esophageal Carcinoma
- Advanced Gastric Carcinoma
- Advanced Head and Neck Carcinoma
- Advanced Lung Non-Small Cell Carcinoma
- Advanced Lung Small Cell Carcinoma
- Advanced Malignant Solid Neoplasm
- Advanced Ovarian Carcinoma
- Advanced Penile Carcinoma
- Advanced Pleural Malignant Mesothelioma
- Advanced Urothelial Carcinoma
- Anatomic Stage III Breast Cancer AJCC v8
- Anatomic Stage IV Breast Cancer AJCC v8
- Clinical Stage III Gastric Cancer AJCC v8
- Clinical Stage IV Gastric Cancer AJCC v8
- Stage III Cervical Cancer AJCC v8
- Stage III Distal Bile Duct Cancer AJCC v8
- Stage III Intrahepatic Bile Duct Cancer AJCC v8
- Stage III Lung Cancer AJCC v8
- Stage III Ovarian Cancer AJCC v8
- Stage III Penile Cancer AJCC v8
- Stage III Pleural Diffuse Malignant Mesothelioma AJCC v8
- Stage IV Cervical Cancer AJCC v8
- Stage IV Distal Bile Duct Cancer AJCC v8
- Stage IV Intrahepatic Bile Duct Cancer AJCC v8
- Stage IV Lung Cancer AJCC v8
- Stage IV Ovarian Cancer AJCC v8
- Stage IV Penile Cancer AJCC v8
- Stage IV Pleural Diffuse Malignant Mesothelioma AJCC v8
- Triple-Negative Breast Carcinoma
- Unresectable Urothelial Carcinoma
Interventions
| Type | Name | Description |
|---|---|---|
| DRUG | Cisplatin | Given IV |
| DRUG | Elimusertib | Given PO |
| DRUG | Gemcitabine Hydrochloride | Given IV |
Timeline
- Start date
- 2021-08-25
- Primary completion
- 2026-06-30
- Completion
- 2026-06-30
- First posted
- 2020-07-30
- Last updated
- 2026-04-13
Locations
8 sites across 2 countries: United States, Canada
Regulatory
- FDA-regulated drug study
Source: ClinicalTrials.gov record NCT04491942. Inclusion in this directory is not an endorsement.