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Active Not RecruitingNCT04514497

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)

Status
Active Not Recruiting
Phase
Phase 1
Study type
Interventional
Enrollment
28 (actual)
Sponsor
National Cancer Institute (NCI) · NIH
Sex
All
Age
18 Years
Healthy volunteers
Not accepted

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.

Detailed description

PRIMARY OBJECTIVES: I. To assess safety and tolerability of each of the elimusertib (BAY 1895344) plus topoisomerase 1 (top1) inhibitor (irinotecan hydrochloride \[irinotecan\] or topotecan hydrochloride \[topotecan\]) combinations. II. To estimate maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of each of the combinations. SECONDARY OBJECTIVES: I. To observe and record anti-tumor activity. II. To estimate objective response rate (ORR), progression free survival (PFS), overall survival (OS) and duration of response (DOR) in patients treated with each combination. III. To estimate plasma pharmacokinetic (PK) characteristics of BAY 1895344 plus each top1 inhibitor (irinotecan or topotecan) when used in combination. IV. To estimate changes in pharmacodynamic (PD) markers of deoxyribonucleic acid (DNA) damage (gamma-H2AX, phosphorylated \[p\]S343-NBS1) elicited by each combination from on-treatment tumor biopsies (in dose expansion cohorts only). EXPLORATORY OBJECTIVES: I. To estimate response outcomes (ORR, PFS, OS, DOR) in study patients by tumor ataxia telangiectasia mutated (ATM) expression loss (assessed by immunohistochemistry \[IHC\]). II. To estimate response outcomes (ORR, PFS, OS, DOR) in study patients with tumor DNA damage response (DDR) mutations (assessed by whole exome sequencing \[WES\], ribonucleic acid \[RNA\] sequencing \[RNA Seq\], and circulating tumor DNA \[ctDNA\] analysis). OUTLINE: This is a dose-escalation study. Patients are assigned to 1 of 3 cohorts. COHORT I: Patients receive elimusertib orally (PO) twice daily (BID) on days 1 and 2 and irinotecan intravenously (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 computed tomography (CT) and/or magnetic resonance imaging (MRI) throughout the study, tumor biopsy at screening and on study, and collection of blood samples at screening. COHORT II: Patients receive elimusertib PO once daily (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: Patients 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. After completion of study treatment, patients are followed every 2 months for up to 6 months.

Conditions

Interventions

TypeNameDescription
PROCEDUREBiopsyUndergo tumor biopsy
PROCEDUREBiospecimen CollectionUndergo collection of blood samples
PROCEDUREComputed TomographyUndergo CT
DRUGElimusertibGiven PO
DRUGIrinotecan HydrochlorideGiven IV
PROCEDUREMagnetic Resonance ImagingUndergo MRI
DRUGTopotecan HydrochlorideGiven IV

Timeline

Start date
2021-10-20
Primary completion
2025-02-15
Completion
2026-03-04
First posted
2020-08-17
Last updated
2025-03-06

Locations

23 sites across 1 country: United States

Regulatory

Source: ClinicalTrials.gov record NCT04514497. Inclusion in this directory is not an endorsement.