Elimusertib for the Treatment of Relapsed or Refractory Solid Tumors
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|ClinicalTrials.gov Identifier: NCT05071209|
Recruitment Status : Recruiting
First Posted : October 8, 2021
Last Update Posted : May 5, 2022
|Condition or disease||Intervention/treatment||Phase|
|Recurrent Alveolar Rhabdomyosarcoma Recurrent Ewing Sarcoma Recurrent Lymphoma Recurrent Malignant Solid Neoplasm Refractory Alveolar Rhabdomyosarcoma Refractory Ewing Sarcoma Refractory Lymphoma Refractory Malignant Solid Neoplasm||Drug: Elimusertib||Phase 1 Phase 2|
I. To estimate the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of BAY 1895344 (elimusertib) administered as an oral tablet, twice per day for 3 days on and 4 days off to patients < 18 years of age with recurrent or refractory Ewing sarcoma, PAX3-FOXO1 alveolar rhabdomyosarcoma, and non-central nervous system (CNS) solid tumors or lymphoma with specific deleterious deoxyribonucleic acid (DNA) damage response (DDR) pathway alterations. (Phase 1 Dose Escalation) II. To define the antitumor activity of BAY 1895344 (elimusertib) in pediatric patients and young adults with recurrent or refractory Ewing sarcoma. (Phase 2) III. To define the antitumor activity of BAY 1895344 (elimusertib) in pediatric patients and young adults with recurrent or refractory PAX3-FOXO1 fusion positive alveolar rhabdomyosarcoma. (Phase 2) IV. To define and describe the toxicities of BAY 1895344 (elimusertib) administered on this schedule. (Phase 1)
I. To characterize the pharmacokinetics of BAY 1895344 (elimusertib) in children and adolescents with recurrent or refractory cancer.
II. To assess the biologic activity of BAY 1895344 (elimusertib) by immunohistochemical assessments of phosphorylated (p)ATR, pH2AX, and pKAP1 in paired tissue samples before and after treatment with BAY 1895344 (elimusertib).
III. To assess whether the activity of BAY 1895344 (elimusertib) is influenced by alanine aminotransferase (ALT), as well as tumor tissue expression of ATM, PGBD5, and/or R-loops.
IV. To assess whether the activity of BAY 1895344 (elimusertib) is associated with tumor mutational processes, as measured by whole genome tumor tissue sequencing.
V. To preliminary determine the anti-tumor activity of BAY 1895344 (elimusertib) in children < 18 years of age within the confines of a phase 1 study (Part A).
VI. To assess the antitumor activity of BAY 1895344 (elimusertib) in pediatric patients with non-CNS solid tumors or lymphomas with specific deleterious alterations in DDR pathway genes. (Phase 2)
OUTLINE: This is a phase I, dose-escalation study followed by a phase II dose escalation study.
Patients receive elimusertib orally (PO) twice daily (BID) on days 1-3, 8-10, 15-17, and 22-24. Treatment repeats every 28 days for 26 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 12 months, every 6 months for 24 months, and then annually for up to 60 months.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||23 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1/ 2 Study of BAY 1895344 (Elimusertib, NSC#810486) in Pediatric Patients With Relapsed or Refractory Solid Tumors|
|Actual Study Start Date :||December 3, 2021|
|Estimated Primary Completion Date :||June 30, 2024|
|Estimated Study Completion Date :||June 30, 2024|
Experimental: Treatment (elimusertib)
Patients receive elimusertib PO BID on days 1-3, 8-10, 15-17, and 22-24. Treatment repeats every 28 days for 26 cycles in the absence of disease progression or unacceptable toxicity.
- Maximum tolerated dose [ Time Frame: Up to 28 days (cycle 1) ]
- Response rate (Phase2) [ Time Frame: Up to 60 months ]The response rate will be estimated by the uniform minimum variance unbiased estimate with one-sided p-value and confidence interval. Each disease cohort will be separately analyzed without adjusting for multiple hypothesis tests.
- Incidence of adverse events [ Time Frame: Up to 60 months ]Toxicities for patients will be described separately.
- Pharmacokinetic (PK) parameters [ Time Frame: Up to 60 months ]A descriptive analysis of PK parameters of BAY 1895344 (elimusertib) will be performed to define systemic exposure, drug clearance, and other pharmacokinetic parameters. The PK parameters will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit). All these analyses will be descriptive and exploratory and hypotheses generating in nature.
- Analysis of biomarkers [ Time Frame: Up to 60 months ]A descriptive analysis of biomarkers will assess associations with disease response. The parameters will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit). All these analyses will be descriptive and exploratory and hypotheses generating in nature.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05071209
|Principal Investigator:||Michael V Ortiz||Pediatric Early Phase Clinical Trial Network|