NCT04052555

Testing the Addition of an Anti-cancer Drug, Berzosertib, to the Usual Treatment (Radiation Therapy) for Chemotherapy-Resistant Triple-Negative and Estrogen and/or Progesterone Receptor Positive, HER2 Negative Breast Cancer

A Phase 1b Study of Berzosertib in Combination With Radiation Therapy to Overcome Therapeutic Resistance in Chemotherapy Resistant Triple Negative and Estrogen and/or Progesterone Receptor Positive, HER2 Negative Breast Cancer

• Status: Active Not Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 42 (estimated)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase Ib trial studies the best dose of berzosertib when given together with the usual treatment (radiation therapy) in treating patients with triple negative or estrogen receptor and/or progesterone receptor positive, HER-2 negative breast cancer. Berzosertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high energy rays to kill tumor cells and shrink tumors. Giving M6620 and radiation therapy may kill tumor cells more effectively than radiation alone or shrink or stabilize breast cancer for longer than radiation therapy alone.

Detailed description

PRIMARY OBJECTIVE: I. To determine the recommended phase 2 dose of twice weekly berzosertib administered concurrently with conventionally fractionated radiation therapy (RT) to the breast/chest wall and regional nodes. SECONDARY OBJECTIVES: I. To describe the nature of toxicity that develops when an ATR inhibitor is administered concurrently with RT for breast cancer using provider assessments. II. To assess long-term locoregional control, disease-free survival, distant disease-free survival, and overall survival of patients treated with this approach. III. To explore symptomatic adverse events and tolerability of berzosertib being administered concurrently with RT using patient-reported outcomes (PROs). IV. To assess for alterations in deoxyribonucleic acid (DNA) damage response and repair genes, including effectors and regulators of homologous recombination (HR), in pre-chemotherapy biopsy specimens and post-chemotherapy surgical resection specimens using whole exome sequencing (WES) and ribonucleic acid (RNA) sequencing (RNAseq), and to correlate HR deficiency with disease-free survival. V. To identify somatic alterations in circulating cell-free DNA (cfDNA) at baseline, mid-treatment, end-of-treatment, and follow-up and to correlate cfDNA with disease-free survival. EXPLORATORY OBJECTIVES: I. To compare the baseline and post-treatment skin microbiome and make exploratory correlations with severe provider and patient-reported toxicity. II. To explore dose-volume parameters associated with acute and late provider and patient-reported toxicity following berzosertib administration concurrent with RT. III. To identify circulating tumor cell (CTC) positivity at baseline, mid-treatment, end-of-treatment, and follow-up and to correlate CTC positivity or the combination of CTC positivity and cfDNA with disease-free survival. IV. To evaluate pre-treatment and post-treatment differential abundance of peripheral blood immune cell populations identified by cytometry by time-of flight (CyTOF). V. To evaluate associations of the pre-treatment and post-treatment peripheral blood immune phenotype (as assessed by CyTOF) with disease-free survival, distant disease-free survival and overall survival. VI. To explore the USP21-ATR pathway and its association with epithelial to mesenchymal transition (EMT) in therapeutically resistant breast cancer specimens at pre-treatment and post-treatment timepoints using immunohistochemistry (IHC) and RNAseq. OUTLINE: This is a dose-escalation study of berzosertib. Patients receive berzosertib intravenously (IV) over 60 minutes twice weekly (BIW) for 5 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo RT 5 days a week for 5-6 weeks depending on the type of surgery undergone. Patients also undergo a collection of blood on study. After completion of study treatment, patients are followed up weekly for 4 weeks, at 12 months, then yearly for up to 3 years.

Conditions

• Bilateral Breast Carcinoma
• HER2-Negative Breast Carcinoma
• Localized Breast Carcinoma
• Recurrent Breast Carcinoma
• Triple-Negative Breast Carcinoma

Interventions

Type	Name	Description
DRUG	Berzosertib	Given IV
PROCEDURE	Biospecimen Collection	Correlative studies
OTHER	Quality-of-Life Assessment	Ancillary studies
OTHER	Questionnaire Administration	Ancillary studies
RADIATION	Radiation Therapy	Undergo RT

Timeline

• Start date: 2020-09-24
• Primary completion: 2027-02-24
• Completion: 2027-02-24
• First posted: 2019-08-12
• Last updated: 2026-04-13

Locations

14 sites across 1 country: United States

Regulatory

• FDA-regulated drug study