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
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.
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 germline and somatic 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 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 assess for germline DNA repair alterations and correlate with severe provider and
patient-reported toxicity.
III. To explore dose-volume parameters associated with acute and late toxicity provider and
patient-reported toxicity following berzosertib administration concurrent with RT.
IV. 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.
V. To evaluate pre-treatment and post-treatment differential abundance of peripheral blood
immune cell populations identified by cytometry by time-of flight (CyTOF).
VI. 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.
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 also undergo
RT 5 days a week for 5-6 weeks depending on the type of surgery undergone.
After completion of study treatment, patients are followed up weekly for 4 weeks, at 12
months, then yearly for up to 3 years.
Details
Condition
Bilateral Breast Carcinoma, HER2-Negative Breast Carcinoma, Localized Breast Carcinoma, Recurrent Breast Carcinoma, Triple-Negative Breast Carcinoma
If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.
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