Bilateral Breast CarcinomaPhase 1NCT04052555
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 1 study testing Berzosertib, Biospecimen Collection and Quality-of-Life Assessment in people with Bilateral Breast Carcinoma and HER2-Negative Breast Carcinoma, run by National Cancer Institute (NCI) at 14 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Bilateral Breast Carcinoma, HER2-Negative Breast Carcinoma, Localized Breast Carcinoma
- What is being tested?
- Berzosertib, Biospecimen Collection and Quality-of-Life Assessment
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 14 sitesUnited States
- Study dates
- 24 Sep 2020to 24 Feb 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males or females age >= 18 years. Note: Because no dosing or adverse event data are currently available on the use of berzosertib in combination with radiation therapy in patients < 18 years of age, children are excluded from this study, but will be eligible for future pediatric trials
- Patient with non-metastatic, histologically confirmed primary estrogen receptor (ER) =< 10%, progesterone receptor (PR) =< 10%, and HER2-negative breast cancer (triple negative breast cancer [TNBC]) either using the baseline biopsy specimen or the post-neoadjuvant chemotherapy (NAC) residual surgical specimen and RCB2 or RCB3, as defined by Symmans et al., 2007, and received neoadjuvant anthracycline and/or taxane-based chemotherapy OR Patient has non-metastatic, histologically confirmed primary ER > 10% and/or PR > 10%, HER2-negative breast cancer with RCB3 and received neoadjuvant anthracycline and/or taxane-based chemotherapy OR Patient has locoregionally recurrent TNBC or ER >10% and/or PR >10%, HER2-negative breast cancer.
- Note: Results from any Clinical Laboratory Improvement Act (CLIA)-certified lab are acceptable for the purpose of determining study eligibility.
- Note: For patients with primary breast cancer, there is no minimum number of neoadjuvant cycles required provided the patient received an anthracycline or taxane preoperatively. Patients with locoregionally recurrent breast cancer are not required to have received preoperative chemotherapy
- Patient has undergone total mastectomy or wide local excision with axillary staging, and the margins of the resected wide local excision or mastectomy specimens are free of invasive tumor and ductal carcinoma in situ (DCIS) or patient has undergone axillary surgery for regionally recurrent breast cancer. Unresected axillary level III, internal mammary, and supraclavicular nodal disease is permitted.
- Note: For patients who have undergone mastectomy, immediate reconstruction is allowed
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- Patients must have completed their final breast surgery, including re-excision of margins for invasive cancer and DCIS, within 90 but not fewer than 21 days prior to registration unless patient received postoperative chemotherapy in which case patients must have completed their adjuvant chemotherapy within 90 days but not fewer than 28 days prior to registration
- The patient must have recovered from surgery with the incision completely healed and no signs of infection prior to registration
- Patients must be proceeding with breast/chest wall and regional nodal irradiation including internal mammary node treatment. For patients with bilateral breast cancer, RT must be indicated and administered only to one side
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Willing to provide tissue and blood samples for correlative research
- Leukocytes >= institutional lower limit of normal (LLN)
- Absolute neutrophil count >= institutional LLN
- Platelets >= institutional LLN
- Total bilirubin =< 1.5 x institutional upper limit of normal (ULN)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x institutional ULN
- Creatinine =< 1.1 mg/dL OR
- Glomerular filtration rate (GFR) >= 45 mL/min/1.73 m^2 for patients with creatinine levels above 1.1 mg/dL
- Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
- Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
- Negative urine or serum pregnancy test for individuals of childbearing potential. Note: The effects of berzosertib on the developing human fetus are unknown. For this reason and because DNA-damage repair inhibitors as well as radiation used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation, and for 6 months after completion of berzosertib administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 6 months after completion of berzosertib administration
- Ability to understand and the willingness to sign a written informed consent document
Who cannot join
- Patients who have had chemotherapy within 4 weeks prior to entering the study
- Prior RT to the ipsilateral chest wall or ipsilateral breast or thorax. Individuals with prior RT to the contralateral breast or chest wall are eligible
- Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > grade 1) with the exception of alopecia and grade 1-2 taxane-induced neuropathy which will be permitted
- Patients who are receiving any other investigational agents or concomitant anti-neoplastic treatment, except endocrine therapies and bisphosphonates which are permitted without restriction even during protocol treatment. Postoperative chemotherapy is allowed but must be discontinued >28 days prior to registration
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to berzosertib
- Berzosertib is primarily metabolized by CYP3A4; therefore, concomitant administration with strong inhibitors of CYP3A4 (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir, indinavir, nelfinavir, and saquinavir) or inducers of CYP3A4 (e.g., rifampin, phenytoin, carbamazepine, phenobarbital, St. John's wort) should be avoided. Patients requiring any medications or substances that are strong inhibitors or inducers of CYP3A during the course of the study and for 14 days prior to enrollment are ineligible. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
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- Patients with uncontrolled intercurrent illness. This includes but is not limited to, ongoing uncontrolled serious infection requiring IV antibiotics at the time of registration, symptomatic congestive heart failure, unstable angina pectoris, symptomatic/uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Active systemic lupus, scleroderma, or dermatomyositis with a CPK level above normal
- Pregnant women are excluded from this study because berzosertib as a DNA damage repair inhibitor may have the potential for teratogenic or abortifacient. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with berzosertib, breastfeeding should be discontinued if the mother is treated with berzosertib
- Patients with known hereditary syndromes predisposing to radiosensitivity such as Li Fraumeni syndrome and ataxia telangiectasia are excluded from the study. Patients with mutations in breast cancer predisposition genes such as BRCA1, BRCA2, PALB2, CHEK2, and ATM are eligible
- Patients with a prior or concurrent malignancy, excluding non-melanoma skin cancers and non-invasive cancers whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen
Trial locations and contacts
14 sites in 1 country.
14 sites in 1 country
United States14 sites
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
Farmington Health Center
Farmington, Utah, 84025
University of Texas Medical Branch
Galveston, Texas, 77555-0565
Mayo Clinic in Florida
Jacksonville, Florida, 32224-9980
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, 53792
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08903
NYP/Weill Cornell Medical Center
New York, New York, 10065
Mayo Clinic Hospital in Arizona
Phoenix, Arizona, 85054
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817
University of Utah Sugarhouse Health Center
Salt Lake City, Utah, 84106
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112
Mayo Clinic in Arizona
Scottsdale, Arizona, 85259
About this study
Official title: 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
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.
Read the detailed description
PRIMARY OBJECTIVE:
- 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:
- 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.
- 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:
- 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).
- 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
- Being tested
- Berzosertib, Biospecimen Collection, Quality-of-Life Assessment, Questionnaire Administration, Radiation Therapy
- Medical subject headings
- Breast Neoplasms, Triple Negative Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BerzosertibDrug
Also called 2-Pyrazinamine, 3-(3-(4-((Methylamino)methyl)phenyl)-5-isoxazolyl)-5-(4-((1-methylethyl)sulfonyl)phenyl)-, M 6620, M6620, VX 970
Given IV
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection
Correlative studies
Quality-of-Life AssessmentOther
Also called Quality of Life Assessment
Ancillary studies
Questionnaire AdministrationOther
Ancillary studies
Radiation TherapyRadiation
Also called Cancer Radiotherapy, Energy Type, ENERGY_TYPE, Irradiate
Undergo RT
| Study group | Role | What they receive |
|---|---|---|
| Treatment (berzosertib, radiation therapy) | Experimental | Patients receive berzosertib IV over 60 minutes 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. Receives: Drug: Berzosertib; Procedure: Biospecimen Collection; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Radiation: Radiation Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recommended phase II dose of berzosertib
The maximum tolerated dose will be defined as the highest dose level with a dose-limiting toxicity rate closest to 0.25 and =< .33.
Measured: Up to 4 weeks post treatment
Secondary outcomes (7)
Incidence of adverse events (AEs)
Will be defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 and will be summarized descriptively for each dose level and the entire cohort. The number and severity of all AEs (overall and by dose-level) will be tabulated and summarized in this patient population. The grade 3+ AEs will also be described and summarized in a similar fashion.
Measured: Up to 3 years
Time to progression
Locoregional control will be split by each dose level and analyzed descriptively using Kaplan-Meier methodology.
Measured: From study registration until the tumor recurs in the ipsilateral breast, chest wall, axillary, supracavicular or internal mammary nodes (if before or synchronous with a systemic recurrence), assessed up to 3 years
Disease-free survival (DFS)
Will be split by each dose level and analyzed descriptively using Kaplan-Meier methodology.
Measured: From study registration until the tumor recurs or the patient dies, whichever comes first, assessed up to 3 years
Distant DFS
Will be split by each dose level and analyzed descriptively using Kaplan-Meier methodology.
Measured: From study registration until distant disease recurs or the patient dies, whichever comes first, assessed up to 3 years
Overall survival
Will be split by each dose level and analyzed descriptively using Kaplan-Meier methodology.
Measured: From study registration until death due to any cause, assessed up to 3 years
Change in patient-related outcomes (PRO)
Patient reported physical well-being, fatigue, skin toxicity (as measured by the PRO-CTCAE) and overall quality of life (as measured by the Breast-Q) will be summarized. The PRO-CTCAE data will be evaluated for data quality, to characterize baseline symptom status of patients on study and the change over time, to explore the development of symptomatic AEs and the change over time, and to explore the patient scores with other relevant clinical information, including clinician graded AEs. Changes in Breast-Q scores through time will be analyzed using graphical methods separately for each treatment level.
Measured: Baseline up to 3 years
Alterations in deoxyribonucleic acid damage response and repair genes
Will include effectors and regulators of homologous recombination (HR) and be correlated with HR deficiency with disease-free survival. Descriptive statistics (i.e., mean, median, standard deviation, and range) and graphical methods (i.e., boxplots, jitter plots) will be used to summarize and compare the relapses by different dose levels. The number of relapses between the HR-deficient versus (vs.) the HR-proficient patients will be compared using a Chi-square test or independence or Fisher's Exact test. DFS for the HR-deficient and HR-proficient patients will be analyzed using Kaplan-Meier methods.
Measured: Up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Aug 2019
- Study start24 Sep 2020
- Primary completion24 Feb 2027 (estimated)
- Study completion24 Feb 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Bilateral Breast CarcinomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 42 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Robert W Mutter, Principal investigator, Dana-Farber - Harvard Cancer Center LAO
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04052555
- Sponsor's protocol ID
- NCI-2019-05187
- Other IDs
- NCI-2019-05187, 10291, 10291, UM1CA186686, UM1CA186709
- Status last verified
- Jul 2026
- First submitted
- 8 Aug 2019
- Last updated
- 31 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.
Study at a glance
From the registry record, last updated by the sponsor on 31 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04052555
- Acronym / sponsor ID
- NCI-2019-05187
- Conditions
- Bilateral Breast Carcinoma, HER2-Negative Breast Carcinoma, Localized Breast Carcinoma, Recurrent Breast Carcinoma, Triple-Negative Breast Carcinoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 42 participants (estimated)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 24 Sep 2020 (actual)
- Primary completion
- 24 Feb 2027 (estimated)
- Study completion
- 24 Feb 2027 (estimated)
- First posted
- 12 Aug 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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:
- 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.
- 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:
- 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).
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (berzosertib, radiation therapy) | Experimental | Drug: Berzosertib, Procedure: Biospecimen Collection, Other: Quality-of-Life Assessment, Other: Questionnaire Administration, Radiation: Radiation TherapyPatients receive berzosertib IV over 60 minutes 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- Males or females age >= 18 years. Note: Because no dosing or adverse event data are currently available on the use of berzosertib in combination with radiation therapy in patients < 18 years of age, children are excluded from this study, but will be eligible for future pediatric trials
- Patient with non-metastatic, histologically confirmed primary estrogen receptor (ER) =< 10%, progesterone receptor (PR) =< 10%, and HER2-negative breast cancer (triple negative breast cancer [TNBC]) either using the baseline biopsy specimen or the post-neoadjuvant chemotherapy (NAC) residual surgical specimen and RCB2 or RCB3, as defined by Symmans et al., 2007, and received neoadjuvant anthracycline and/or taxane-based chemotherapy OR Patient has non-metastatic, histologically confirmed primary ER > 10% and/or PR > 10%, HER2-negative breast cancer with RCB3 and received neoadjuvant anthracycline and/or taxane-based chemotherapy OR Patient has locoregionally recurrent TNBC or ER >10% and/or PR >10%, HER2-negative breast cancer.
- Patient has undergone total mastectomy or wide local excision with axillary staging, and the margins of the resected wide local excision or mastectomy specimens are free of invasive tumor and ductal carcinoma in situ (DCIS) or patient has undergone axillary surgery for regionally recurrent breast cancer. Unresected axillary level III, internal mammary, and supraclavicular nodal disease is permitted.
- Patients must have completed their final breast surgery, including re-excision of margins for invasive cancer and DCIS, within 90 but not fewer than 21 days prior to registration unless patient received postoperative chemotherapy in which case patients must have completed their adjuvant chemotherapy within 90 days but not fewer than 28 days prior to registration
- The patient must have recovered from surgery with the incision completely healed and no signs of infection prior to registration
Key exclusion criteria (11 listed)
- Patients who have had chemotherapy within 4 weeks prior to entering the study
- Prior RT to the ipsilateral chest wall or ipsilateral breast or thorax. Individuals with prior RT to the contralateral breast or chest wall are eligible
- Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > grade 1) with the exception of alopecia and grade 1-2 taxane-induced neuropathy which will be permitted
- Patients who are receiving any other investigational agents or concomitant anti-neoplastic treatment, except endocrine therapies and bisphosphonates which are permitted without restriction even during protocol treatment. Postoperative chemotherapy is allowed but must be discontinued >28 days prior to registration
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to berzosertib
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BerzosertibAlso: 2-Pyrazinamine, 3-(3-(4-((Methylamino)methyl)phenyl)-5-isoxazolyl)-5-(4-((1-methylethyl)sulfonyl)phenyl)-, M 6620, M6620, VX 970Given IV | Drug | Treatment (berzosertib, radiation therapy) |
| Biospecimen CollectionAlso: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen CollectionCorrelative studies | Procedure or surgery | Treatment (berzosertib, radiation therapy) |
| Quality-of-Life AssessmentAlso: Quality of Life AssessmentAncillary studies | Other | Treatment (berzosertib, radiation therapy) |
| Questionnaire AdministrationAncillary studies | Other | Treatment (berzosertib, radiation therapy) |
| Radiation TherapyAlso: Cancer Radiotherapy, Energy Type, ENERGY_TYPE, IrradiateUndergo RT | Radiation | Treatment (berzosertib, radiation therapy) |
Primary outcome
Recommended phase II dose of berzosertib
Time frame: Up to 4 weeks post treatment
The maximum tolerated dose will be defined as the highest dose level with a dose-limiting toxicity rate closest to 0.25 and =< .33.
7 secondary outcomes
Incidence of adverse events (AEs)
Time frame: Up to 3 years
Time to progression
Time frame: From study registration until the tumor recurs in the ipsilateral breast, chest wall, axillary, supracavicular or internal mammary nodes (if before or synchronous with a systemic recurrence), assessed up to 3 years
Disease-free survival (DFS)
Time frame: From study registration until the tumor recurs or the patient dies, whichever comes first, assessed up to 3 years
Distant DFS
Time frame: From study registration until distant disease recurs or the patient dies, whichever comes first, assessed up to 3 years
Overall survival
Time frame: From study registration until death due to any cause, assessed up to 3 years
Change in patient-related outcomes (PRO)
Time frame: Baseline up to 3 years
Alterations in deoxyribonucleic acid damage response and repair genes
Time frame: Up to 3 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jul 2026.
- Individual participant dataSharing planned: Yes. NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Robert W Mutter principal investigator
Dana-Farber - Harvard Cancer Center LAO
14 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Berzosertib, Biospecimen Collection and Quality-of-Life Assessment in people with Bilateral Breast Carcinoma and HER2-Negative Breast Carcinoma, run by National Cancer Institute (NCI) at 14 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 23 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 31 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Recommended phase II dose of berzosertib (time frame: Up to 4 weeks post treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jul 2026.