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

NCT04052555 | Active Not Recruiting Phase 1 FDA Drug

• 4 other identifiers: NCI-2019-0518710291UM1CA186686UM1CA186709
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 14

Brief 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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to 4 weeks post treatment

Secondary Outcomes (7)

• Incidence of adverse events (AEs)

  Up to 3 years

• Time to progression

  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)

  From study registration until the tumor recurs or the patient dies, whichever comes first, assessed up to 3 years

• Distant DFS

  From study registration until distant disease recurs or the patient dies, whichever comes first, assessed up to 3 years

• Overall survival

  From study registration until death due to any cause, assessed up to 3 years

Study Arms (1)

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.

Drug: Berzosertib; Procedure: Biospecimen Collection; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Radiation: Radiation Therapy

Interventions

Berzosertib DRUG

Given IV

Also known as: 2-Pyrazinamine, 3-(3-(4-((Methylamino)methyl)phenyl)-5-isoxazolyl)-5-(4-((1-methylethyl)sulfonyl)phenyl)-, M 6620, M6620, VX 970, VX-970, VX970

Treatment (berzosertib, radiation therapy)

Biospecimen Collection PROCEDURE

Correlative studies

Also known as: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

Treatment (berzosertib, radiation therapy)

Questionnaire Administration OTHER

Ancillary studies

Treatment (berzosertib, radiation therapy)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Treatment (berzosertib, radiation therapy)

Radiation Therapy RADIATION

Undergo RT

Also known as: Cancer Radiotherapy, Energy Type, ENERGY_TYPE, Irradiate, Irradiated, Irradiation, Radiation, Radiation Therapy, NOS, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation

Treatment (berzosertib, radiation therapy)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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)

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (14)

Mayo Clinic Hospital in Arizona

Phoenix, Arizona, 85054, United States

Location

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

NYP/Weill Cornell Medical Center

New York, New York, 10065, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, 15232, United States

Location

University of Texas Medical Branch

Galveston, Texas, 77555-0565, United States

Location

Farmington Health Center

Farmington, Utah, 84025, United States

Location

University of Utah Sugarhouse Health Center

Salt Lake City, Utah, 84106, United States

Location

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, 84112, United States

Location

University of Wisconsin Carbone Cancer Center - University Hospital

Madison, Wisconsin, 53792, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Triple Negative Breast Neoplasms

Interventions

berzosertib; Specimen Handling; Radiotherapy; Radiation

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Therapeutics; Physical Phenomena

Study Officials

• Robert W Mutter

  Dana-Farber - Harvard Cancer Center LAO

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 8, 2019
• First Posted: August 12, 2019
• Study Start: September 24, 2020
• Primary Completion (Estimated): February 24, 2027
• Study Completion (Estimated): February 24, 2027
• Last Updated: May 13, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share

Locations

US (14)