What side effects are associated with this type of intervention?

Common treatments for breast cancer that inhibit enzymes needed for cell growth, such as kinase inhibitors, often have side effects including fatigue, nausea, increased liver function tests, and gastrointestinal issues. Radiation therapy, which is frequently combined with these inhibitors, can cause skin irritation, fatigue, and localized pain. Specific agents like Berzosertib may also lead to more targeted side effects such as anemia and decreased neutrophil counts. Overall, while these treatments can be effective, they require careful management of their side effects.

What prior FDA approvals exist?

FDA-approved treatments for breast cancer that target enzymes needed for cell growth include kinase inhibitors like palbociclib, ribociclib, and abemaciclib, which inhibit cyclin-dependent kinases 4 and 6 (CDK4/6). These drugs are used in combination with hormone therapy for hormone receptor-positive, HER2-negative breast cancer. Additionally, PARP inhibitors such as olaparib and talazoparib are approved for patients with BRCA-mutated, HER2-negative breast cancer, as they inhibit the enzyme poly (ADP-ribose) polymerase, which is involved in DNA repair. These treatments share a similar approach to Berzosertib by targeting specific enzymes crucial for cancer cell proliferation and survival.

What other types of research exist?

Promising novel alternatives to Berzosertib for breast cancer patients include: 1) Trastuzumab deruxtecan, an antibody-drug conjugate targeting HER2-positive breast cancer. 2) Pyrotinib, a pan-HER receptor tyrosine kinase inhibitor effective in HER2-mutant breast cancer. 3) Pembrolizumab, an immune checkpoint inhibitor showing efficacy in triple-negative breast cancer. 4) Fulvestrant plus everolimus, a combination therapy for hormone-receptor positive, HER2-negative breast cancer.

← Back to Search

Berzosertib + Radiation for Triple-Negative Breast Cancer

Phase 1

Waitlist Available

Led By Robert W Mutter

Research Sponsored by National Cancer Institute (NCI)

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

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.

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

Must not have

Active systemic lupus, scleroderma, or dermatomyositis with a CPK level above normal

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

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 3 years

Awards & highlights

No Placebo-Only Group

Summary

This trial studies the best dose of berzosertib combined with radiation therapy for treating certain types of breast cancer. Berzosertib helps stop cancer cell growth by blocking important enzymes, while radiation kills the cancer cells. This combination may work better than radiation alone.

Who is the study for?

Adults over 18 with certain types of breast cancer (triple-negative or hormone receptor-positive, HER2-negative) that didn't respond to chemotherapy can join. They must have completed surgery and possibly postoperative chemo recently, be in good health otherwise, and agree to use contraception. People with recent chemo, prior radiation in the same area, uncontrolled illnesses, or known hypersensitivity to similar drugs are excluded.

What is being tested?

The trial is testing Berzosertib combined with standard radiation therapy against breast cancer that resisted chemotherapy. It aims to find the best dose of Berzosertib which blocks enzymes needed for cell growth and may enhance the effectiveness of radiation therapy.

What are the potential side effects?

Potential side effects include reactions related to DNA repair inhibition which could affect cell growth leading to fatigue, digestive issues or blood disorders. Specific side effects from combining Berzosertib with radiation aren't fully known but will be monitored closely.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

I had breast surgery with clear margins, or surgery for recurrent breast cancer with some untreated areas allowed.

Select...

My kidney function is normal or only slightly impaired.

Select...

I can take care of myself but might not be able to do heavy physical work.

Select...

My surgical wound has fully healed without any infection.

Select...

I am 18 years old or older.

Select...

I had hepatitis C but am now cured, or I am being treated with no detectable virus.

Select...

I am getting radiation therapy for breast cancer, including the chest wall and nearby lymph nodes, on one side only.

Select...

My hepatitis B virus is under control with treatment.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I have lupus, scleroderma, or dermatomyositis with high CPK levels.

Select...

I am not taking any strong medication that affects how drugs are processed in my body.

Select...

I do not have any serious ongoing illnesses that are not under control.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 3 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 3 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 3 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Recommended phase II dose of berzosertib

Secondary study objectives

Alterations in deoxyribonucleic acid damage response and repair genes

Change in patient-related outcomes (PRO)

Disease-free survival (DFS)

+4 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Treatment (berzosertib, radiation therapy)Experimental Treatment5 Interventions

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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Berzosertib

2021

Completed Phase 2

~80

Radiation Therapy

2017

Completed Phase 3

~7250

Biospecimen Collection

2004

Completed Phase 3

~2020

0 / 11Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Breast cancer treatments often target specific mechanisms that drive cancer cell growth and proliferation. For instance, Berzosertib inhibits enzymes essential for cell growth, thereby preventing tumor cells from multiplying. Similarly, hormone therapies like aromatase inhibitors block the production of estrogen, which can fuel the growth of hormone receptor-positive breast cancers. Targeted therapies, such as HER2 inhibitors, block the HER2 protein that promotes the growth of cancer cells. These treatments are crucial for breast cancer patients as they offer more personalized and effective options, potentially leading to better outcomes and fewer side effects compared to traditional chemotherapy.

Pharmacokinetics, clinical indications, and resistance mechanisms in molecular targeted therapies in cancer.New drugs for breast cancer.Endocrine therapy for early breast cancer.