Homologous Recombination Repair Status as a Biomarker of Response in Locally Recurrent/Metastatic Triple Negative Breast Cancer Patients Treated With Concurrent Cisplatin and Radiation Therapy

A Phase II Trial of Homologous Recombination Repair Status as a Biomarker of Response in Locally Recurrent/Metastatic Triple Negative Breast Cancer Patients Treated With Concurrent Cisplatin and Radiation Therapy

The study is being done to find out if the results of a pre-treatment biopsy can predict response to cisplatin and radiation treatment for patients with metastatic or recurrent triple negative breast cancer.

Study Overview

• Status: Completed
• Conditions: Locally Recurrent/Metastatic Triple Negative Breast Cancer
• Intervention / Treatment: Radiation: external beam radiation therapy; Drug: cisplatin; Procedure: Biopsy of Target Tumor

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Basking Ridge, New Jersey, United States, 07920
      • Memorial Sloan Kettering at Basking Ridge
    • Middletown, New Jersey, United States, 07748
      • Memorial Sloan Kettering Monmouth
    • Montvale, New Jersey, United States, 07645
      • Memorial Sloan Kettering Bergen
  • New York
    • Commack, New York, United States, 11725
      • Memorial Sloan Kettering Cancer Center @ Suffolk
    • Harrison, New York, United States, 10604
      • Memorial Sloan Kettering Westchester
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • Uniondale, New York, United States, 11553
      • Memorial Sloan Kettering Nassau

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically-confirmed invasive triple negative breast cancer (ER <1%, PR <1%, her-2-neu 0-1+ by IHC or FISH-negative) or as determined by MD discretion
• Radiation to the recurrent or metastatic site is clinically indicated and would be considered standard care for palliation or for locoregional control
• Age ≥18 years
• Tumor to be irradiated is measurable by RECIST 1.1 or PRC
• Willingness to undergo tumor biopsy prior to initiation of treatment
• Life expectancy greater than 6 months
• ECOG performance status 0-2
• Any prior chemotherapy is allowed including prior treatment with platinum-containing chemotherapy
• Prior treatment with FDA-approved or investigational biologics or novel molecularly target therapies, including oral or IV formulations, are permitted.
• Patients must be off prior targeted therapy for at least 14 days prior to study biopsy.
• Use of an effective means of contraception in women of child-bearing potential
• Ability to comprehend and sign informed consent

• Adequate organ and marrow function within 14 days prior to study entry, defined as:

  • Absolute neutrophil count (ANC)>1000/mm3
  • Hemoglobin >9 gm/dl
  • Platelets >100,000/mm3
  • Serum creatinine <1.5 mg/dl OR creatinine clearance of ≥ 50 cc/min
  • SGOT/SGPT<2.5X institutional ULN (<5X ULN if known liver metastases)

Exclusion Criteria:

• Unmeasurable target tumor site by RECIST 1.1 or PRC (ex: lesions <2 cm on CT or MR scan, leptomeningeal disease, ascites, pleural/pericardial effusion, lymphangitis, non-FDG-avid skin lesions)
• Brain metastases requiring focal or whole brain radiation will be excluded, as these lesions cannot be biopsied and can have life expectancies <6 months.
• Inability to obtain a biopsy of the tumor as deemed by the study Interventional Radiologist
• Prior chemotherapy completed <7 days prior to planned study entry

• Prior RT is allowed and must have been completed more than 7 days before planned study entry.

  • Note: For re-irradiation cases, standard departmental guidelines should be followed so as to not exceed normal tissue
• Life expectancy less than 6 months
• Intercurrent illness or other major medical condition or comorbid condition that might affect study participation (uncontrolled renal, pulmonary or hepatic dysfunction or infection)
• Renal dysfunction for which cisplatin dose would be considered unsafe.
• Women on study must be neither pregnant nor nursing nor expected to become pregnant during therapy. For premenopausal women, negative pregnancy test within 14 days of RT is required.
• Concurrent active malignancy other than non-melanomatous skin cancer or carcinoma in-situ of the cervix, unless treatment for the previous cancer was completed >2 years prior to study entry and patient has remained disease-free.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Concurrent Cisplatin & Radiation Therapy

Radiation: external beam radiation therapy; Radiation therapy to the target tumor will be delivered with external beam radiation therapy. In metastatic cases where the intent is palliative, the dose of radiation will be 3750 cGy delivered in 15 daily fractions, 4-5 days a week. In locoregionally recurrent cases where the intent is to enhance locoregional control, the dose of radiation will be 5000 cGy delivered in 25 fractions, 4-5 days a week plus an optional 10-14 Gy boost to areas of gross tumor.; Drug: cisplatin; Cisplatin treatment should be initiated following study registration. The dose of cisplatin is established as 25 mg/m^2 ivpb once a week (+ 3 days) for 1-2 weeks prior to radiation. The length of one cycle of Cisplatin is 21 days.; Procedure: Biopsy of Target Tumor; Biopsy of the tumor to be irradiated will be performed. Fresh tissue specimens will be sent to the laboratory for performance of the MSK-HRR Assay.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response (RECIST 1.1 vs. PET Response Criteria (PRC) as Measurement Tools for Treatment Response)	RECIST 1.1 as measurement tools for treatment response.	2 years

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborators: Cedars-Sinai Medical Center
• Investigators: Principal Investigator: Simon Powell, MD,PhD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

Helpful Links

• Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): April 14, 2015
• Primary Completion (Actual): December 19, 2022
• Study Completion (Actual): December 19, 2022

Study Registration Dates

• First Submitted: April 14, 2015
• First Submitted That Met QC Criteria: April 20, 2015
• First Posted (Estimated): April 21, 2015

Study Record Updates

• Last Update Posted (Estimated): February 9, 2024
• Last Update Submitted That Met QC Criteria: February 5, 2024
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: Patients; Treated with Concurrent Cisplatin; Treated with Radiation Therapy; Homologous Recombination Repair Status; Biomarker of Response; 15-032
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Neoplasms; Neoplasms by Site; Disease Attributes; Breast Diseases; Breast Neoplasms; Recurrence; Triple Negative Breast Neoplasms; Antineoplastic Agents; Cisplatin
• Other Study ID Numbers: 15-032