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
Condition: Locally Recurrent/Metastatic Triple Negative Breast Cancer
MeSH terms: Breast Neoplasms; Triple Negative Breast Neoplasms; Recurrence
Intervention: external beam radiation therapy; cisplatin; Biopsy of Target Tumor
Intervention description: 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.; 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.; 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.
Intervention MeSH terms: Cisplatin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 49.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Treated with Concurrent Cisplatin; Treated with Radiation Therapy; Homologous Recombination Repair Status; Biomarker of Response; 15-032; Patients

Summary:

      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.
    

Eligibility criteria:

        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.