Locally Recurrent/Metastatic Triple Negative Breast Cancer
Conditions
Keywords
Treated with Concurrent Cisplatin, Treated with Radiation Therapy, Homologous Recombination Repair Status, Biomarker of Response, 15-032, Patients
Brief 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.
Interventions
RADIATIONexternal 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.
DRUGcisplatin
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.
PROCEDUREBiopsy 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.
Sponsors
Memorial Sloan Kettering Cancer Center
Cedars-Sinai Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response (RECIST 1.1 vs. PET Response Criteria (PRC) as Measurement Tools for Treatment Response) | 2 years from baseline | RECIST 1.1 as measurement tools for treatment response. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORSimon Powell, MD,PhD
Memorial Sloan Kettering Cancer Center
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Concurrent Cisplatin & Radiation Therapy 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.
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.
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. | 49 |
| Total | 49 |
Baseline characteristics
| Characteristic | Concurrent Cisplatin & Radiation Therapy |
|---|---|
| Age, Continuous | 54 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 44 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants |
| Race (NIH/OMB) Black or African American | 14 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Race (NIH/OMB) White | 27 Participants |
| Region of Enrollment United States | 49 Participants |
| Sex: Female, Male Female | 48 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 40 / 49 |
| other Total, other adverse events | 45 / 49 |
| serious Total, serious adverse events | 12 / 49 |
Outcome results
Primary
Response (RECIST 1.1 vs. PET Response Criteria (PRC) as Measurement Tools for Treatment Response)
RECIST 1.1 as measurement tools for treatment response.
Time frame: 2 years
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Concurrent Cisplatin & Radiation Therapy | Response (RECIST 1.1 vs. PET Response Criteria (PRC) as Measurement Tools for Treatment Response) | Partial Response | 2 Participants |
| Concurrent Cisplatin & Radiation Therapy | Response (RECIST 1.1 vs. PET Response Criteria (PRC) as Measurement Tools for Treatment Response) | Progression of Disease | 25 Participants |
| Concurrent Cisplatin & Radiation Therapy | Response (RECIST 1.1 vs. PET Response Criteria (PRC) as Measurement Tools for Treatment Response) | Not Entered | 22 Participants |