This phase I trial studies the side effects and best dose of olaparib when given with hyperthermia in treating patients with breast cancer that has come back in the chest wall. Olaparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Hyperthermia treatment may kill or damage tumor cells by heating them to several degrees above normal body temperature. Giving olaparib and hyperthermia treatment may work better in treating patients with breast cancer that has come back in the chest well compared to standard of care.
PRIMARY OBJECTIVES: I. To determine the dose limiting toxicities and maximum tolerated dose of olaparib given in combination with chest wall hyperthermia in patients with locally advanced or metastatic breast cancer with chest wall recurrences who have wild-type BRCA status (patients with germline BRCA mutations are excluded from this study). SECONDARY OBJECTIVES: I. To determine the local progression free survival (in months) for patients with chest wall recurrences defined as time to progression of disease on chest wall with olaparib with hyperthermia. II. To determine the 1-year progression free survival (in months) for patients with chest wall recurrences treated with olaparib with hyperthermia. III. To determine the best local overall response rate of chest wall after the combination of hyperthermia and olaparib. IV. To determine the quality of life and pain scores before, during and after treatment as measured by the Edmonton Symptom Assessment System which includes a pain score and 8 other subjective measures of wellness for cancer patients (0 to 10). EXPLORATORY OBJECTIVES: I. To evaluate BRCA1/2 levels by immunohistochemistry and explore if hyperthermia induced BRCA1/2 expression. II. To evaluate HR (homologous recombination) competency by RAD51 foci and explore if hyperthermia induces homologous recombination in breast tissue. III. To explore deoxyribonucleic acid (DNA) damage as measured by gammaH2AX and comet assay in cells dissociated from biopsy tissues. OUTLINE: This is a dose-escalation study of olaparib. Patients receive olaparib orally (PO) twice daily (BID). Treatment continues for 4 weeks in the absence of disease progression and unacceptable toxicity. Beginning week 2, patients also undergo hyperthermia treatment over 1 hour twice weekly for 3 weeks in the absence of disease progression and unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 12 months.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
3
Given PO
Undergo hyperthermia treatment
Ancillary studies
Ancillary studies
Sidney Kimmel Cancer Center at Thomas Jefferson University
Philadelphia, Pennsylvania, United States
Incidence of adverse events
Will be continually assessed according to the National Cancer Institute Common Toxicity Criteria for Adverse Advents (CTCAE version \[v\]5.0).
Time frame: Up to 1 year post treatment
Local progression free-survival (PFS)
Will be reported as Kaplan-Meier survival curves with the median survival time with 95% confidence interval. Will be analyzed using log-rank test as well as Cox proportional hazard models.
Time frame: From first dose of olaparib to the date of the first documented disease progression or recurrence on the chest wall, assessed up to 1 year
PFS
Will be assessed using Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Will be reported as Kaplan-Meier survival curves with the median survival time with 95% confidence interval. Will be analyzed using log-rank test as well as Cox proportional hazard models.
Time frame: From first dose of olaparib to the date of the first documented disease progression or recurrence, or death due to any cause, whichever occurs first, assessed up to 1 year
Best local overall response rate (ORR)
Defined as the number of subjects with a best overall response (BOR) defined as a complete response (CR) or partial response (PR) divided by the number of enrolled subjects. The proportion of patients will be summarized together with the appropriate 95% confidence interval. The binary endpoint of ORR will be compared by test on proportions.
Time frame: Up to 1 year post treatment
Quality of life (QOL)
Defined by the Edmonton Symptom Assessment System (ESAS) using nine subjective patient measures of well-being including pain, tiredness, nausea, depression, anxiety, drowsiness, appetite, well-being, shortness of breath. These will be rated by the patients during each visit (visits 1-6) and the change in values will correlate to an improvement in quality of life (a positive change will correlate to an improvement and a negative change will correlate to a worsening of pain). The multinominal/ordinal endpoints in QOLs will be summarized in frequencies ad proportions and compared using trend test.
Time frame: Up to 1 year post treatment
Pain scores
Defined by the Edmonton Symptom Assessment System (ESAS) using nine subjective patient measures of well-being including pain, tiredness, nausea, depression, anxiety, drowsiness, appetite, well-being, shortness of breath. These will be rated by the patients during each visit (visits 1-6) and the change in values will correlate to an improvement in quality of life (a positive change will correlate to an improvement and a negative change will correlate to a worsening of pain).
Time frame: Up to 1 year post treatment
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