This phase Ib trials studies the side effects and how well talimogene laherparepvec works when given together with chemotherapy or endocrine therapy in treating patients with breast cancer that does not express the human epidermal growth factor receptor 2 (HER2) protein and has spread to other places in the body (metastatic), cannot be removed by surgery (unresectable), or has come back (recurrent). Biological therapies, such as talimogene laherparepvec, use substances made from living organisms that may attack specific tumor cells and stop them from growing or kill them. Chemotherapy drugs, such as nab-paclitaxel, gemcitabine, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Estrogen can cause the growth of breast cancer cells. Drugs used as endocrine therapy, such as letrozole, anastrozole, exemestane, tamoxifen or fulvestrant, may lessen the amount of estrogen made by the body or may may stop the growth of tumor cells by blocking estrogen from connecting to the cancer cells. Giving talimogene laherparepvec with chemotherapy or endocrine therapy may work better in treating patients with HER2-negative breast cancer.
PRIMARY OBJECTIVES: I. To evaluate the safety and tolerability of intra-lesional talimogene laherparepvec injections in combination with chemotherapy or endocrine therapy in patients with metastatic, unresectable, or locoregionally recurrent HER2-negative breast cancer who have injectable sites of disease. SECONDARY OBJECTIVES: To evaluate the efficacy of talimogene laherparepvec in combination with chemotherapy or endocrine therapy in the study population OUTLINE: Patients are assigned to 1 of 2 cohorts. COHORT I (CHEMOTHERAPY): Patients receive talimogene laherparepvec intra-tumorally (IT) on day 1 of cycle 1, on days 1 and 15 of cycle 2, on day 8 of cycle 3, then on day 1 of subsequent cycles. Patients also receive paclitaxel or nab-paclitaxel intravenously (IV) over 60 minutes on days 1, 8, and possibly 15, or gemcitabine IV over 30-60 minutes and carboplatin IV over 30-60 minutes on days 1 and 8. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. COHORT II (ENDOCRINE THERAPY): Patients receive talimogene laherparepvec IT every 2 weeks for the first 10 weeks and then every 3 weeks thereafter. Patients also receive letrozole orally (PO), anastrazole PO, exemestane PO, tamoxifen PO on days 1-28 or fulvestrant intramuscularly (IM) every 2 weeks for 3 doses then every 4 weeks for the subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 30 days.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
20
Given PO
Given PO
Given IM
Given PO
Given IV
Given IT
Given PO
Given IV
Given IV
Given IV
University of California, San Francisco
San Francisco, California, United States
Number of patients with treatment-related toxicities by maximum observed grade
Treatment-related toxicities will be assessed according to NCI CTCAE v4.03, for all patients who receive at least one dose of study treatment. The distribution for the maximum observed grade for each adverse event will be tabulated and reported with 95% confidence interval
Time frame: Up to 2.5 years
Maximum tolerated volume
The maximum tolerated volume will be the highest volume (up to 4mL) that results in \<=1 dose limiting toxicity (DLT) in 6 treated patients for the chemotherapy group. At least 15 patients will be treated in the chemotherapy cohort and at least 6 patients will be treated in the endocrine therapy cohort.
Time frame: Up to 2.5 years
Overall response rate (ORR)
The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence per Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1. Patients with complete response (CR) or partial response (PR) will be counted as having an objective response
Time frame: Up to 2.5 years
Response duration
Defined as the time from initial response to the first documented tumor progression.
Time frame: Up to 2.5 years
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