NCT02648477

Pembrolizumab and Doxorubicin Hydrochloride or Anti-Estrogen Therapy in Treating Patients With Triple-Negative or Hormone Receptor-Positive Metastatic Breast Cancer

MK-3475 (Pembrolizumab) in Combination With an Anthracycline or Anti-estrogen Therapy in Patients With Triple Negative and Hormone Receptor Positive (HR+ HER2-) Metastatic Breast Cancer

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (actual)
• Sponsor: City of Hope Medical Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase II trial studies how well pembrolizumab and doxorubicin hydrochloride works compared to pembrolizumab with anti-estrogen therapy (anastrozole, letrozole, or exemestane) in treating patients with triple-negative or hormone-receptor positive breast cancer that has spread from the primary site (place where it started) to other places in the body. Pembrolizumab is an antibody drug that blocks a molecule called programmed death (PD)-1. PD-1 is a molecule that shuts down the body's immune responses and prevents the immune system from attacking the cancer. Doxorubicin hydrochloride is a drug used in chemotherapy that works to stop the growth of tumor cells by stopping them from dividing and by causing them to die. Anti-estrogen therapy, including anastrozole, letrozole, and exemestane, lowers estrogen levels in the body, which may help treat cancer that is hormone receptor-positive. Giving pembrolizumab together with standard treatment of either doxorubicin hydrochloride (triple-negative cancer) or anti-estrogen therapy (hormone receptor-positive cancer) may be an effective treatment for these types of breast cancer.

Detailed description

PRIMARY OBJECTIVES: I. To evaluate efficacy (overall response rate) of MK-3475 (pembrolizumab) and doxorubicin (doxorubicin hydrochloride) in patients with stage IV triple negative breast cancer. II. To evaluate efficacy (overall response rate) of MK-3475 and an oral aromatase inhibitor in patients with stage IV hormone receptor positive (HR+) human epidermal growth factor receptor 2 negative (HER2-) breast cancer. SECONDARY OBJECTIVES: I. To assess clinical benefit rate (lack of progression for \> 24 weeks), duration of response, time-to-treatment failure, progression-free survival, and overall survival in triple negative (TN) stage IV breast cancer patients based primarily on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and immune-related (ir)RECIST. II. To assess feasibility and toxicity. III. To assess clinical benefit rate (lack of progression for \> 24 weeks), duration of response, time-to-treatment failure, progression-free survival, and overall survival in patients with stage IV HR+ breast cancer based primarily on RECIST 1.1, and irRECIST. IV. To assess feasibility and toxicities. TERTIARY OBJECTIVES: I. To procure serial tumor (primary and metastatic) and blood (cellular and serum/plasma) samples and analyze them to better our understanding of cellular and humoral immune response correlates and predictors of clinical benefits, leading to optimized selection of target populations in future phase II and subsequent phase III randomized prospective trials. OUTLINE: Patients are assigned to 1 of 2 treatment arms. COHORT 1 (TRIPLE-NEGATIVE): Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1 and doxorubicin hydrochloride IV on day 1. Treatment repeats every 3 weeks for 6 courses, and then continues for up to 24 months with pembrolizumab alone in the absence of disease progression or unacceptable toxicity. COHORT 2 (HORMONE/HER2+): Patients receive pembrolizumab IV over 30 minutes on day 1 and an aromatase inhibitor (exemestane, anastrozole, or letrozole) orally (PO) once daily (QD) on days 1-21. Treatment repeats every 3 weeks for 24 months in the absence of disease progression or unacceptable toxicity. In both arms, patients who stop pembrolizumab with stable disease or better may receive additional pembrolizumab therapy for up to 1 year if they progress after stopping study treatment. After completion of study treatment, patients are followed up for 30 days after the end of treatment and then every 8-12 weeks thereafter.

Conditions

• Estrogen Receptor Negative
• Estrogen Receptor Positive
• HER2/Neu Negative
• Progesterone Receptor Negative
• Progesterone Receptor Positive
• Stage IV Breast Cancer
• Triple-Negative Breast Carcinoma

Interventions

Type	Name	Description
DRUG	Anastrozole	Given PO
DRUG	Doxorubicin Hydrochloride	Given IV
DRUG	Exemestane	Given PO
OTHER	Laboratory Biomarker Analysis	Correlative studies
DRUG	Letrozole	Given PO
BIOLOGICAL	Pembrolizumab	Given IV

Timeline

• Start date: 2016-03-28
• Primary completion: 2022-04-01
• Completion: 2023-12-30
• First posted: 2016-01-07
• Last updated: 2024-03-19
• Results posted: 2023-04-19

Locations

6 sites across 1 country: United States