Hydroxychloroquine, Palbociclib, and Letrozole Before Surgery in Treating Patients With Estrogen Receptor Positive, HER2 Negative Breast Cancer

• Status: Recruiting
• Trial end date: 2024-12-31
• Target enrollment: 0
• Participant gender: Female

Summary

This phase I/II trial studies the side effects and best dose of hydroxychloroquine when given together with palbociclib and letrozole before surgery in treating patients with estrogen receptor positive, HER2 negative breast cancer. Hydroxychloroquine is a substance that decreases immune responses in the body. Palbociclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Estrogen can cause the growth of breast cancer cells. Drugs, such as letrozole, may lessen the amount of estrogen made by the body. Giving hydroxychloroquine, palbociclib, and letrozole before surgery may work better than palbociclib and letrozole in treating patients with breast cancer.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: M.D. Anderson Cancer Center
• Collaborator: National Cancer Institute (NCI)
• Treatments: Estrogens; Hydroxychloroquine; Letrozole; Palbociclib

Criteria

Inclusion Criteria:

• Signed written informed consent

• Diagnosis of estrogen positive breast cancer, estrogen receptor-positive and HER2-negative by American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) criteria

• Eastern Cooperative Oncology Group (ECOG) performance status 0-1

• Postmenopausal defined by: a. Age >= 55 years and 1 year or more of amenorrhea b. Age < 55 years and 1 year or more of amenorrhea with luteinizing hormone (LH) and/or follicle stimulating hormone (FSH) levels in the postmenopausal range c. Age < 55 with prior hysterectomy but intact ovaries with LH and/or FSH levels in the postmenopausal range d. Chemotherapy or medically induced ovarian suppression with 1 year or more of amenorrhea and with LH and/or FSH levels in the postmenopausal range e. Status after bilateral oophorectomy (>= 28 days prior to first study treatment)

• Absolute neutrophil count (ANC) >= 1500 cells/ul

• Platelet count >= 100,000/ul

• Serum creatinine concentration < 1.5 x upper limit of normal (ULN)

• Bilirubin level < 1.5 x ULN

• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 3 x ULN

• Alkaline phosphatase =< 2.5 ULN

• Metastatic cohorts (Phase I): Diagnosis of stage IV estrogen positive breast cancer, estrogen receptor-positive and HER2-negative by ASCO/CAP criteria

• Metastatic cohorts (Phase I): Must be a candidate for treatment with CDK4/6 inhibitor and hormonal therapy with an aromatase inhibitor as standard of care

• Metastatic cohorts (Phase I): No prior exposure to CDK 4/6 inhibitors

• Neoadjuvant cohorts (Phase II): Diagnosis of stage I-III estrogen positive breast cancer, estrogen receptor-positive and HER2-negative by ASCO/CAP criteria. If stage I, clinical tumor size must be >= 1.5 cm

• Neoadjuvant cohorts (Phase II): Baseline tumor Ki67 > 5%

• Neoadjuvant cohorts (Phase II): Surgical candidate and appropriate for pre-operative endocrine therapy

Exclusion Criteria:

• Prior exposure to CDK 4/6 inhibitor therapy

• History of retinal disease or active visual disturbances (normal baseline study-specified retinal exam required)

• Acute illness, including infections requiring medical therapy, known bleeding diathesis or need for anticoagulation

• Treatment with any of the following medications within 4 weeks before the baseline diagnostic biopsy is taken: a. Oral estrogens, including hormone replacement therapy (but prior depot estrogen use not allowed). b. Investigational agents (or 5 half-lives, whichever is longer)

• Required concomitant use of any drug that is a strong CYP3A inhibitor or inducer

• Psychological, familial, sociological or geographical conditions that do not permit compliance with the study protocol

• Life expectancy of less than 6 months

• Pregnancy, lactation or planning to be pregnant.

• Neo-adjuvant cohorts (Phase II): Prior therapy for breast cancer (medical, surgical or radiation therapy)

• Neo-adjuvant cohorts (Phase II): Clinical T4 disease

• Neo-adjuvant cohorts (Phase II): Inoperable or metastatic breast cancer based on standard evaluation