Hydroxychloroquine, Palbociclib, and Letrozole Before Surgery in Treating Patients With Estrogen Receptor Positive, HER2 Negative Breast Cancer
Anatomic Stage I Breast Cancer AJCC v8, Anatomic Stage IA Breast Cancer AJCC v8, Anatomic Stage IB Breast Cancer AJCC v8
About this trial
This is an interventional treatment trial for Anatomic Stage I Breast Cancer AJCC v8
Eligibility 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
Sites / Locations
- M D Anderson Cancer Center
Arms of the Study
Arm 1
Experimental
Treatment (hydroxychloroquine, palbociclib, letrozole)
PHASE I: Patients with advanced, metastatic (stage IV) breast cancer receive hydroxychloroquine PO QD, palbociclib PO QD, and letrozole PO QD on days 1-28. Cycles repeat every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity. PHASE II: Patients with early stage (stage I-III) breast cancer receive hydroxychloroquine PO QD on days 15-28 of cycle 1 and on days 1-28 of subsequent cycles. Patients also receive palbociclib PO QD, and letrozole PO QD on days 1-28, followed by standard of care surgery at week 5. If there is a proliferative benefit with CCCA by biopsy at 4 weeks, cycles may repeat every 28 days for up to 20-24 weeks in the absence of disease progression or unacceptable toxicity, followed by standard of care surgery during weeks 20-24.