Phase 2
Completed N=15
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 · Anatomic Stage II Breast Cancer AJCC v8
Source: ClinicalTrials.gov NCT03774472 ↗
Enrolled (actual)
15
Serious AEs
0.0%
Results posted
Feb 2025
Primary outcomePrimary: Incidence of Adverse Events (Phase I) — 3; 3; 6 Participants
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Incidence of Adverse Events (Phase I) |
3; 3; 6 | — |
| SECONDARY Recommended Phase II Dose for HCQ |
800 | — |
| SECONDARY Clinical Benefit Rate at 8 Weeks |
100; 66.6; 100 | — |
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 = 28 days prior to first study treatment)
- Absolute neutrophil count (ANC) >= 1500 cells/ul
- Platelet count >= 100,000/ul
- Serum creatinine concentration = 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
Data sourced from ClinicalTrials.gov (NCT03774472). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.