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

NCT03774472 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: 2017-0071NCI-2018-01050
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

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; Anatomic Stage IIA Breast Cancer AJCC v8; Anatomic Stage IIB Breast Cancer AJCC v8; Anatomic Stage III Breast Cancer AJCC v8; Anatomic Stage IIIA Breast Cancer AJCC v8; Anatomic Stage IIIB Breast Cancer AJCC v8; Anatomic Stage IIIC Breast Cancer AJCC v8; Anatomic Stage IV Breast Cancer AJCC v8; Prognostic Stage I Breast Cancer AJCC v8; Prognostic Stage IA Breast Cancer AJCC v8; Prognostic Stage IB Breast Cancer AJCC v8; Prognostic Stage IIA Breast Cancer AJCC v8; Prognostic Stage IIB Breast Cancer AJCC v8; Prognostic Stage III Breast Cancer AJCC v8; Prognostic Stage IIIA Breast Cancer AJCC v8; Prognostic Stage IIIB Breast Cancer AJCC v8; Prognostic Stage IIIC Breast Cancer AJCC v8; Prognostic Stage IV Breast Cancer AJCC v8

Outcome Measures

Primary Outcomes (1)

• Incidence of Adverse Events (Phase I)

  Incidence of adverse events (Phase I) \[Time Frame: Up to 30 days post-treatment\] Assessed continuously using Common Terminology Criteria for Adverse Events version 4.03, with physical examination and laboratory assessments.

  Up to 5 years and 4 months

Secondary Outcomes (2)

• Recommended Phase II Dose for HCQ

  Up to 5 years and 4 months

• Clinical Benefit Rate at 8 Weeks

  Up to 5 years and 4 months

Study Arms (1)

Treatment (hydroxychloroquine, palbociclib, letrozole)

EXPERIMENTAL

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.

Drug: Hydroxychloroquine; Drug: Letrozole; Drug: Palbociclib

Interventions

Hydroxychloroquine DRUG

Given PO

Treatment (hydroxychloroquine, palbociclib, letrozole)

Letrozole DRUG

Given PO

Also known as: CGS 20267, Femara

Treatment (hydroxychloroquine, palbociclib, letrozole)

Palbociclib DRUG

Given PO

Also known as: 6-Acetyl-8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-8h-pyrido(2,3-d)pyrimidin-7-one, Ibrance, PD 0332991, PD 332991, PD 991, PD-0332991

Treatment (hydroxychloroquine, palbociclib, letrozole)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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%

You may not qualify if:

• 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

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Raghavendra AS, Kettner NM, Kwiatkowski D, Damodaran S, Wang Y, Ramirez D, Gombos DS, Hunt KK, Shen Y, Keyomarsi K, Tripathy D. Phase I trial of hydroxychloroquine to enhance palbociclib and letrozole efficacy in ER+/HER2- breast cancer. NPJ Breast Cancer. 2025 Jan 26;11(1):7. doi: 10.1038/s41523-025-00722-1.

  PMID: 39865083 DERIVED

Related Links

• MD Anderson Cancer Center Website

MeSH Terms

Interventions

Hydroxychloroquine; Letrozole; palbociclib

Intervention Hierarchy (Ancestors)

Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Debasish Tripathy
• Organization: M D Anderson Cancer Center

dtripathy@mdanderson.org

713-794-4385

Study Officials

• Debasish Tripathy

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 7, 2018
• First Posted: December 13, 2018
• Study Start: August 20, 2018
• Primary Completion: April 17, 2024
• Study Completion: April 17, 2024
• Last Updated: February 17, 2025
• Results First Posted: February 17, 2025

Record last verified: 2025-02

Locations

US (1)