Trial Outcomes & Findings for Hydroxychloroquine, Palbociclib, and Letrozole Before Surgery in Treating Patients With Estrogen Receptor Positive, HER2 Negative Breast Cancer (NCT NCT03774472)

Last Updated: 2025-02-17

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

15 participants

Primary outcome timeframe

Up to 5 years and 4 months

Results posted on

2025-02-17

Participant Flow

Participant milestones

Participant milestones
Measure	HCQ at 400mg 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.	HCQ at 600mg 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.	HCQ at 800mg 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.
Overall Study STARTED	4	5	6
Overall Study COMPLETED	3	3	6
Overall Study NOT COMPLETED	1	2	0

Reasons for withdrawal

Reasons for withdrawal
Measure	HCQ at 400mg 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.	HCQ at 600mg 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.
Overall Study Physician Decision	1	0
Overall Study Progression prior to 4 weeks	0	1
Overall Study Withdrawal by Subject	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: Up to 5 years and 4 months

Outcome measures

Outcome measures
Measure	HCQ at 400 mg n=3 Participants 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.	HCQ at 600 mg n=3 Participants 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.	HCQ at 800 mg n=6 Participants 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.
Incidence of Adverse Events (Phase I)	3 Participants	3 Participants	6 Participants

SECONDARY outcome

Timeframe: Up to 5 years and 4 months

Phase I portion in the metastatic setting is to determine the safety of adding HCQ to continuous low dose palbociclib and letrozole and to determine the recommended phase II dose for HCQ for the subsequent Phase II study.

Outcome measures

Outcome measures
Measure	HCQ at 400 mg n=12 Participants 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.	HCQ at 600 mg 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.	HCQ at 800 mg 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.
Recommended Phase II Dose for HCQ	800 mg/day	—	—

SECONDARY outcome

Timeframe: Up to 5 years and 4 months

The secondary objective is to determine the response rate and clinical benefit rate at 8 weeks of the assigned HCQ dose plus continuous low dose palbociclib and letrozole.

Outcome measures

Outcome measures
Measure	HCQ at 400 mg n=3 Participants 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.	HCQ at 600 mg n=3 Participants 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.	HCQ at 800 mg n=6 Participants 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.
Clinical Benefit Rate at 8 Weeks	100 percentage of participants	66.6 percentage of participants	100 percentage of participants

Adverse Events

HCQ at 400mg

Serious events: 0 serious events

Other events: 4 other events

Deaths: 2 deaths

HCQ at 600mg

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

HCQ at 800mg

Serious events: 0 serious events

Other events: 6 other events

Deaths: 2 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	HCQ at 400mg n=4 participants at risk 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.	HCQ at 600mg n=4 participants at risk 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.	HCQ at 800mg n=6 participants at risk 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.
Blood and lymphatic system disorders Anemia	75.0% 3/4 • Number of events 3 • Up to 5 years and 4 months	25.0% 1/4 • Number of events 1 • Up to 5 years and 4 months	50.0% 3/6 • Number of events 3 • Up to 5 years and 4 months
Eye disorders Blurred Vision	0.00% 0/4 • Up to 5 years and 4 months	25.0% 1/4 • Number of events 1 • Up to 5 years and 4 months	0.00% 0/6 • Up to 5 years and 4 months
General disorders Fatigue	0.00% 0/4 • Up to 5 years and 4 months	25.0% 1/4 • Number of events 1 • Up to 5 years and 4 months	50.0% 3/6 • Number of events 3 • Up to 5 years and 4 months
Gastrointestinal disorders Diarrhea	0.00% 0/4 • Up to 5 years and 4 months	25.0% 1/4 • Number of events 1 • Up to 5 years and 4 months	66.7% 4/6 • Number of events 4 • Up to 5 years and 4 months
Gastrointestinal disorders Nausea	25.0% 1/4 • Number of events 1 • Up to 5 years and 4 months	50.0% 2/4 • Number of events 2 • Up to 5 years and 4 months	16.7% 1/6 • Number of events 1 • Up to 5 years and 4 months
Gastrointestinal disorders Mucositis oral	25.0% 1/4 • Number of events 1 • Up to 5 years and 4 months	0.00% 0/4 • Up to 5 years and 4 months	0.00% 0/6 • Up to 5 years and 4 months
Gastrointestinal disorders Constipation	0.00% 0/4 • Up to 5 years and 4 months	25.0% 1/4 • Number of events 1 • Up to 5 years and 4 months	0.00% 0/6 • Up to 5 years and 4 months
Gastrointestinal disorders Gastroesophageal reflux disease	0.00% 0/4 • Up to 5 years and 4 months	25.0% 1/4 • Number of events 1 • Up to 5 years and 4 months	0.00% 0/6 • Up to 5 years and 4 months
Blood and lymphatic system disorders Neutrophil count decreased	50.0% 2/4 • Number of events 2 • Up to 5 years and 4 months	50.0% 2/4 • Number of events 2 • Up to 5 years and 4 months	83.3% 5/6 • Number of events 5 • Up to 5 years and 4 months
Blood and lymphatic system disorders Lymphocyte count decreased	25.0% 1/4 • Number of events 1 • Up to 5 years and 4 months	25.0% 1/4 • Number of events 1 • Up to 5 years and 4 months	16.7% 1/6 • Number of events 1 • Up to 5 years and 4 months
Investigations Creatinine increased	0.00% 0/4 • Up to 5 years and 4 months	50.0% 2/4 • Number of events 2 • Up to 5 years and 4 months	0.00% 0/6 • Up to 5 years and 4 months
Investigations Alkaline phosphatase increased	0.00% 0/4 • Up to 5 years and 4 months	0.00% 0/4 • Up to 5 years and 4 months	16.7% 1/6 • Number of events 1 • Up to 5 years and 4 months
Metabolism and nutrition disorders Anorexia	50.0% 2/4 • Number of events 2 • Up to 5 years and 4 months	0.00% 0/4 • Up to 5 years and 4 months	0.00% 0/6 • Up to 5 years and 4 months
Metabolism and nutrition disorders Hypercalcemia	25.0% 1/4 • Number of events 1 • Up to 5 years and 4 months	0.00% 0/4 • Up to 5 years and 4 months	0.00% 0/6 • Up to 5 years and 4 months
Metabolism and nutrition disorders Hyperkalemia	0.00% 0/4 • Up to 5 years and 4 months	0.00% 0/4 • Up to 5 years and 4 months	16.7% 1/6 • Number of events 1 • Up to 5 years and 4 months
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/4 • Up to 5 years and 4 months	25.0% 1/4 • Number of events 1 • Up to 5 years and 4 months	0.00% 0/6 • Up to 5 years and 4 months
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/4 • Up to 5 years and 4 months	25.0% 1/4 • Number of events 1 • Up to 5 years and 4 months	0.00% 0/6 • Up to 5 years and 4 months
Nervous system disorders Dysgeusia	25.0% 1/4 • Number of events 1 • Up to 5 years and 4 months	0.00% 0/4 • Up to 5 years and 4 months	0.00% 0/6 • Up to 5 years and 4 months
Nervous system disorders Dizziness	0.00% 0/4 • Up to 5 years and 4 months	0.00% 0/4 • Up to 5 years and 4 months	16.7% 1/6 • Number of events 1 • Up to 5 years and 4 months
Nervous system disorders Headache	0.00% 0/4 • Up to 5 years and 4 months	0.00% 0/4 • Up to 5 years and 4 months	16.7% 1/6 • Number of events 1 • Up to 5 years and 4 months
Psychiatric disorders Insomnia	25.0% 1/4 • Number of events 1 • Up to 5 years and 4 months	0.00% 0/4 • Up to 5 years and 4 months	0.00% 0/6 • Up to 5 years and 4 months
Respiratory, thoracic and mediastinal disorders Epistaxis	25.0% 1/4 • Number of events 1 • Up to 5 years and 4 months	0.00% 0/4 • Up to 5 years and 4 months	0.00% 0/6 • Up to 5 years and 4 months
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/4 • Up to 5 years and 4 months	50.0% 2/4 • Number of events 2 • Up to 5 years and 4 months	16.7% 1/6 • Number of events 1 • Up to 5 years and 4 months
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/4 • Up to 5 years and 4 months	25.0% 1/4 • Number of events 1 • Up to 5 years and 4 months	0.00% 0/6 • Up to 5 years and 4 months
Vascular disorders Hot flashes	0.00% 0/4 • Up to 5 years and 4 months	25.0% 1/4 • Number of events 1 • Up to 5 years and 4 months	16.7% 1/6 • Number of events 1 • Up to 5 years and 4 months
General disorders Pain	25.0% 1/4 • Number of events 1 • Up to 5 years and 4 months	0.00% 0/4 • Up to 5 years and 4 months	0.00% 0/6 • Up to 5 years and 4 months
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	25.0% 1/4 • Number of events 1 • Up to 5 years and 4 months	0.00% 0/4 • Up to 5 years and 4 months	0.00% 0/6 • Up to 5 years and 4 months
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other	25.0% 1/4 • Number of events 1 • Up to 5 years and 4 months	0.00% 0/4 • Up to 5 years and 4 months	0.00% 0/6 • Up to 5 years and 4 months

Additional Information

Debasish Tripathy

M D Anderson Cancer Center

Phone: 713-794-4385

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	HCQ at 400 mg n=4 Participants 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.	HCQ at 600 mg n=5 Participants 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.	HCQ at 800 mg n=6 Participants 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.	Total n=15 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	4 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants	15 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants	15 Participants n=4 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	4 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants	15 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) White	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants	12 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Region of Enrollment United States	4 participants n=5 Participants	5 participants n=7 Participants	6 participants n=5 Participants	15 participants n=4 Participants