Hydroxychloroquine in Metastatic Estrogen Receptor-Positive Breast Cancer Progressing on Hormonal Therapy

Estrogen Receptor Positive Breast Cancer Clinical Trial

— ABC01  

Official title:

Phase Ib/II Study of Hydroxychloroquine in Metastatic ER-Positive Breast Cancer Progressing on Hormonal Therapy

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02414776
• Other study ID #: WIRB 20140460
• Status: Terminated
• Phase: Phase 1
• First received: January 19, 2015
• Last updated: September 25, 2017
• Start date: July 2014
• Est. completion date: November 2015

Study information

• Verified date: September 2017
• Source: Western Regional Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To determine the safety and tolerability of orally administered hydroxychloroquine with hormonal therapy.

To assess the response rate of hydroxychloroquine in combination with hormonal therapy.

Description:

To determine the number of patients with adverse effects

To assess the clinical response to the combination

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: November 2015
• Est. primary completion date: November 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Patients = 18 years of age with histologically confirmed, metastatic ER + breast cancer with clinical progression of disease (including radiographically stable disease with at least 50% increment of an elevated tumor marker by two measurements at least 2 weeks apart (this particular tumor marker will be used for disease status assessment in the study) on current hormonal therapy with PFS for at least 3 months.

2. Karnofsky Performance Status (KPS) =70% and a life expectancy >3 months.

3. Participants must have at least one target visceral lesion that allows for evaluation of tumor response or in the case of bone-only metastases, patients need to have a positive imaging study such as bone scan, magnetic resonance imaging (MRI) or positron emission tomography-computed tomography (PET-CT) or CT, and an elevated tumor marker at least twice as high as upper limit.

4. Absolute neutrophil count > 1500 mm3, platelet count = 80×109 L, hemoglobin = 8.5 g/dL

5. Creatinine clearance = 30 mL/min, total bilirubin = 2 mg/dL, AST/ALT = 3 times the upper limit of normal range

6. No remaining grade 2 or higher toxicity from prior cancer therapies unless judged to be clinically insignificant by the Principal Investigator

7. At least two (2) weeks from prior major surgery

8. Willingness to provide permission to biopsy one of the lesions if applicable before the study (All the patients are encouraged to have post-therapy biopsy upon progression of disease, but it is optional) as well as blood samples for pertinent laboratory studies

9. Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically sterile) must be willing to use an acceptable non-hormonal contraceptive method (abstinence, or double barrier method) for the duration of the study and for 30 days following the last dose of study drug, and must have a negative urine or serum pregnancy test within 2 weeks prior to beginning treatment on this trial -

Exclusion Criteria:

1. On combination hormonal therapy with everolimus or any other investigational agent

2. Patients have symptomatic untreated brain metastasis or leptomeningeal metastases or treated but still symptomatic requiring the use of steroid 18Jul2014 Protocol v3: ABC 01 Anti-Autophagy for Met Breast Cancer Page 4 of 16

3. Lymphangitic carcinomatosis involving = 50% of the lungs; evidence of metastases involving more than one third of the liver on sonogram or computed tomography

4. Lactating females

5. Uncontrolled cardiac disease, congestive heart failure, angina or hypertension

6. Myocardial infarction or unstable angina within 2 months of treatment

7. Known human immunodeficiency virus (HIV) infection or chronic active Hepatitis B or C (patients are NOT required to be tested for the presence of such viruses prior to therapy on this protocol)

8. Active clinically serious infection > CTCAE (version 4.03) Grade 2

9. Serious non-healing wound, ulcer, or bone fracture

10. Concurrent psychiatric illness/social situations that would limit safety and compliance with study requirements

11. Inability to complete informed consent process and adhere to the protocol treatment plan and follow-up requirements

12. Currently receiving any other investigational therapeutic agents

13. Patients with known glucose-6-phosphate dehydrogenase deficiency, porphyria, cirrhosis or any other conditions with potential significant known risks

14. Patients with history of retinal damage

Related Conditions & MeSH terms

• Breast Neoplasms
• Estrogen Receptor Positive Breast Cancer

Intervention

Drug:
• hydroxychloroquine
administration of hydroxychloroquine in combination with the current hormonal therapy

Locations

Country	Name	City	State
United States	Western Regional Medical Center, Inc.	Goodyear	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Western Regional Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants with Adverse Events as a Measure of the safety profile of orally administered hydroxychloroquine with hormonal therapy	Assess the dose-limiting side effects such as neutropenia, anemia, or thormbocytopenia, or non-hematologic side effects nausea, vomiting, diarrhea, or vision problems at the study dose	18 months
Secondary	The recommended phase 2 clinical dose (RP2D) of orally administered hydroxychloroquine with hormonal therapy	orally administered hydroxychloroquine with hormonal therapy	18 months
Secondary	The pharmacodynamic (PD) profile of hydroxychloroquine with hormonal therapy	microtubule-associated protein 1 light chain 3 b (LC3b) level in the biopsy, WBCs in pre- and post-treatment samples	18 months
Secondary	The anti-tumor activity of hydroxychloroquine with hormonal therapy with clinical benefit rate (CBR). Clinical benefits are defined as complete remission (CR), partial remission (PR) and stable disease (SD)	The anti-tumor activity of hydroxychloroquine with hormonal therapy with clinical benefit rate (CBR). Clinical benefits are defined as complete remission (CR), partial remission (PR) and stable disease (SD)	18 months
Secondary	The disease-free survival (DFS) when adding hydroxychloroquine to hormonal therapy	The disease-free survival (DFS) when adding hydroxychloroquine to hormonal therapy	18 months