Clinical Trials /

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

NCT02414776

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Terminated

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Hydroxychloroquine in Metastatic Estrogen Receptor-Positive Breast Cancer Progressing on Hormonal Therapy
  • Official Title: Phase Ib/II Study of Hydroxychloroquine in Metastatic ER-Positive Breast Cancer Progressing on Hormonal Therapy

Clinical Trial IDs

  • ORG STUDY ID: WIRB 20140460
  • NCT ID: NCT02414776

Conditions

  • Estrogen Receptor Positive Breast Cancer

Interventions

DrugSynonymsArms
hydroxychloroquinePlaquenilhydroxychloroquine plus hormonal therapy

Purpose

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.

Detailed Description

      To determine the number of patients with adverse effects

      To assess the clinical response to the combination
    

Trial Arms

NameTypeDescriptionInterventions
hydroxychloroquine plus hormonal therapyExperimentalAdd hydroxychloroquine to the current hormonal therapy
  • hydroxychloroquine

Eligibility Criteria

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Participants with Adverse Events as a Measure of the safety profile of orally administered hydroxychloroquine with hormonal therapy
Time Frame:18 months
Safety Issue:
Description: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

Secondary Outcome Measures

Measure:The recommended phase 2 clinical dose (RP2D) of orally administered hydroxychloroquine with hormonal therapy
Time Frame:18 months
Safety Issue:
Description:orally administered hydroxychloroquine with hormonal therapy
Measure:The pharmacodynamic (PD) profile of hydroxychloroquine with hormonal therapy
Time Frame:18 months
Safety Issue:
Description:microtubule-associated protein 1 light chain 3 b (LC3b) level in the biopsy, WBCs in pre- and post-treatment samples
Measure: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)
Time Frame:18 months
Safety Issue:
Description: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)
Measure:The disease-free survival (DFS) when adding hydroxychloroquine to hormonal therapy
Time Frame:18 months
Safety Issue:
Description:The disease-free survival (DFS) when adding hydroxychloroquine to hormonal therapy

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Terminated
Lead Sponsor:Western Regional Medical Center

Last Updated

September 25, 2017