A Phase 2 Randomized, Double-blind Trial Evaluating the Effects of Chloroquine in Breast Cancer

Study Overview
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Brief Summary
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Chloroquine (CQ) is a well known, well tolerated medication that has been used for many years traditionally for arthritis, lupus, and malaria. It has anti-inflammatory properties but is often the drug of choice for arthritis and malaria due to its few side effects. Recently, laboratory investigations have proven that CQ may potentially have anti-cancer properties, by inhibiting a process which allows cancers such as breast cancer to continue to grow (a process known as autophagy). Therefore, this study will look at how well CQ can inhibit the growth of breast cancers in patients while waiting for surgery.

Detailed Description
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Patients diagnosed with breast cancer can sometimes wait up to 6 weeks for their surgery. The wait leading up to surgery is a potentially long and anxious time. Since no treatment is happening during this period anyway, this study will allow patients to receive CQ during this waiting period. This study will compare CQ treatment before surgery with the standard approach during this time, which is no treatment. Although CQ is widely used for the treatment of arthritis and malaria, CQ is considered investigational for use in breast cancer. The study will NOT interfere with the routine assessments as part of the pre-operative care, NOR will it delay the date of surgery. This study compares the effects of the CQ to placebo. Participants will be randomized 1:1 and be provided with the blinded placebo or QC (500mg daily) during the wait time. Biomarker testing will be performed on the initial biopsy tissue and at the time of surgery as well as blood work. There is also an opportunity for participants to enrol in the optional sample collection for future research.

Official Title
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A Phase 2 Randomized, Double-blind, Window of Opportunity Trial Evaluating Clinical and Correlative Effects of Chloroquine as a Novel Therapeutic Strategy in Breast Cancer

Conditions
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Breast Cancer, Invasive Breast Cancer

Intervention / Treatment
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* Drug: Chloroquine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: newly diagnosed histologically confirmed primary invasive breast cancer who is currently not undergoing any treatment while awaiting surgery in the next 2-6 weeks tumour ≥ 1.5 cm by palpation or imaging ECOG performance status 0-2 written informed consent for the study Exclusion Criteria: Known Metastatic breast cancer history of pre-existing known retinal or ocular pathology patient has only one functioning eye abnormal hepatic function (serum AST or ALT >3x upper limit of normal) currently on CQ or HCQ or has been on the drug within the past 3 months for other conditions known history of psoriasis known history of epilepsy or seizures electrocardiogram showing QT prolongation based on QTc interval >450 ms inability to comply with a study protocol (abuse of alcohol, drugs or psychotic states) current known pregnancy or actively nursing allergic reactions to quinolones or CQ inability to consent.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Chloroquine<br>The daily oral dose per patient is 500 mg of chloroquine. Patients may be taking the drug for 2-6 weeks leading up to the date of the surgery. The last dose will be taken the evening before surgery. | Drug: Chloroquine<br>* chloroquine 500 mg daily as an oral capsule during the wait time to surgery.<br>|
| Placebo Comparator: Placebo<br>The daily oral dose per patient is 500 mg of placebo (lactose). Patients may be taking the drug for 2-6 weeks leading up to the date of the surgery. The last dose will be taken the evening before surgery. | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of a brief course of CQ on tumour proliferation and apoptosis | We will assess relative changes in proliferative and apoptotic response indices based on Ki67 and TUNEL assays in primary breast cancer biopsies pre- and post-treatment with CQ, as these changes occur more rapidly than gross changes in tumour volume. | baseline and at 2-6 weeks, the day of surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measure of Circulating CQ Metabolites | Plasma samples collected at baseline and at surgery will be assessed for levels of CQ and its metabolite desethylchloroquine (DECQ) by high-performance liquid chromatography (HPLC) as described | baseline and at 2-6 weeks, the day of surgery | 
| Autophagic Markers in Cancerous and Stromal Tissue | Immunohistochemical detection of proteins such as Beclin 1, LC3, and p62 which are required for autophagosome formation have been extensively studied in clinical tumour samples, and will be assessed in participant samples pre and post-CQ treatment. | baseline and at 2-6 weeks, the day of surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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breast