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

Condition(s) targeted: Breast Cancer; Invasive Breast Cancer

Intervention: Chloroquine (Drug); Placebo (Drug)

Phase: Phase 2

Status: Not yet recruiting

Sponsored by: Ottawa Hospital Research Institute

Official(s) and/or principal investigator(s):
Angel Arnaout, MD, Principal Investigator, Affiliation: The Ottawa Hospital

Overall contact:
Angel Arnaout, MD, Phone: 613-798-5555, Email: anarnaout@toh.on.ca

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.

Official title: 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

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Primary outcome: Effect of a brief course of CQ on tumour proliferation and apoptosis

Secondary outcome:

Measure of Circulating CQ Metabolites

Autophagic Markers in Cancerous and Stromal Tissue

Detailed description: 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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Female.

Criteria:

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.

Angel Arnaout, MD, Phone: 613-798-5555, Email: anarnaout@toh.on.ca

The Ottawa Hospital Woman's Breast Health Centre, Ottawa, Ontario, Canada

Starting date: May 2015
Last updated: April 21, 2015