Clinical trial NCT02333890: A Phase 2 Randomized, Double-blind Trial Evaluating the Effects of Chloroquine in Breast Cancer
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 type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Breast Cancer
Invasive Breast Cancer
Keywords: breast
Lead sponsor: Ottawa Hospital Research Institute
Sponsor class: OTHER
First posted: 2015-01-07
Enrollment: 60
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility 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.

Primary outcomes:
measure: Effect of a brief course of CQ on tumour proliferation and apoptosis
timeFrame: baseline and at 2-6 weeks, the day of surgery
Secondary outcomes:
measure: Measure of Circulating CQ Metabolites
timeFrame: baseline and at 2-6 weeks, the day of surgery
measure: Autophagic Markers in Cancerous and Stromal Tissue
timeFrame: baseline and at 2-6 weeks, the day of surgery
Other outcomes:
measure: Assessment of Toxicity of CQ in Breast Cancer Patients
timeFrame: baseline and at 2-6 weeks, the day of surgery
measure: Differential Gene and Expression using Microarray Analysis.
timeFrame: baseline and at 2-6 weeks, the day of surgery
Locations:
city: Ottawa
country: Canada
facility: The Ottawa Hospital Woman's Breast Health Centre
state: Ontario
Study officials:
affiliation: The Ottawa Hospital
name: Angel Arnaout, MD
role: PRINCIPAL_INVESTIGATOR
References: