A Phase 2 Randomized, Double-blind Trial Evaluating the Effects of Chloroquine in Breast Cancer (CUBiC)
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|ClinicalTrials.gov Identifier: NCT02333890|
Recruitment Status : Unknown
Verified November 2016 by Ottawa Hospital Research Institute.
Recruitment status was: Recruiting
First Posted : January 7, 2015
Last Update Posted : November 18, 2016
|Condition or disease||Intervention/treatment||Phase|
|Breast Cancer Invasive Breast Cancer||Drug: Chloroquine Drug: Placebo||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||60 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Triple (Participant, Care Provider, Investigator)|
|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 Start Date :||July 2015|
|Estimated Primary Completion Date :||March 2017|
|Estimated Study Completion Date :||March 2018|
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.
chloroquine 500 mg daily as an oral capsule during the wait time to surgery.
Placebo Comparator: Placebo
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.
- Effect of a brief course of CQ on tumour proliferation and apoptosis [ Time Frame: baseline and at 2-6 weeks, the day of surgery ]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.
- Measure of Circulating CQ Metabolites [ Time Frame: baseline and at 2-6 weeks, the day of surgery ]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
- Autophagic Markers in Cancerous and Stromal Tissue [ Time Frame: baseline and at 2-6 weeks, the day of surgery ]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.
- Assessment of Toxicity of CQ in Breast Cancer Patients [ Time Frame: baseline and at 2-6 weeks, the day of surgery ]Even through CQ has an excellent safety profile and the dose of 500 mg/day is well within the dosage in which toxicity is measured, all adverse and serious adverse events while on CQ will be monitored as per the study assessments calendar via the Health Canada Pharmacovigilance program, Ottawa Hospital Science Network-REB and Data Safety Monitoring Board. As the most serious adverse events with CQ use are ocular events, the American Academy of Ophthalmology recommends ophthalmologic screening and management of patients on CQ. Given the limited duration patients will be taking CQ, it is not expected that any ocular events will be observed, however, for enhanced safety, we have 3 ophthalmology collaborators and we will mandate intense vigilance with an ophthalmologic screening exam at baseline, at one month post surgery, and a final at 4-6 months after stopping CQ.
- Differential Gene and Expression using Microarray Analysis. [ Time Frame: baseline and at 2-6 weeks, the day of surgery ]The breast cancer tissue collected and stored during this clinical trial will offer a unique opportunity to study the effect of CQ on the biology of human breast tissue. RNA and gene expression levels will be extracted from participant samples that have been treated with CQ. Potential differentially expressed targets will be confirmed by quantitative RT-PCR using specific primers and normalization to endogenous β-actin or GAPDH as controls.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02333890
|Contact: Angel Arnaout, MDfirstname.lastname@example.org|
|The Ottawa Hospital Woman's Breast Health Centre||Recruiting|
|Ottawa, Ontario, Canada|
|Contact: Angel Arnaout, Dr. 613-798-5555|
|Principal Investigator: Angel Arnaout, Dr.|
|Principal Investigator:||Angel Arnaout, MD||The Ottawa Hospital|