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.

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.

Breast Cancer

Invasive Breast Cancer

chloroquine 500 mg daily as an oral capsule during the wait time to surgery.

Chloroquine

Placebo

The Ottawa Hospital Woman's Breast Health Centre

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

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

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.

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

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.

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.

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.

Ottawa Hospital Research Institute

Patients treated with a treatment chosen by sensitivity assay in vitro

Lung Cancer

Colorectal Cancer

To test in vitro sensitivity of cancer stem cells to several antineoplastic drugs in order to personalize treatment

Cancer Stem Cells Sensitivity Assay

Department of Medical Oncology

Feasibility Study on Stem Cells Sensitivity Assay

STELLA: a Feasibility Study on Stem Cells Sensitivity Assay

Percentage of patients in which sensitivity assay is feasible

Identification of breast, colo-rectal and lung cancer stem cells by flow cytometric analysis or immunofluorescence

In vitro tumor sensitivity to chemotherapy drugs will be tested on tumor cell cultures per each patient.

To identify drugs potentially effective for a specific patient

Associazione Oncologia Traslazionale

Taxane-Like (Paclitaxel, Docetaxel, Abraxane, Ixabepilone)

Breast Neoplasms

Chloroquine 250mg po daily together with Paclitaxel (Taxane) 175 mg/m2 three hours infusion every three weeks.

Taxane

Chloroquine 250mg po daily together with docetaxel 75 mg/m2 administered intravenously over one hour every three weeks

Docetaxel

Chloroquine 250mg po daily together with Abraxane 260 mg/m2 administered intravenously over 30 minutes every three weeks.

Abraxane

Chloroquine 250mg po daily together with Ixabepilone is 40 mg/m2 administered intravenously over three hours every three weeks.

Ixabepilone

Houston Methodist Hospital Cancer Center

Houston Methodist Hospital Willowbrook

Houston Methodist Hospital Sugar Land

Chloroquine With Taxane Chemotherapy for Advanced or Metastatic Breast Cancer After Anthracycline Failure (CAT)

Phase II Study of The Efficacy And Safety of Chloroquine (C) in CombinAtion With Taxane or Taxane-like (T) Chemo Agents in The Treatment of Patients With Advanced or Metastatic Breast Cancer Who Have Failed Anthracycline Chemo Base Therapy.

To determine the anti-tumor activity of the combination of Chloroquine + Taxane or Taxane-like chemo agents (Paclitaxel, Docetaxel, Abraxane, Ixabepilone) (C/T) measured by overall Response Rate (ORR).

To assess the safety and tolerability of the combination of Chloroquine and Taxane or Taxane-Like chemo.

To assess the response rate and tumor control rate (TCR) of patients receiving Chloroquine + Taxane or Taxane-like.

To assess the Time to Progression (TTP) of patients receiving Chloroquine + Taxane or Taxane-like chemo.

To assess the duration of response (DOR) of patients receiving Chloroquine + Taxane or Taxane-like chemo agents.

Jenny C. Chang, MD

Sponsor-Investigator/Principal Investigator

The Methodist Hospital System

Between tumor biopsy and surgery, during 2-3 weeks, breast cancer patients will take daily HCQ, an anti-malaria and anti-rheumatic drug that precludes tumor cells from surviving hypoxia by inhibiting the process of autophagy in these cells

800 mg per os once, and then 400 mg per day

Hydrochloroquine

University Medical Centre Nijmegen

Autophagy Inhibition Using Hydrochloroquine in Breast Cancer Patients

Autophagy Inhibition Using Hydrochloroquine in Breast Cancer Patients:a Pilot Study

differences in endogenous hypoxia markers (CA9, PAI-1, VEGF [Rademakers et al. 2008]) and autophagy (LC3b [Rouschop et al. 2010]) before and after treatment with HCQ. These parameters will be quantified by immunohistochemistry on formalin fixed paraffin embedded tissue from both pretreatment biopsy, and posttreatment surgically obtained material.

differences in putative crucial mediators in the autophagy pathway currently under investigation, i.e. TRB3, ATF4, GRP78, LAMP3, etc.before and after short-term pre-surgical treatment with HCQ

chloroquine/tumori dojke

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

Feasibility Study on Stem Cells Sensitivity Assay

Chloroquine With Taxane Chemotherapy for Advanced or Metastatic Breast Cancer After Anthracycline Failure (CAT)

Autophagy Inhibition Using Hydrochloroquine in Breast Cancer Patients

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