The major purpose of this research study is to better understand how therapy works on different patients. This study is being offered to patients with a diagnosis of advanced or metastatic breast cancer who have failed anthracycline based therapy. The investigators want to see the response of breast cancer cell when treated with Chloroquine used in combination with chemotherapy. Chemotherapy is an anti-cancer drug that is given through your vein. The chemotherapy used in this study is either Taxane (Paclitaxel) or Taxane-like drugs (Abraxane, Ixabepilone or Docetaxel).
The purpose of this study is to determine the anti-tumor activity of the combination of Chloroquine combined with a Taxane or Taxane-like chemo agents(Paclitaxel, Docetaxel, Abraxane, Ixabepilone). The laboratories have developed robust preclinical models utilizing both in vitro systems such as the mammosphere (MS) culture and in vivo systems such as human breast cancer xenografts allowing the investigators to identify agents which selectively target TICs, as single agents or in combination. These models are critical since tumor initiating cells (TICs) comprise only a small percentage of the tumor bulk, so that clinical tumor regression may not be observed with inhibitors that selectively target TIC self-renewal alone. Nonetheless, these agents in combination with conventional therapy may effectively kill both actively cycling or fully differentiated cells and the TIC subpopulation, leading to long term remission and eradication of cancer cells.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
38
Chloroquine 250mg po daily together with Paclitaxel (Taxane) 175 mg/m2 three hours infusion every three weeks.
Chloroquine 250mg po daily together with docetaxel 75 mg/m2 administered intravenously over one hour every three weeks
Chloroquine 250mg po daily together with Abraxane 260 mg/m2 administered intravenously over 30 minutes every three weeks.
Chloroquine 250mg po daily together with Ixabepilone is 40 mg/m2 administered intravenously over three hours every three weeks.
Houston Methodist Hospital Cancer Center
Houston, Texas, United States
Houston Methodist Hospital Willowbrook
Houston, Texas, United States
Houston Methodist Hospital Sugar Land
Sugar Land, Texas, United States
Overall Response Rate (ORR)
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) defined as percentage of patients having complete or partial response in therapy per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.", or similar definition that is accurate and appropriate. The study was designed to compare the ORR with the published percentage of 30% (docetaxel 100 mg/ml2 every 3 weeks for maximum of 10 cycles).
Time frame: 3-week cycles for maximum of 6 cycles (4.5 months)
Time to Progression Free Survival (PFS)
To assess the time to progression free survival of patients treated with the combination of Chloroquine and Taxane or Taxane-Like chemotherapy. Progression is defined as time from initiation of chemotherapy to disease progression using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions", or similar definition as accurate and appropriate.
Time frame: 25.4 months (median)
Time of Overall Survival (OS)
To assess the time of overall survival of patients receiving Chloroquine + Taxane or Taxane-like chemotherapy
Time frame: a median of 25.4 months, up to 83.5 months
Number of Patients Who Experienced Grade 3 of Greater Adverse Events
To assess how many patients experienced grade 3 or greater adverse events when receiving the combination of Chloroquine and Taxane or Taxane-Like chemotherapy. Toxicity was assessed for all enrolled patients who received one or more doses of the study drug combination by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Time frame: 25.4 months (median)
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