Chloroquine With Taxane Chemotherapy for Advanced or Metastatic Breast Cancer Patients Who Have Failed an Anthracycline (CAT)
Overview[ - collapse ][ - ]
| Purpose | 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). |
|---|---|
| Condition | Breast Neoplasms Breast Cancer |
| Intervention | Drug: Taxane Drug: Taxotere Drug: Abraxane Drug: Ixabepilone |
| Phase | Phase 2 |
| Sponsor | The Methodist Hospital System |
| Responsible Party | The Methodist Hospital System |
| ClinicalTrials.gov Identifier | NCT01446016 |
| First Received | September 29, 2011 |
| Last Updated | February 18, 2014 |
| Last verified | February 2014 |
Tracking Information[ + expand ][ + ]
| First Received Date | September 29, 2011 |
|---|---|
| Last Updated Date | February 18, 2014 |
| Start Date | September 2011 |
| Estimated Primary Completion Date | Not Provided |
| Current Primary Outcome Measures | Overall Response Rate (ORR) [Time Frame: One Year] [Designated as safety issue: No]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). |
| Current Secondary Outcome Measures |
|
Descriptive Information[ + expand ][ + ]
| Brief Title | Chloroquine With Taxane Chemotherapy for Advanced or Metastatic Breast Cancer Patients Who Have Failed an Anthracycline (CAT) |
|---|---|
| Official Title | 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. |
| Brief Summary | 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). |
| Detailed Description | 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 |
| Study Phase | Phase 2 |
| Study Design | Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment |
| Condition |
|
| Intervention | Drug: Taxane Chloroquine 250mg po daily together with Paclitaxel (Taxane) 175 mg/m2 three hours infusion every three weeks. Other Names: PaclitaxelDrug: Taxotere Chloroquine 250mg po daily together with Taxotere 75 mg/m2 administered intravenously over one hour every three weeks Other Names: Taxne-likeDrug: Abraxane Chloroquine 250mg po daily together with Abraxane 260 mg/m2 administered intravenously over 30 minutes every three weeks. Other Names: Taxane-likeDrug: Ixabepilone Chloroquine 250mg po daily together with Ixabepilone is 40 mg/m2 administered intravenously over three hours every three weeks. Other Names: Taxane-like |
| Study Arm (s) |
|
Recruitment Information[ + expand ][ + ]
| Recruitment Status | Recruiting |
|---|---|
| Estimated Enrollment | 47 |
| Estimated Completion Date | Not Provided |
| Estimated Primary Completion Date | September 2015 |
| Eligibility Criteria | Inclusion Criteria: 1. Females with pathologically determined advanced or metastatic breast cancer. 2. Have progressed after treatment with regimen that included an anthracycline. 3. Have had at least 4 cycles of an anthracycline containing regimen or 2 cycles if progressing on treatment. 4. Patients must have measurable disease by Response Evaluation Criteria in Solid Tumors. 5. ≥18 years of age. 6. ECOG PS of 0, 1, or 2. 7. Laboratory values within the following ranges: - Hemoglobin ≥9.0gm/dL (≥1.5μmol/L); transfusions permitted. - Absolute neutrophil count ≥1500/mm3 (1.5 x 109/L) - Platelet count ≥100,000/mm3 (100 x 109/L) - Creatinine (Cr) <2 X the upper limit of normal (ULN), Cr clearance (CrCl) ≥30 by Cockcroft and Gault - Alanine aminotransferase and aspartate aminotransferase <2 X the ULN; if liver metastases are present then must be <5 X the ULN, Bilirubin <2 X the ULN, Potassium within normal limits, Magnesium within normal limits 8. Negative serum pregnancy test at the time of first dose for women of childbearing potential (WOCBP). For WOCBP, adequate contraception must be used throughout the study. For this study, acceptable methods of contraception include a reliable intrauterine device or a spermicide in combination with a barrier method. Women who are already on hormonal forms of birth control may continue that treatment but must also use a barrier method. 9. Ability to understand the requirements of the study, provide written informed consent and authorization of use and disclosure of protected health information, and agree to abide by the study restrictions and return for the required assessments. 10. Patient must be willing to undergo breast biopsies as required by the study protocol. Exclusion Criteria: 1. Radiation therapy within 2 weeks; or chemotherapy or non-cytotoxic investigational agents within 4 weeks of initiating study treatment. 2. Evidence of New York Heart Association class III or greater cardiac disease. 3. History of myocardial infarction, stroke, ventricular arrhythmia, or symptomatic conduction abnormality within 12 months. 4. History of congenital QT prolongation. 5. QT >500. 6. Concurrent severe or uncontrolled medical disease (i.e., active systemic infection, diabetes, hypertension, coronary artery disease, congestive heart failure) that, in the opinion of the Investigator, would compromise the safety of the patient or compromise the ability of the patient to complete the study. 7. Symptomatic central nervous system metastases. The patient must be stable after radiotherapy for ≥2 weeks and off corticosteroids for ≥1 week. 8. Pregnant or nursing women. 9. Hypersensitivity or intolerance to Chloroquine, Paclitaxel, Docetaxel, Abraxane, Ixabepilone or other Taxane like drugs. 10. Severe renal insufficiency (CrCl <30mL/min [Cockcroft and Gault]). 11. History of gastrointestinal bleeding, ulceration, or perforation. 12. Concurrent use of potent CYP3A4 inhibitors, such as ketoconazole, itraconazole,clarithromycin, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, and voriconazole. 13. Concurrent use of potent CYP3A4 inducers, such as dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbitol, and St. John's wort. |
| Gender | Female |
| Ages | 18 Years |
| Accepts Healthy Volunteers | No |
| Contacts | Contact: Cancer Center Research 713-441-0629 ccresearch@tmhs.org |
| Location Countries | United States |
Administrative Information[ + expand ][ + ]
| NCT Number | NCT01446016 |
|---|---|
| Other Study ID Numbers | 0811-0147 |
| Has Data Monitoring Committee | No |
| Information Provided By | The Methodist Hospital System |
| Study Sponsor | The Methodist Hospital System |
| Collaborators | Not Provided |
| Investigators | Principal Investigator: Jenny C Chang, MD The Methodist Hospital System |
| Verification Date | February 2014 |
Locations[ + expand ][ + ]
| The Methodist Hospital Cancer Center | Houston, Texas, United States, 77030 Contact: Cancer Center Research | 713-441-0629 | ccresearch@houstonmethodist.orgPrincipal Investigator: Jenny Chang, MD Recruiting |
|---|