Chloroquine With Taxane Chemotherapy for Advanced or Metastatic Breast Cancer Patients Who Have Failed an Anthracycline (CAT)

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by The Methodist Hospital System
Sponsor:
Information provided by (Responsible Party):
The Methodist Hospital System
ClinicalTrials.gov Identifier:
NCT01446016
First received: September 29, 2011
Last updated: February 18, 2014
Last verified: February 2014
  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 Intervention Phase
Breast Neoplasms
Breast Cancer
Drug: Taxane
Drug: Taxotere
Drug: Abraxane
Drug: Ixabepilone
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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.

Resource links provided by NLM:


Further study details as provided by The Methodist Hospital System:

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).


Secondary Outcome Measures:
  • Safety and Tolerability [ Time Frame: One Year ] [ Designated as safety issue: Yes ]
    To assess the safety and tolerability of the combination of Chloroquine and Taxane or Taxane-Like chemo.

  • Tumor Control Rate [ Time Frame: One Year ] [ Designated as safety issue: No ]
    To assess the response rate and tumor control rate (TCR) of patients receiving Chloroquine + Taxane or Taxane-like.

  • Time to Progression [ Time Frame: One Year ] [ Designated as safety issue: No ]
    To assess the Time to Progression (TTP) of patients receiving Chloroquine + Taxane or Taxane-like chemo.

  • Duration of Response [ Time Frame: Three Years ] [ Designated as safety issue: No ]
    To assess the duration of response (DOR) of patients receiving Chloroquine + Taxane or Taxane-like chemo agents.


Estimated Enrollment: 47
Study Start Date: September 2011
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Taxane
Taxane
Drug: Taxane
Chloroquine 250mg po daily together with Paclitaxel (Taxane) 175 mg/m2 three hours infusion every three weeks.
Other Name: Paclitaxel
Active Comparator: Taxane-Like
Taxane-Like (Paclitaxel, Docetaxel, Abraxane, Ixabepilone)
Drug: Taxotere
Chloroquine 250mg po daily together with Taxotere 75 mg/m2 administered intravenously over one hour every three weeks
Other Name: Taxne-like
Drug: Abraxane
Chloroquine 250mg po daily together with Abraxane 260 mg/m2 administered intravenously over 30 minutes every three weeks.
Other Name: Taxane-like
Drug: Ixabepilone
Chloroquine 250mg po daily together with Ixabepilone is 40 mg/m2 administered intravenously over three hours every three weeks.
Other Name: Taxane-like

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01446016

Contacts
Contact: Cancer Center Research 713-441-0629 ccresearch@tmhs.org

Locations
United States, Texas
The Methodist Hospital Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Cancer Center Research    713-441-0629    ccresearch@houstonmethodist.org   
Principal Investigator: Jenny Chang, MD         
Sub-Investigator: Angel A. Rodriguez, MD         
Sub-Investigator: Daniel Lehane, MD         
Sub-Investigator: Monisha Singh, MD         
Sub-Investigator: Tejal Patel, MD         
Sub-Investigator: Jorge Darcourt, MD         
Sponsors and Collaborators
The Methodist Hospital System
Investigators
Principal Investigator: Jenny C Chang, MD The Methodist Hospital System
  More Information

No publications provided

Responsible Party: The Methodist Hospital System
ClinicalTrials.gov Identifier: NCT01446016     History of Changes
Other Study ID Numbers: 0811-0147
Study First Received: September 29, 2011
Last Updated: February 18, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by The Methodist Hospital System:
Breast Cancer
Breast Tumors
Cancer of Breast
Cancer of the Breast
Human Mammary Carcinoma
Mammary Carcinoma, Human
Mammary Neoplasm, Human
Mammary Neoplasms, Human
Neoplasms, Breast
Tumors, Breast
Taxotere
Chloroquine
Paclitaxel
Taxol
Ixabepilone
Abraxane
Metastatic Breast Cancer
Advanced Breast Cancer
Anthracycline

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Chloroquine
Chloroquine diphosphate
Paclitaxel
Docetaxel
Taxane
Amebicides
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antimalarials
Antirheumatic Agents
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Filaricides
Antinematodal Agents
Anthelmintics
Central Nervous System Agents
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on September 11, 2014