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

NCT ID: NCT01446016

Last Updated: 2023-01-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 38 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-09-30
• Study Completion Date: 2019-03-01

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.

Conditions

Breast Neoplasms; Breast Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Chloroquine with Taxane or Taxane-Like (Paclitaxel, Docetaxel, Abraxane, Ixabepilone) Chemotherapy

Chloroquine (250 mg) was given daily orally with either Paclitaxel or Docetaxel or Abraxane or Ixabepilone chemotherapy every 3 weeks (1 cycle) fro a maximum of 6 cycles.

Group Type: EXPERIMENTAL

Paclitaxel

Intervention Type: DRUG

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

Docetaxel

Intervention Type: DRUG

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

Abraxane

Intervention Type: DRUG

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

Ixabepilone

Intervention Type: DRUG

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

Interventions

Paclitaxel

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

Intervention Type: DRUG

Docetaxel

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

Intervention Type: DRUG

Abraxane

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

Intervention Type: DRUG

Ixabepilone

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

Intervention Type: DRUG

Other Intervention Names

Taxane; Taxane; Taxane-like; Taxane-like

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

The Methodist Hospital Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Jenny C. Chang, MD

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jenny C Chang, MD

Role: PRINCIPAL_INVESTIGATOR

The Methodist Hospital Research Institute

Locations

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

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

0811-0147

Identifier Type: OTHER

Identifier Source: secondary_id

Pro00006423

Identifier Type: -

Identifier Source: org_study_id