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

NCT01446016 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: Pro000064230811-0147
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 3

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).

Conditions

Breast Neoplasms; Breast Cancer

Keywords

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; Chloroquine; Paclitaxel; Taxol; Ixabepilone; Abraxane; Metastatic Breast Cancer; Advanced Breast Cancer; Anthracycline

Outcome Measures

Primary Outcomes (1)

• 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).

  3-week cycles for maximum of 6 cycles (4.5 months)

Secondary Outcomes (3)

• Time to Progression Free Survival (PFS)

  25.4 months (median)

• Time of Overall Survival (OS)

  a median of 25.4 months, up to 83.5 months

• Number of Patients Who Experienced Grade 3 of Greater Adverse Events

  25.4 months (median)

Study Arms (1)

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

EXPERIMENTAL

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.

Drug: Paclitaxel; Drug: Docetaxel; Drug: Abraxane; Drug: Ixabepilone

Interventions

Paclitaxel DRUG

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

Also known as: Taxane

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

Docetaxel DRUG

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

Also known as: Taxane

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

Abraxane DRUG

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

Also known as: Taxane-like

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

Ixabepilone DRUG

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

Also known as: Taxane-like

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

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Females with pathologically determined advanced or metastatic breast cancer.
• Have progressed after treatment with regimen that included an anthracycline.
• Have had at least 4 cycles of an anthracycline containing regimen or 2 cycles if progressing on treatment.
• Patients must have measurable disease by Response Evaluation Criteria in Solid Tumors.
• ≥18 years of age.
• ECOG PS of 0, 1, or 2.
• 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
• 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.
• 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.
• Patient must be willing to undergo breast biopsies as required by the study protocol.

You may not qualify if:

• Radiation therapy within 2 weeks; or chemotherapy or non-cytotoxic investigational agents within 4 weeks of initiating study treatment.
• Evidence of New York Heart Association class III or greater cardiac disease.
• History of myocardial infarction, stroke, ventricular arrhythmia, or symptomatic conduction abnormality within 12 months.
• History of congenital QT prolongation.
• QT \>500.
• 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.
• Symptomatic central nervous system metastases. The patient must be stable after radiotherapy for ≥2 weeks and off corticosteroids for ≥1 week.
• Pregnant or nursing women.
• Hypersensitivity or intolerance to Chloroquine, Paclitaxel, Docetaxel, Abraxane, Ixabepilone or other Taxane like drugs.
• Severe renal insufficiency (CrCl \<30mL/min \[Cockcroft and Gault\]).
• History of gastrointestinal bleeding, ulceration, or perforation.
• Concurrent use of potent CYP3A4 inhibitors, such as ketoconazole, itraconazole,clarithromycin, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, and voriconazole.
• Concurrent use of potent CYP3A4 inducers, such as dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbitol, and St. John's wort.

Sponsors & Collaborators

• The Methodist Hospital Research Institute: lead

Study Sites (3)

Houston Methodist Hospital Cancer Center

Houston, Texas, 77030, United States

Location

Houston Methodist Hospital Willowbrook

Houston, Texas, 77070, United States

Location

Houston Methodist Hospital Sugar Land

Sugar Land, Texas, 77479, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Paclitaxel; taxane; Docetaxel; Albumin-Bound Paclitaxel; ixabepilone

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Dr. Jenny Chang
• Organization: Houston Methodist

jcchang@houstonmethodist.org

713-441-0681

Study Officials

• Jenny C Chang, MD

  The Methodist Hospital Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 29, 2011
• First Posted: October 4, 2011
• Study Start: September 1, 2011
• Primary Completion: March 1, 2019
• Study Completion: March 1, 2019
• Last Updated: January 23, 2023
• Results First Posted: February 1, 2022

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)