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

• Sponsor: The Methodist Hospital Research Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT01446016
• Collaborator: (none)
• Enrollment: 38
• Locations: 3
• Arm: 1
• Duration (Months): 90
• Patients Per Site: 12.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Breast Neoplasms; Breast Cancer	Drug: Paclitaxel; Drug: Docetaxel; Drug: Abraxane; Drug: Ixabepilone	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 38 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (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
• Study Start Date: Sep 1, 2011
• Actual Primary Completion Date: Mar 1, 2019
• Actual Study Completion Date: Mar 1, 2019

Arms and Interventions

Arm

Intervention/Treatment

Experimental: 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.

Drug: Paclitaxel; Chloroquine 250mg po daily together with Paclitaxel (Taxane) 175 mg/m2 three hours infusion every three weeks.; Other Names: Taxane ; Drug: Docetaxel; Chloroquine 250mg po daily together with docetaxel 75 mg/m2 administered intravenously over one hour every three weeks; Other Names: Taxane ; Drug: Abraxane; Chloroquine 250mg po daily together with Abraxane 260 mg/m2 administered intravenously over 30 minutes every three weeks.; Other Names: Taxane-like ; Drug: Ixabepilone; Chloroquine 250mg po daily together with Ixabepilone is 40 mg/m2 administered intravenously over three hours every three weeks.; Other Names: Taxane-like

Outcome Measures

Primary Outcome Measures

1. Overall Response Rate (ORR) [3-week cycles for maximum of 6 cycles (4.5 months)]

   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).

Secondary Outcome Measures

1. Time to Progression Free Survival (PFS) [25.4 months (median)]

   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.

2. Time of Overall Survival (OS) [a median of 25.4 months, up to 83.5 months]

   To assess the time of overall survival of patients receiving Chloroquine + Taxane or Taxane-like chemotherapy

3. Number of Patients Who Experienced Grade 3 of Greater Adverse Events [25.4 months (median)]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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

1. 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.

2. 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.

3. 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

Locations

	Site	City	State	Country	Postal Code
1	Houston Methodist Hospital Cancer Center	Houston	Texas	United States	77030
2	Houston Methodist Hospital Willowbrook	Houston	Texas	United States	77070
3	Houston Methodist Hospital Sugar Land	Sugar Land	Texas	United States	77479

Sponsors and Collaborators

• The Methodist Hospital Research Institute

Investigators

• Principal Investigator: Jenny C Chang, MD, The Methodist Hospital Research Institute

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jul 10, 2013

More Information

Publications

None provided.

• Responsible Party: Jenny C. Chang, MD, Principal Investigator, The Methodist Hospital Research Institute
• ClinicalTrials.gov Identifier: NCT01446016
• Other Study ID Numbers: Pro00006423; 0811-0147
• First Posted: Oct 4, 2011
• Last Update Posted: Feb 1, 2022
• Last Verified: Jan 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Jenny C. Chang, MD, Principal Investigator, The Methodist Hospital Research Institute: 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
• Additional relevant MeSH terms: Breast Neoplasms; Neoplasms; Paclitaxel; Docetaxel; Albumin-Bound Paclitaxel; Taxane

Study Results

Participant Flow

Recruitment Details	38 patients were enrolled in the study and 31 patients were evaluated for response.

Arm/Group Title	Chloroquine With Taxane or Taxane-Like (Paclitaxel, Docetaxel, Abraxane, Ixabepilone) Chemotherapy
Arm/Group Description	Chloroquine (250 mg) was given daily orally with either Paclitaxel or Docetaxel or Abraxane or Ixabepilone chemotherapy every 3 weeks (1 cycle) for a maximum of 6 cycles. Paclitaxel: Chloroquine 250mg po daily together with Paclitaxel (Taxane) 175 mg/m2 three hours infusion every three weeks. Docetaxel: Chloroquine 250mg po daily together with docetaxel 75 mg/m2 administered intravenously over one hour every three weeks Abraxane: Chloroquine 250mg po daily together with Abraxane 260 mg/m2 administered intravenously over 30 minutes every three weeks. Ixabepilone: Chloroquine 250mg po daily together with Ixabepilone is 40 mg/m2 administered intravenously over three hours every three weeks.
Period Title: Overall Study
STARTED	38
COMPLETED	31
NOT COMPLETED	7

Baseline Characteristics

Arm/Group Title	Chloroquine With Taxane or Taxane-Like (Paclitaxel, Docetaxel, Abraxane, Ixabepilone) Chemotherapy
Arm/Group Description	Chloroquine (250 mg) was given daily orally with either Paclitaxel or Docetaxel or Abraxane or Ixabepilone chemotherapy every 3 weeks (1 cycle) for a maximum of 6 cycles. Paclitaxel: Chloroquine 250mg po daily together with Paclitaxel (Taxane) 175 mg/m2 three hours infusion every three weeks. Docetaxel: Chloroquine 250mg po daily together with docetaxel 75 mg/m2 administered intravenously over one hour every three weeks Abraxane: Chloroquine 250mg po daily together with Abraxane 260 mg/m2 administered intravenously over 30 minutes every three weeks. Ixabepilone: Chloroquine 250mg po daily together with Ixabepilone is 40 mg/m2 administered intravenously over three hours every three weeks.
Overall Participants	38
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	54.1
Sex: Female, Male (Count of Participants)
Female	38 100%
Male	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	5 13.2%
Not Hispanic or Latino	33 86.8%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	3 7.9%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	6 15.8%
White	29 76.3%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United States	38 100%
Metastatic breast cancer (Count of Participants)
Count of Participants [Participants]	23 60.5%
Locally advanced breast cancer (Count of Participants)
Count of Participants [Participants]	15 39.5%
HR+ HEGFR- breast cancer (Count of Participants)
Count of Participants [Participants]	20 52.6%
Triple Negative Breast Cancer (Count of Participants)
Count of Participants [Participants]	18 47.4%

Outcome Measures

1. Primary Outcome

Title	Overall Response Rate (ORR)
Description	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Chloroquine With Taxane or Taxane-Like (Paclitaxel, Docetaxel, Abraxane, Ixabepilone) Chemotherapy
Arm/Group Description	Chloroquine (250 mg) was given daily orally with either Paclitaxel or Docetaxel or Abraxane or Ixabepilone chemotherapy every 3 weeks (1 cycle) for a maximum of 6 cycles. Paclitaxel: Chloroquine 250mg po daily together with Paclitaxel (Taxane) 175 mg/m2 three hours infusion every three weeks. Docetaxel: Chloroquine 250mg po daily together with docetaxel 75 mg/m2 administered intravenously over one hour every three weeks Abraxane: Chloroquine 250mg po daily together with Abraxane 260 mg/m2 administered intravenously over 30 minutes every three weeks. Ixabepilone: Chloroquine 250mg po daily together with Ixabepilone is 40 mg/m2 administered intravenously over three hours every three weeks.
Measure Participants	31
Number (95% Confidence Interval) [percentage of participants]	45.16 118.8%

2. Secondary Outcome

Title	Time to Progression Free Survival (PFS)
Description	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Chloroquine With Taxane or Taxane-Like (Paclitaxel, Docetaxel, Abraxane, Ixabepilone) Chemotherapy
Arm/Group Description	Chloroquine (250 mg) was given daily orally with either Paclitaxel or Docetaxel or Abraxane or Ixabepilone chemotherapy every 3 weeks (1 cycle) for a maximum of 6 cycles. Paclitaxel: Chloroquine 250mg po daily together with Paclitaxel (Taxane) 175 mg/m2 three hours infusion every three weeks. Docetaxel: Chloroquine 250mg po daily together with docetaxel 75 mg/m2 administered intravenously over one hour every three weeks Abraxane: Chloroquine 250mg po daily together with Abraxane 260 mg/m2 administered intravenously over 30 minutes every three weeks. Ixabepilone: Chloroquine 250mg po daily together with Ixabepilone is 40 mg/m2 administered intravenously over three hours every three weeks.
Measure Participants	31
Median (95% Confidence Interval) [months]	12.4

3. Secondary Outcome

Title	Time of Overall Survival (OS)
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Chloroquine With Taxane or Taxane-Like (Paclitaxel, Docetaxel, Abraxane, Ixabepilone) Chemotherapy
Arm/Group Description	Chloroquine (250 mg) was given daily orally with either Paclitaxel or Docetaxel or Abraxane or Ixabepilone chemotherapy every 3 weeks (1 cycle) for a maximum of 6 cycles. Paclitaxel: Chloroquine 250mg po daily together with Paclitaxel (Taxane) 175 mg/m2 three hours infusion every three weeks. Docetaxel: Chloroquine 250mg po daily together with docetaxel 75 mg/m2 administered intravenously over one hour every three weeks Abraxane: Chloroquine 250mg po daily together with Abraxane 260 mg/m2 administered intravenously over 30 minutes every three weeks. Ixabepilone: Chloroquine 250mg po daily together with Ixabepilone is 40 mg/m2 administered intravenously over three hours every three weeks.
Measure Participants	31
Median (95% Confidence Interval) [months]	25.4

4. Secondary Outcome

Title	Number of Patients Who Experienced Grade 3 of Greater Adverse Events
Description	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Chloroquine With Taxane or Taxane-Like (Paclitaxel, Docetaxel, Abraxane, Ixabepilone) Chemotherapy
Arm/Group Description	Chloroquine (250 mg) was given daily orally with either Paclitaxel or Docetaxel or Abraxane or Ixabepilone chemotherapy every 3 weeks (1 cycle) for a maximum of 6 cycles. Paclitaxel: Chloroquine 250mg po daily together with Paclitaxel (Taxane) 175 mg/m2 three hours infusion every three weeks. Docetaxel: Chloroquine 250mg po daily together with docetaxel 75 mg/m2 administered intravenously over one hour every three weeks Abraxane: Chloroquine 250mg po daily together with Abraxane 260 mg/m2 administered intravenously over 30 minutes every three weeks. Ixabepilone: Chloroquine 250mg po daily together with Ixabepilone is 40 mg/m2 administered intravenously over three hours every three weeks.
Measure Participants	31
Count of Participants [Participants]	4 10.5%

Adverse Events

Time Frame	Serious Adverse Events and Other (Not Including Serious) Adverse Events were assessed from time of informed consent up to 30 months. All-Cause Mortality was assessed up to 85 months and reported at a median follow-up of 25.36 months.
Arm/Group Title	Chloroquine With Taxane or Taxane-Like (Paclitaxel, Docetaxel, Abraxane, Ixabepilone) Chemotherapy
Arm/Group Description	Chloroquine (250 mg) was given daily orally with either Paclitaxel or Docetaxel or Abraxane or Ixabepilone chemotherapy every 3 weeks (1 cycle) for a maximum of 6 cycles. Paclitaxel: Chloroquine 250mg po daily together with Paclitaxel (Taxane) 175 mg/m2 three hours infusion every three weeks. Docetaxel: Chloroquine 250mg po daily together with docetaxel 75 mg/m2 administered intravenously over one hour every three weeks Abraxane: Chloroquine 250mg po daily together with Abraxane 260 mg/m2 administered intravenously over 30 minutes every three weeks. Ixabepilone: Chloroquine 250mg po daily together with Ixabepilone is 40 mg/m2 administered intravenously over three hours every three weeks.
All Cause Mortality
	Chloroquine With Taxane or Taxane-Like (Paclitaxel, Docetaxel, Abraxane, Ixabepilone) Chemotherapy
	Affected / at Risk (%)	# Events
Total	21/31 (67.7%)
Serious Adverse Events
	Chloroquine With Taxane or Taxane-Like (Paclitaxel, Docetaxel, Abraxane, Ixabepilone) Chemotherapy
	Affected / at Risk (%)	# Events
Total	1/38 (2.6%)
Blood and lymphatic system disorders
Neutropenia	1/38 (2.6%)
Other (Not Including Serious) Adverse Events
	Chloroquine With Taxane or Taxane-Like (Paclitaxel, Docetaxel, Abraxane, Ixabepilone) Chemotherapy
	Affected / at Risk (%)	# Events
Total	9/38 (23.7%)
Blood and lymphatic system disorders
Thrombocytopenia	1/38 (2.6%)
Gastrointestinal disorders
Diarrhea	1/38 (2.6%)
General disorders
Back pain	1/38 (2.6%)
Dehydration	1/38 (2.6%)
Fatigue	2/38 (5.3%)
Infusion reaction	1/38 (2.6%)
Syncope	1/38 (2.6%)
Hand-foot syndrome	1/38 (2.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.