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Ixabepilone and Hydroxychloroquine in Treating Patients With Metastatic Breast Cancer

Phase 1
Terminated
Conditions
Breast Cancer
Interventions
Registration Number
NCT00765765
Lead Sponsor
University of Medicine and Dentistry of New Jersey
Brief Summary

RATIONALE: Drugs used in chemotherapy, such as ixabepilone, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Hydroxychloroquine may help ixabepilone work better by making tumor cells more sensitive to the drug.

PURPOSE: This phase I/II trial is studying the side effects and best dose of ixabepilone given together with hydroxychloroquine and to see how well they work in treating patients with metastatic breast cancer.

Detailed Description

OBJECTIVES:

* The primary objective of this study is to assess the antitumor activity, measured by tumor response rate, in patients who receive this regimen as a third-line treatment. (Phase II)

Secondary

* To measure the duration of response for responding patients.

* To measure the time to progressive disease.

* To measure survival time.

* To characterize the quantitative and qualitative toxicities of this regimen in these patients.

* To develop pharmacodynamic markers for autophagy detection in patient specimens.

* To characterize the effects of hydroxychloroquine on autophagy in patients in vivo.

* To investigate whether the estrogen receptor, progesterone receptor, and/or HER2 status of breast tumors correlates with treatment response.

OUTLINE: This is a multicenter, phase I dose-escalation study of ixabepilone followed by a phase II study.

During the first course, patients receive ixabepilone IV over 3 hours on day 1 and oral hydroxychloroquine twice daily on days 3-21. On all subsequent courses, patients receive ixabepilone IV over 3 hours on day 1 and oral hydroxychloroquine twice daily on days 1-21. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed every 6 months.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
6
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Ixabepilone and hydroxychloroquinehydroxychloroquine-
Ixabepilone and hydroxychloroquineixabepilone-
Primary Outcome Measures
NameTimeMethod
Tumor Response Rate3 years

Overall Complete Response and Partial Response will be considered tumor response. Ixabepilone as a single agent (40 mg/m2 as an intravenous infusion every 3 weeks) was evaluated in a previous (Phase II) study in women with metastatic breast cancer and that the objective tumor response rate was 11.5%. In another(Phase III) study, Ixabepilone in combination with capecitabine resulted in an objective tumor response rate of 35%, compared to that of capecitabine alone (14%). Therefore, in the Phase II portion of the ixabepilone plus hydroxychloroquine combination treatment study, a tumor response rate of less than 15% will be deemed uninteresting. The target tumor response rate will be 35%. Due to uncertainty about the true response rate of ixabepilone plus hydroxychloroquine combination on this patient poupation, we also will consider a response rate of 30% to be encouraging.

Secondary Outcome Measures
NameTimeMethod
Survival Time5 years
Pharmacodynamic Markers for Autophagy Detection2 years
Correlation of Estrogen Receptor, Progesterone Receptor and/or HER2 Status With Treatment Response5 years
Effects of Hydroxychloroquine on Autophagy2 years
Duration of Response5 years
Time to Progressive Disease5 years

Trial Locations

Locations (2)

Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School

🇺🇸

New Brunswick, New Jersey, United States

Cancer Institute of New Jersey at Hamilton

🇺🇸

Hamilton, New Jersey, United States

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