Ixabepilone and Hydroxychloroquine in Treating Patients With Metastatic Breast Cancer
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.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I/II Study of Ixabepilone in Combination With the Autophagy Inhibitor Hydroxychloroquine for the Treatment of Patients With Metastatic Breast Cancer|
- Recommended phase II dose of ixabepilone and hydroxychloroquine [ Time Frame: Phase I portion of study ] [ Designated as safety issue: Yes ]
- Duration of response [ Time Frame: Date of best response to date of progression ] [ Designated as safety issue: No ]
- Time to progressive disease [ Time Frame: Treatment start date to date of progression ] [ Designated as safety issue: No ]
- Survival time [ Time Frame: Treatment start date to date of death ] [ Designated as safety issue: Yes ]
- Toxicity [ Time Frame: Treatment start date to 30 days after end of treatment ] [ Designated as safety issue: Yes ]
- Pharmacodynamic markers for autophagy detection [ Time Frame: Cycle 1 ] [ Designated as safety issue: No ]
- Effects of hydroxychloroquine on autophagy [ Time Frame: cycle 1 ] [ Designated as safety issue: No ]
- Correlation of estrogen receptor, progesterone receptor and/or HER2 status with treatment response [ Time Frame: Baseline to date of best response ] [ Designated as safety issue: No ]
|Study Start Date:||February 2009|
|Study Completion Date:||March 2011|
|Primary Completion Date:||March 2011 (Final data collection date for primary outcome measure)|
- To determine the recommended phase II dose of ixabepilone and hydroxychloroquine in patients with metastatic breast cancer. (Phase I)
- To assess the antitumor activity, measured by tumor response rate, in patients who receive this regimen as a third-line treatment. (Phase II)
- 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.
|United States, New Jersey|
|Cancer Institute of New Jersey at Hamilton|
|Hamilton, New Jersey, United States, 08690|
|Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School|
|New Brunswick, New Jersey, United States, 08903|
|Principal Investigator:||Vassil Karantza-Wadsworth, MD||Cancer Institute of New Jersey|