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:||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|
- Tumor Response Rate [ Time Frame: 3 years ] [ Designated as safety issue: No ]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.
- Duration of Response [ Time Frame: 5 years ] [ Designated as safety issue: No ]
- Time to Progressive Disease [ Time Frame: 5 years ] [ Designated as safety issue: No ]
- Survival Time [ Time Frame: 5 years ] [ Designated as safety issue: No ]
- Pharmacodynamic Markers for Autophagy Detection [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- Effects of Hydroxychloroquine on Autophagy [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- Correlation of Estrogen Receptor, Progesterone Receptor and/or HER2 Status With Treatment Response [ Time Frame: 5 years ] [ Designated as safety issue: No ]
|Study Start Date:||February 2009|
|Study Completion Date:||December 2011|
|Primary Completion Date:||December 2011 (Final data collection date for primary outcome measure)|
|Experimental: Ixabepilone and hydroxychloroquine||
Dose escalation from 200 mg po qd to 200 mg po bid.Drug: ixabepilone
Starting dose of 40 mg/m2 and can dose reduce to 32 mg/m2.
- 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)
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00765765
|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||Rutgers Cancer Institute of New Jersey|