Clinical trial NCT00616122
Conditions: Breast Cancer
Keywords: recurrent breast cancer stage IV breast cancer male breast cancer
Sponsor: University of California, San Francisco
Start date: 2006-03-01; Completion date: 2012-12-01
Enrollment: 32 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
RATIONALE: Sunitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cyclophosphamide and methotrexate, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving sunitinib together with combination chemotherapy may kill more tumor cells.

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

Detailed description:
OBJECTIVES:

Primary

* To determine the maximum tolerated dose of the combination of metronomic dose cyclophosphamide and methotrexate with continuous dosing sunitinib malate. (Phase I)
* To determine the time to disease progression in patients with metastatic breast cancer treated with metronomic dose chemotherapy with cyclophosphamide and methotrexate combined with continuous dosing of sunitinib malate. (Phase II)

Secondary

* To determine the response rate in patients receiving this treatment.
* To determine the duration of response in patients receiving this treatment.
* To determine the toxicity of this regimen in these patients.
* To determine the feasibility by assessment of toxicities of this regimen and number of voluntary withdrawals from the study.
* To correlate outcome measures with possible surrogate markers including serial measurements of circulating tumor cells and circulating endothelial cells.

OUTLINE: This is a dose-escalation study of sunitinib malate.

* Phase I: Patients receive oral sunitinib malate once daily. Beginning 14 days later, patients also receive oral cyclophosphamide once daily on days 1-21 and oral methotrexate twice daily on days 1, 2, 8, 9, 15, and 16. Treatment with sunitinib malate, cyclophosphamide, and methotrexate repeats every 21 days\* in the absence of disease progression or unacceptable toxicity.
* Phase II: Patients receive sunitinib malate at the maximum tolerated dose determined in phase I and cyclophosphamide and methotrexate as in phase I.

NOTE: \*Course 1 includes 2 weeks of sunitinib malate alone followed by sunitinib malate, cyclophosphamide, and methotrexate for 21 days

Blood samples are collected periodically for measurement of circulating tumor cells, circulating endothelial cells, and vascular endothelial growth factor (VEGF) levels.

After completion of study treatment, patients are followed for 30 days and then every 2 months for 1 year.

Arms: arm 1: None
Interventions: intervention 1: cyclophosphamide intervention 2: methotrexate intervention 3: sunitinib malate intervention 4: laboratory biomarker analysis
Intervention descriptions: intervention 1: None intervention 2: None intervention 3: None intervention 4: None

Protocol documents: