Clinical trial NCT00616122: Sunitinib, Cyclophosphamide, and Methotrexate in Treating Patients With Metastatic Breast Cancer
Official title: Phase I/II Study of SU11248 (Sutent) in Combination With Metronomic Dosing of Cyclophosphamide and Methotrexate in Patients With Metastatic Breast Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Breast Cancer
Keywords: recurrent breast cancer
stage IV breast cancer
male breast cancer
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2008-02-15
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Pathologically confirmed diagnosis of breast cancer with documented progressive disease

  * Metastatic disease
* Measurable disease as defined by RECIST criteria or evaluable disease
* Must have received at least one prior chemotherapy regimen for metastatic breast cancer

  * Patients refusing all other chemotherapy for breast cancer may enroll without prior treatment
* Patients with HER2-overexpression disease must have been previously treated with trastuzumab (Herceptin®)
* Patients with stable brain metastases are eligible
* Hormone receptor status not specified

PATIENT CHARACTERISTICS:

* Menopausal status not specified
* Eastern Cooperative Oncology Group (ECOG) performance status 0-2
* Life expectancy ≥ 12 weeks
* Absolute Neutrophil Count (ANC) ≥ 1,000/mm³
* Platelet count ≥ 100,000/mm³
* Creatinine ≤ 1.5 times upper limit of normal (ULN)
* aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 times ULN (≤ 5 times ULN in the presence of liver metastases)
* Total bilirubin ≤ 1.5 times ULN
* Able to take oral medications and maintain hydration
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception during and for 6 months after treatment
* No severe concurrent illness including, but not limited to, any of the following:

  * Congestive heart failure
  * Significant cardiac disease
  * Uncontrolled hypertension
* Must be able to read and speak English

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* At least 2 weeks since prior treatment, including chemotherapy, hormonal therapy, trastuzumab (Herceptin®), or other targeted therapies
* Prior bevacizumab allowed if discontinued for any reason other than toxicity
* No potent inducers or inhibitors of CYP3A4 enzymes that effect the metabolism of sunitinib malate
* No prior sunitinib malate
* No other concurrent investigational therapy
* No concurrent radiotherapy
* Concurrent bisphosphonates allowed

Primary outcomes:
measure: Maximum Tolerated Dose of Sunitinib (Phase I)
timeFrame: 8 weeks
measure: Patients With Progression-free Survival (PFS) Greater Than or Equal to 12 Weeks (Phase II)
timeFrame: up to 12 weeks after treatment start date
Secondary outcomes:
measure: Overall Response Rate
timeFrame: until disease progression, up to 13 months post treatment
measure: Duration of Response
timeFrame: until disease progression up to 13 months post treatment
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
Study officials:
affiliation: University of California, San Francisco
name: Hope S. Rugo, MD
role: PRINCIPAL_INVESTIGATOR
References: