Sunitinib, Cyclophosphamide, and Methotrexate in Treating Patients With Metastatic Breast Cancer - Full Text View

Sponsors and Collaborators:	UCSF Helen Diller Family Comprehensive Cancer Center National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00616122

Purpose

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.

Condition	Intervention	Phase
Breast Cancer	Drug: cyclophosphamide Drug: methotrexate Drug: sunitinib malate Other: laboratory biomarker analysis	Phase I Phase II

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer

Drug Information available for: Cyclophosphamide Methotrexate Sunitinib malate Sunitinib

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label
Official Title:	Phase I/II Study of SU11248 (Sutent) in Combination With Metronomic Dosing of Cyclophosphamide and Methotrexate in Patients With Metastatic Breast Cancer

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Maximum tolerated dose (Phase I) [ Designated as safety issue: Yes ]
Time to disease progression (Phase II) [ Designated as safety issue: No ]

Secondary Outcome Measures:

Response rate [ Designated as safety issue: No ]
Duration of response [ Designated as safety issue: No ]
Toxicity [ Designated as safety issue: Yes ]
Feasibility [ Designated as safety issue: Yes ]
Correlation of outcome measures with possible surrogate markers including serial measurements of circulating tumor cells and circulating endothelial cells [ Designated as safety issue: No ]

Estimated Enrollment:	56
Study Start Date:	March 2006
Estimated Primary Completion Date:	December 2009 (Final data collection date for primary outcome measure)

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 VEGF levels.

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

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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
ECOG performance status 0-2
Life expectancy ≥ 12 weeks
ANC ≥ 1,000/mm³
Platelet count ≥ 100,000/mm³
Creatinine ≤ 1.5 times upper limit of normal (ULN)
AST and 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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00616122

Locations

United States, California
UCSF Helen Diller Family Comprehensive Cancer Center	Recruiting
San Francisco, California, United States, 94115
Contact: Clinical Trials Office - UCSF Helen Diller Family Comprehensi 877-827-3222

Sponsors and Collaborators

UCSF Helen Diller Family Comprehensive Cancer Center

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Hope S. Rugo, MD

UCSF Helen Diller Family Comprehensive Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000583268, UCSF-057519
Study First Received:	February 14, 2008
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00616122 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

recurrent breast cancer
stage IV breast cancer
male breast cancer

Study placed in the following topic categories:

Antimetabolites
Skin Diseases
Immunologic Factors
Breast Neoplasms
Breast Cancer, Male
Cyclophosphamide
Folic Acid Antagonists
Angiogenesis Inhibitors
Immunosuppressive Agents

Recurrence
Folic Acid
Breast Neoplasms, Male
Sunitinib
Methotrexate
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Alkylating Agents
Breast Diseases

Additional relevant MeSH terms:

Antimetabolites
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Cyclophosphamide
Reproductive Control Agents
Neoplasms by Site
Sunitinib
Therapeutic Uses
Abortifacient Agents
Methotrexate
Growth Inhibitors
Angiogenesis Modulating Agents

Alkylating Agents
Dermatologic Agents
Nucleic Acid Synthesis Inhibitors
Breast Diseases
Skin Diseases
Growth Substances
Breast Neoplasms
Enzyme Inhibitors
Folic Acid Antagonists
Abortifacient Agents, Nonsteroidal
Angiogenesis Inhibitors
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Myeloablative Agonists

ClinicalTrials.gov processed this record on May 07, 2009