SU5416 and Doxorubicin in Treating Patients With Stage IIIB or Stage IV Inflammatory Breast Cancer - Full Text View

Sponsor:	Case Comprehensive Cancer Center
Collaborator:	National Cancer Institute (NCI)
Information provided by:	Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier:	NCT00005822

Purpose

RATIONALE: SU5416 may stop the growth of breast cancer by stopping blood flow to the tumor. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining SU5416 with chemotherapy may kill more cancer cells.

PURPOSE: Phase I trial to study the effectiveness of combining SU5416 and doxorubicin in treating patients who have stage IIIB or stage IV inflammatory breast cancer.

Condition	Intervention	Phase
Breast Cancer	Drug: doxorubicin hydrochloride Drug: semaxanib Procedure: conventional surgery Radiation: radiation therapy Drug: tamoxifen	Phase I

Study Type:	Interventional
Study Design:	Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase I Pharmacokinetic, Pharmacodynamic, and Clinical Study of the Combination of the Angiogenesis Inhibitor SU5416 and Doxorubicin in Inflammatory Breast Cancer

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer

Drug Information available for: Tamoxifen Doxorubicin Doxorubicin hydrochloride Tamoxifen citrate Semaxanib SU 5416

U.S. FDA Resources

Further study details as provided by Case Comprehensive Cancer Center:

Primary Outcome Measures:

Determine the maximum tolerated dose of SU5416 and doxorubicin in patients with stage IIIB or IV inflammatory breast cancer. [ Time Frame: Treatment repeats every 21 days for 5 courses in the absence of disease progression or unacceptable toxicity. ] [ Designated as safety issue: Yes ]

Enrollment:	21
Study Start Date:	April 2000
Study Completion Date:	October 2003
Primary Completion Date:	December 2002 (Final data collection date for primary outcome measure)

Intervention Details:

Patients receive doxorubicin IV continuously over 72 hours on days 1-3 of course 1. For all subsequent courses, patients receive doxorubicin as in course 1. Treatment repeats every 21 days for 5 courses in the absence of disease progression or unacceptable toxicity.

For all subsequent courses, after course 1 patients SU5416 IV over 1 hour twice weekly (on days 1 and 4) beginning on week 2 of course 2. Treatment repeats every 21 days for 5 courses in the absence of disease progression or unacceptable toxicity.

Other Name: SU5416

Patients undergo a modified radical mastectomy.

Patients undergo radiotherapy to the chest wall and regional lymph nodes.

Patients with estrogen or progesterone receptor positive disease receive oral tamoxifen for 5 years after radiotherapy.

Detailed Description:

OBJECTIVES:

Determine the maximum tolerated dose of SU5416 and doxorubicin in patients with stage IIIB or IV inflammatory breast cancer.
Determine the overall response, response rate, and progression-free survival rate of patients treated with this regimen.
Determine the antiangiogenic effects of this regimen in these patients.
Assess the relationship of plasma levels of these drugs with safety and efficacy in these patients.

OUTLINE: This is a dose-escalation study.

Patients receive doxorubicin IV continuously over 72 hours on days 1-3 of course 1. For all subsequent courses, patients receive doxorubicin as in course 1 and SU5416 IV over 1 hour twice weekly (on days 1 and 4) beginning on week 2 of course 2. Treatment repeats every 21 days for 5 courses in the absence of disease progression or unacceptable toxicity. After chemotherapy, all patients undergo a modified radical mastectomy and radiotherapy to the chest wall and regional lymph nodes. Patients with estrogen or progesterone receptor positive disease receive oral tamoxifen for 5 years after radiotherapy.

Cohorts of 3-6 patients receive escalating doses of SU5416 and doxorubicin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, an additional 3 patients may be treated at that dose level.

Patients are followed every 3 months until disease progression.

PROJECTED ACCRUAL: A total of 15-30 patients will be accrued for this study within 6-9 months.

Eligibility

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

Criteria

DISEASE CHARACTERISTICS:

Histologically or cytologically confirmed stage IIIB or IV (supraclavicular lymph node involvement or metastasis) inflammatory breast cancer
- Primary or secondary
No brain metastases or primary brain tumors
Hormone receptor status:
- Not specified

PATIENT CHARACTERISTICS:

Age:

18 and over

Sex:

Male or female

Menopausal status:

Not specified

Performance status:

ECOG 0-2

Life expectancy:

At least 12 weeks

Hematopoietic:

WBC at least 3,500/mm^3
Granulocyte count at least 1,500/mm^3
Platelet count at least 100,000/mm^3
Hemoglobin greater than 9.0 g/dL

Hepatic:

Bilirubin normal
AST and ALT less than 2 times upper limit of normal
PT and PTT normal OR
INR less than 1.1

Renal:

Creatinine less than 1.5 mg/dL OR
Creatinine clearance greater than 60 mL/min

Cardiovascular:

LVEF at least 50% by MUGA
No New York Heart Association class III or IV heart disease
No uncompensated coronary artery disease
No myocardial infarction or unstable angina within the past 6 months
No deep venous or arterial thrombosis within the past 3 months

Pulmonary:

No history of pulmonary embolism within the past 3 months

Other:

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No history of diabetes mellitus with severe peripheral vascular disease
No other prior or concurrent malignancies within the past 10 years except inactive nonmelanomatous skin cancer or carcinoma in situ of the cervix
No other uncontrolled illnesses

PRIOR CONCURRENT THERAPY:

Biologic therapy:

No concurrent epoetin alfa or filgrastim (G-CSF)

Chemotherapy:

No more than 2 prior chemotherapy regimens allowed
No prior doxorubicin or other anthracycline

Endocrine therapy:

Not specified

Radiotherapy:

Prior radiotherapy allowed

Surgery:

Not specified

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00005822

Locations

United States, Ohio
Ireland Cancer Center at University Hospitals Case Medical Center
Cleveland, Ohio, United States, 44106-5065

Sponsors and Collaborators

Case Comprehensive Cancer Center

National Cancer Institute (NCI)

Investigators

Study Chair:

Beth A. Overmoyer, MD, FACP

Ireland Cancer Center at University Hospitals Case Medical Center, Case 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

Responsible Party:	Beth A. Overmoyer, MD, Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier:	NCT00005822 History of Changes
Other Study ID Numbers:	CWRU5199, U01CA062502, P30CA043703, CWRU-5199, NCI-T99-0099
Study First Received:	June 2, 2000
Last Updated:	June 10, 2010
Health Authority:	United States: Federal Government

Keywords provided by Case Comprehensive Cancer Center:

stage IV breast cancer
recurrent breast cancer
stage IIIB breast cancer
inflammatory breast cancer
male breast cancer

Additional relevant MeSH terms:

Breast Neoplasms
Inflammatory Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Doxorubicin
SU 5416
Tamoxifen
Angiogenesis Inhibitors
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

Antineoplastic Agents, Hormonal
Selective Estrogen Receptor Modulators
Estrogen Receptor Modulators
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Bone Density Conservation Agents
Estrogen Antagonists
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on February 09, 2012