Phase I Study of Aprotinin in Advanced Breast Cancer

NCT00354900 | Terminated Phase 1 DMC

• 1 other identifier: D-0540
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

There is an intimate relationship between processes which promote growth, invasion, and metastasis of cancers, and processes which regulate blood clotting. The enzymes uPA and PAI-1 are key regulators of the remodeling of recently formed blood clots, and there is substantial information linking greater levels of uPA and PAI-1 in breast cancers with a greater likelihood of breast cancer recurrence and death. As uPA and PAI-1 are excellent markers for a cancer's aggressive clinical behavior, uPA and PAI-1 may be potential targets for anticancer therapy. Aprotinin is an inhibitor of uPA activation, and has been approved by the FDA to reduce blood loss in patients undergoing cardiopulmonary bypass surgery. Studies in animals and limited studies in patients have shown that Aprotinin slows the growth of tumors. Our hypothesis is that uPA is chronically activated in malignancies, and that inhibition of uPA by Aprotinin would slow the rate of progression of breast cancer.

Conditions

Metastatic Breast Cancer

Keywords

breast cancer; fibrinolysis; urokinase-type plasminogen activator; plasminogen activator inhibitor; aprotinin; plasmin/alpha-2-antiplasmin complex

Outcome Measures

Primary Outcomes (1)

• To determine the maximum tolerated single dose of Aprotinin in patients with advanced breast cancer

Secondary Outcomes (3)

• To determine the toxicities of a single infusion of Aprotinin in patients with advanced breast cancer

• To determine the progression free survival and overall survival following a single dose of Aprotinin in patients with advanced breast cancer

• To determine the effects of a single dose of Aprotinin on markers of the coagulation pathway

Interventions

Aprotinin DRUG

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with a histologically or cytologically proven metastatic breast cancer.
• Patients with at least one bidimensionally measurable lesion (diameter \> 1 cm), or an evaluable bone lesion that will not undergo biopsy.
• Age \> 18 years.
• Life expectancy of at least 6 months.
• ECOG performance status 0-3.
• Screening laboratories within the following parameters: ANC \> 1500 cells/mm3, Platelets \> 100,000 cells/mm3, AST \< 2 x upper limit of normal, Bilirubin \< 1.5 x upper limit of normal, Calculated creatinine clearance \> 30 cc/min by the Cockroft and Gault equation.
• Concurrent treatment with hormonal therapy or trastuzumab is allowed.
• Patients must be post-menopausal (either as a result of surgery, or amenorrhea for at least 12 consecutive months), or they must be practicing either abstinence, an adequate method of contraception (intrauterine device or barrier contraception), or their sexual partner must be sterile. Women who are pregnant, breast-feeding, or who are fertile and not practicing an adequate means of contraception will be excluded.
• Patients must have a central venous catheter.
• Patients must be able to give informed consent indicating that they are aware of the investigational nature of this study.

You may not qualify if:

• No known CNS metastases.
• No treatment with cytotoxic chemotherapy allowed within 21 days of treatment with Aprotinin.
• No treatment with investigational agents allowed within 21 days of treatment with Aprotinin.
• No severe cardiovascular disease including unstable heart rhythm, uncompensated congestive heart failure, unstable angina or myocardial infarction within 6 months.
• No bleeding diathesis or coagulopathy including concomitant use of anticoagulants for thromboembolic disease
• No active anticoagulant therapy (including antiplatelet agents) for at least ten days.
• No active, uncontrolled bacterial, viral or fungal infection.
• No patients who are known or expected to be allergic to aprotinin, or who have received prior aprotinin.
• No patient with chronic systolic blood pressure (SBP) \< 90 mm Hg. If the (SBP) is \< 90 mm Hg on the day of treatment intravenous fluid may be administered to restore intravascular volume, if clinically indicated. In such case, if IV fluid corrects the SBP then the study drug may be given

Sponsors & Collaborators

• Dartmouth-Hitchcock Medical Center: lead

Study Sites (1)

Norris Cotton Cancer Center - Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Aprotinin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Proteins; Amino Acids, Peptides, and Proteins

Study Officials

• Gary N Schwartz, MD

  Norris Cotton Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: July 18, 2006
• First Posted: July 20, 2006
• Study Start: July 1, 2006
• Study Completion: April 1, 2007
• Last Updated: August 4, 2009

Record last verified: 2009-08

Locations

US (1)