PTK787 + Trastuzumab for HER2 Overexpressing Metastatic Breast Cancer

Breast Cancer Clinical Trial

Official title: A Phase I/II Study of PTK787 in Combination With Trastuzumab in Patients With Newly Diagnosed HER2 Overexpressing Locally Recurrent or Metastatic Breast Cancer: Hoosier Oncology Group Trial BRE04-80

Status Terminated

Clinical Trial Summary

HER2 gene amplification increases VEGF production in breast cancers; combined inhibition of HER2 and VEGF enhances response in xenograft models. The upregulation of VEGF in HER2-overexpressing breast cancers may contribute to the aggressive phenotype observed in HER2-positive breast cancer. New therapeutics targeting VEGF and/or its receptors may enhance the efficacy of trastuzumab monotherapy.

This trial will investigate the safety and efficacy of combined HER2 and VEGF inhibition.

Clinical Trial Description

OUTLINE: This is a multi-center study.

PTK787 daily plus trastuzumab 4 mg/kg IV week 1, followed by 2 mg/kg weekly with disease evaluation every other cycle.

Patients may continue treatment until disease progression or toxicity intervenes.

Performance Status: ECOG 0 or 1

Life Expectancy: Not specified

Hematopoietic:

• ANC > 1500 mm3

• Platelets > 100,000 mm3

• Hemoglobin > 9 g/dL

• PTT and INR < 1.5 x ULN

Hepatic:

• ALT and AST < 3 x ULN (< 5 x ULN in patients with known liver metastases)

• Alkaline phosphatase < 2.5 x ULN

• Serum bilirubin < 1.5 x ULN

Renal:

• Serum creatinine < 1.5 x ULN

• Proteinuria < 1+ by dipstick OR total urinary protein < 500 mg/24 hours with measured creatinine clearance (CrCl) ≥ 50 mL/min

Cardiovascular:

• No clinically significant cardiac disease (e.g. congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmias not well controlled with medication) or myocardial infarction within the last 6 months.

• LVEF > LLN by MUGA or ECHO (obtained within 28 days prior to being registered for protocol therapy)

Pulmonary:

• Not specified ;

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

• NCT number: NCT00216047
• Study type: Interventional
• Source: Hoosier Cancer Research Network
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: January 2005
• Completion date: August 2006