PTK787 + Trastuzumab for HER2 Overexpressing Metastatic Breast Cancer

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

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.

Study Overview

• Status: Terminated
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: PTK787; Drug: Trastuzumab

Detailed 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 Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Elkhart, Indiana, United States, 46515
      • Elkhart Clinic
    • Fort Wayne, Indiana, United States, 46815
      • Fort Wayne Oncology & Hematology, Inc
    • Goshen, Indiana, United States, 46527
      • Center for Cancer Care at Goshen Health System
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Cancer Center
    • Lafayette, Indiana, United States, 47904
      • Arnett Cancer Care
    • Muncie, Indiana, United States, 47303
      • Medical Consultants, P.C.
    • South Bend, Indiana, United States, 46601
      • Northern Indiana Cancer Research Consortium
    • Terre Haute, Indiana, United States, 47804
      • AP&S Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Histologic or cytologic diagnosis of breast cancer with evidence of measurable (1) unresectable, locally recurrent, or (2) metastatic disease. Locally recurrent disease must not be amenable to resection OR radiation with curative intent.
• Patient's disease may not involve more than 3 metastatic sites. In addition, patient may not be symptomatic from pulmonary metastasis or have liver metastasis involving > 50% of parenchyma.
• HER2 gene amplification by FISH. HER protein overexpression by immunohistochemistry will not be sufficient for entry.
• Negative pregnancy test

Exclusion Criteria:

• No prior cytotoxic chemotherapy or trastuzumab for locally recurrent or metastatic disease.
• No prior treatment with any VEGF inhibiting agents
• No history or presence of central nervous system (CNS) disease.
• No other forms of cancer therapy including radiation, chemotherapy and hormonal therapy within 21 days prior to being registered for protocol therapy.
• No major surgery within 28 days prior to being registered for protocol therapy.
• No uncontrolled hypertension (SBP > 170, DBP > 90), history of labile hypertension or history of poor compliance with antihypertensive therapy.
• No requirement for therapeutic anticoagulation, regular aspirin (> 325 mg/day) or NSAID use.
• No current breast feeding.
• No impairment of gastrointestinal (GI) function that may significantly alter the absorption of PTK787.
• No evidence of other serious concomitant systemic disorders incompatible with the study (at the discretion of the investigator).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single Group Assignment; Trastuzumab + PTK787 for HER2 positive patients	Drug: PTK787; PTK787 daily; Drug: Trastuzumab; Trastuzumab 4 mg/kg IV week 1, followed by 2 mg/kg weekly with disease evaluation every other cycle*

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Phase I Cohorts:	18 months
The primary objective is to ensure the safety and tolerability of the combination of Trastuzumab and PTK787,	18 months
Phase II Cohorts:	18 months
To assess response rate of PTK787 combined with trastuzumab in patients with newly diagnosed HER2 overexpressing	18 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Phase II Cohorts:	12 months
To assess the safety and tolerability of PTK787 combined with trastuzumab	12 months
To assess the time to progression and clinical benefit of PTK787 combined with trastuzumab	12 months

Collaborators and Investigators

• Sponsor: Hoosier Cancer Research Network
• Collaborators: Novartis Pharmaceuticals; Walther Cancer Institute

Publications and helpful links

Helpful Links

• Hoosier Oncology Group Home Page

Study record dates

Study Major Dates

• Study Start: January 1, 2005
• Primary Completion (Actual): August 1, 2006
• Study Completion (Actual): August 1, 2006

Study Registration Dates

• First Submitted: September 12, 2005
• First Submitted That Met QC Criteria: September 14, 2005
• First Posted (Estimate): September 22, 2005

Study Record Updates

• Last Update Posted (Estimate): December 9, 2015
• Last Update Submitted That Met QC Criteria: December 8, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: Breast Cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Immunological; Protein Kinase Inhibitors; Trastuzumab; Vatalanib
• Other Study ID Numbers: HOG BRE04-80