PTK787 + Trastuzumab for HER2 Overexpressing Metastatic Breast Cancer

NCT00216047 | Terminated Phase 1 DMC

• 1 other identifier: HOG BRE04-80
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 8

Brief 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.

Conditions

Breast Cancer

Keywords

Breast Cancer

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (3)

• 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

Study Arms (1)

Single Group Assignment

EXPERIMENTAL

Trastuzumab + PTK787 for HER2 positive patients

Drug: PTK787; Drug: Trastuzumab

Interventions

PTK787 DRUG

PTK787 daily

Single Group Assignment

Trastuzumab DRUG

Trastuzumab 4 mg/kg IV week 1, followed by 2 mg/kg weekly with disease evaluation every other cycle\*

Single Group Assignment

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Hoosier Cancer Research Network: lead
• Novartis Pharmaceuticals: collaborator
• Walther Cancer Institute: collaborator

Study Sites (8)

Elkhart Clinic

Elkhart, Indiana, 46515, United States

Location

Fort Wayne Oncology & Hematology, Inc

Fort Wayne, Indiana, 46815, United States

Location

Center for Cancer Care at Goshen Health System

Goshen, Indiana, 46527, United States

Location

Indiana University Cancer Center

Indianapolis, Indiana, 46202, United States

Location

Arnett Cancer Care

Lafayette, Indiana, 47904, United States

Location

Medical Consultants, P.C.

Muncie, Indiana, 47303, United States

Location

Northern Indiana Cancer Research Consortium

South Bend, Indiana, 46601, United States

Location

AP&S Clinic

Terre Haute, Indiana, 47804, United States

Location

Related Links

• Hoosier Oncology Group Home Page

MeSH Terms

Conditions

Breast Neoplasms

Interventions

vatalanib; Trastuzumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Kathy Miller, M.D.

  Hoosier Oncology Group, LLC

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, IU School of Medicine

Study Record Dates

• First Submitted: September 12, 2005
• First Posted: September 22, 2005
• Study Start: January 1, 2005
• Primary Completion: August 1, 2006
• Study Completion: August 1, 2006
• Last Updated: December 9, 2015

Record last verified: 2015-12

Locations

US (8)