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PTK787 + Trastuzumab for HER2 Overexpressing Metastatic Breast Cancer

This study has been terminated.
(Low patient enrollment; toxicities)
Sponsor:
ClinicalTrials.gov Identifier:
NCT00216047
First Posted: September 22, 2005
Last Update Posted: December 9, 2015
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
Novartis Pharmaceuticals
Walther Cancer Institute
Information provided by (Responsible Party):
Kathy Miller, MD, Hoosier Cancer Research Network
  Purpose

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.


Condition Intervention Phase
Breast Cancer Drug: PTK787 Drug: Trastuzumab Phase 1 Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Kathy Miller, MD, Hoosier Cancer Research Network:

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

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

Enrollment: 7
Study Start Date: January 2005
Study Completion Date: August 2006
Primary Completion Date: August 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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*

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
  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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).
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00216047


Locations
United States, Indiana
Elkhart Clinic
Elkhart, Indiana, United States, 46515
Fort Wayne Oncology & Hematology, Inc
Fort Wayne, Indiana, United States, 46815
Center for Cancer Care at Goshen Health System
Goshen, Indiana, United States, 46527
Indiana University Cancer Center
Indianapolis, Indiana, United States, 46202
Arnett Cancer Care
Lafayette, Indiana, United States, 47904
Medical Consultants, P.C.
Muncie, Indiana, United States, 47303
Northern Indiana Cancer Research Consortium
South Bend, Indiana, United States, 46601
AP&S Clinic
Terre Haute, Indiana, United States, 47804
Sponsors and Collaborators
Hoosier Cancer Research Network
Novartis Pharmaceuticals
Walther Cancer Institute
Investigators
Study Chair: Kathy Miller, M.D. Hoosier Oncology Group, LLC
  More Information

Additional Information:
Responsible Party: Kathy Miller, MD, Professor, IU School of Medicine, Hoosier Cancer Research Network
ClinicalTrials.gov Identifier: NCT00216047     History of Changes
Other Study ID Numbers: HOG BRE04-80
First Submitted: September 12, 2005
First Posted: September 22, 2005
Last Update Posted: December 9, 2015
Last Verified: December 2015

Keywords provided by Kathy Miller, MD, Hoosier Cancer Research Network:
Breast Cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Trastuzumab
Vatalanib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action