PTK787 + Trastuzumab for HER2 Overexpressing Metastatic Breast Cancer - Full Text View

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:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: 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:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer

Drug Information available for: Trastuzumab

U.S. FDA Resources

Further study details as provided by Hoosier Oncology Group:

Primary Outcome Measures:

Phase I Cohorts: [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
The primary objective is to ensure the safety and tolerability of the combination of Trastuzumab and PTK787, [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
Phase II Cohorts: [ Time Frame: 18 months ] [ Designated as safety issue: No ]
To assess response rate of PTK787 combined with trastuzumab in patients with newly diagnosed HER2 overexpressing [ Time Frame: 18 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Phase II Cohorts: [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
To assess the safety and tolerability of PTK787 combined with trastuzumab [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
To assess the time to progression and clinical benefit of PTK787 combined with trastuzumab [ Time Frame: 12 months ] [ Designated as safety issue: No ]

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
Active Comparator: 1 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

Ages Eligible for Study:	18 Years and older
Genders 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

Please refer to this study by its ClinicalTrials.gov identifier: 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 Oncology Group

Novartis Pharmaceuticals

Walther Cancer Institute

Investigators

Study Chair:

Kathy Miller, M.D.

Hoosier Oncology Group, LLC

More Information

Additional Information:

Hoosier Oncology Group Home Page This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Kathy Miller, M.D., Hoosier Oncology Group
ClinicalTrials.gov Identifier:	NCT00216047 History of Changes
Other Study ID Numbers:	HOG BRE04-80
Study First Received:	September 12, 2005
Last Updated:	February 16, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by Hoosier Oncology Group:

Breast Cancer

Additional relevant MeSH terms:

Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Trastuzumab
Vatalanib

Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on June 18, 2013