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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00216047
• Other study ID #: HOG BRE04-80
• Status: Terminated
• Phase: Phase 1/Phase 2
• First received: September 12, 2005
• Last updated: December 8, 2015
• Start date: January 2005
• Est. completion date: August 2006

Study information

• Verified date: December 2015
• Source: Hoosier Cancer Research Network
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

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.

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 7
• Est. completion date: August 2006
• Est. primary completion date: August 2006
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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 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

Intervention

Drug:
• PTK787
PTK787 daily
• Trastuzumab
Trastuzumab 4 mg/kg IV week 1, followed by 2 mg/kg weekly with disease evaluation every other cycle*

Locations

Country	Name	City	State
United States	Elkhart Clinic	Elkhart	Indiana
United States	Fort Wayne Oncology & Hematology, Inc	Fort Wayne	Indiana
United States	Center for Cancer Care at Goshen Health System	Goshen	Indiana
United States	Indiana University Cancer Center	Indianapolis	Indiana
United States	Arnett Cancer Care	Lafayette	Indiana
United States	Medical Consultants, P.C.	Muncie	Indiana
United States	Northern Indiana Cancer Research Consortium	South Bend	Indiana
United States	AP&S Clinic	Terre Haute	Indiana

Sponsors (3)

Lead Sponsor	Collaborator
Hoosier Cancer Research Network	Novartis Pharmaceuticals, Walther Cancer Institute

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase I Cohorts:		18 months	Yes
Primary	The primary objective is to ensure the safety and tolerability of the combination of Trastuzumab and PTK787,		18 months	Yes
Primary	Phase II Cohorts:		18 months	No
Primary	To assess response rate of PTK787 combined with trastuzumab in patients with newly diagnosed HER2 overexpressing		18 months	No
Secondary	Phase II Cohorts:		12 months	Yes
Secondary	To assess the safety and tolerability of PTK787 combined with trastuzumab		12 months	Yes
Secondary	To assess the time to progression and clinical benefit of PTK787 combined with trastuzumab		12 months	No

External Links

•   Hoosier Oncology Group Home Page