Clinical trial NCT00216047: PTK787 + Trastuzumab for HER2 Overexpressing Metastatic Breast Cancer
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Breast Cancer
Keywords: Breast Cancer
Lead sponsor: Hoosier Cancer Research Network
Sponsor class: OTHER
Collaborators: name: Novartis Pharmaceuticals
name: Walther Cancer Institute
First posted: 2005-09-22
Enrollment: 7
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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 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).

Primary outcomes:
measure: Phase I Cohorts:
timeFrame: 18 months
measure: The primary objective is to ensure the safety and tolerability of the combination of Trastuzumab and PTK787,
timeFrame: 18 months
measure: Phase II Cohorts:
timeFrame: 18 months
measure: To assess response rate of PTK787 combined with trastuzumab in patients with newly diagnosed HER2 overexpressing
timeFrame: 18 months
Secondary outcomes:
measure: Phase II Cohorts:
timeFrame: 12 months
measure: To assess the safety and tolerability of PTK787 combined with trastuzumab
timeFrame: 12 months
measure: To assess the time to progression and clinical benefit of PTK787 combined with trastuzumab
timeFrame: 12 months
Other outcomes:
Locations:
city: Elkhart
country: United States
facility: Elkhart Clinic
state: Indiana
city: Fort Wayne
country: United States
facility: Fort Wayne Oncology & Hematology, Inc
state: Indiana
city: Goshen
country: United States
facility: Center for Cancer Care at Goshen Health System
state: Indiana
city: Indianapolis
country: United States
facility: Indiana University Cancer Center
state: Indiana
city: Lafayette
country: United States
facility: Arnett Cancer Care
state: Indiana
city: Muncie
country: United States
facility: Medical Consultants, P.C.
state: Indiana
city: South Bend
country: United States
facility: Northern Indiana Cancer Research Consortium
state: Indiana
city: Terre Haute
country: United States
facility: AP&S Clinic
state: Indiana
Study officials:
affiliation: Hoosier Oncology Group, LLC
name: Kathy Miller, M.D.
role: STUDY_CHAIR
References: