PTK787 + Trastuzumab for HER2 Overexpressing Metastatic Breast Cancer

Hoosier Cancer Research Network

Status and phase

Terminated

Phase 2

Phase 1

Conditions

Breast Cancer

Treatments

Drug: PTK787

Drug: Trastuzumab

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT00216047

HOG BRE04-80

Details and patient eligibility

About

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.

Full 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

Enrollment

7 patients

Sex

Female

Ages

18+ years old

Volunteers

No Healthy Volunteers

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).