Radiation Therapy to the Head in Preventing Brain Metastases in Women Receiving Trastuzumab and Chemotherapy for Metastatic or Locally Advanced Breast Cancer

Anglo Celtic Cooperative Oncology Group

Status and phase: Completed; Phase 3

Conditions: Breast Cancer

Treatments: Radiation: radiation therapy; Biological: trastuzumab; Drug: chemotherapy

Study type: Interventional

Funder types: Other

Identifiers

NCT00639366

ACCOG-HER-PCI

ISRCTN64624715

CDR0000588868 (Registry Identifier)

EU-20822

Details and patient eligibility

About

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. It is not yet known whether radiation therapy directed at the head is effective in preventing brain metastases in patients with advanced cancer.

PURPOSE: This randomized phase III trial is studying radiation therapy to the head to see how well it works in preventing brain metastases in women receiving trastuzumab and chemotherapy for metastatic or locally advanced breast cancer.

Full description

OBJECTIVES:

• To test if prophylactic cranial radiotherapy delivering 30 Gy in 10 fractions will significantly reduce (from 35% to 21% at 2 years) the incidence of symptomatic brain metastases in patients treated with trastuzumab (Herceptin®) for metastatic breast cancer.

OUTLINE: This is a multicenter study. Patients are stratified by center, type of systemic therapy (trastuzumab [Herceptin®] monotherapy vs combination with chemotherapy), hormone receptor status, and presence of lung metastases (yes vs no). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive taxane/trastuzumab therapy for 6 weeks. While continuing taxane/trastuzumab therapy, patients then undergo 10 fractions of concurrent prophylactic cranial radiotherapy in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients receive taxane/trastuzumab therapy without concurrent prophylactic cranial radiotherapy.

All patients undergo quality of life assessments every 8 weeks for 9 months.

After completion of study treatment, patients are followed periodically for at least 1 year.

Enrollment: 390 estimated patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically proven breast carcinoma

  • Metastatic or locally advanced disease

• Must demonstrate HER2 3+ positivity on IHC or 2+ over-expression and FISH test demonstrating C-erB2 gene amplification

• No known or suspected brain metastases or CNS disease, as defined by the presence of any of the following key symptoms:

  • Headache
  • Nausea and/or vomiting
  • Clinical signs of raised intracranial pressure
  • Seizures
  • Focal symptoms
  • Cognitive dysfunction
  • Affective disorder

• Hormone receptor status not specified

PATIENT CHARACTERISTICS:

• Female
• Postmenopausal status not specified
• ECOG performance status 0 or 1
• Patients must a-priori be suitable for trastuzumab (Herceptin®) +/- chemotherapy in terms of bone marrow, hepatic, and renal function
• No prior history of cerebrovascular disease or neurological disorder including seizures

PRIOR CONCURRENT THERAPY:

• No prior cranial radiotherapy
• No prior neurosurgery