Clinical trial NCT00639366: Radiation Therapy to the Head in Preventing Brain Metastases in Women Receiving Trastuzumab and Chemotherapy for Metastatic or Locally Advanced Breast Cancer
Official title: Prospective Randomised Clinical Trial Testing the Role of Prophylactic Cranial Radiotherapy in Patients Treated With Trastuzumab (Herceptin®) for Metastatic Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Breast Cancer
Keywords: recurrent breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer
stage IV breast cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2008-03-20
Enrollment: 390
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: PREVENTION

Brief summary: 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.

Detailed 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.

Eligibility 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

Primary outcomes:
measure: Incidence of symptomatic brain metastases
Secondary outcomes:
measure: Survival
measure: Cerebral toxicity and quality of life
Other outcomes:
Locations:
city: Basildon
country: United Kingdom
facility: Basildon University Hospital
state: England
city: Ipswich
country: United Kingdom
facility: Ipswich Hospital
state: England
city: Leeds
country: United Kingdom
facility: Leeds Cancer Centre at St. James's University Hospital
state: England
city: Liverpool
country: United Kingdom
facility: Royal Liverpool University Hospital
state: England
city: Liverpool
country: United Kingdom
facility: Aintree University Hospital
state: England
city: London
country: United Kingdom
facility: Barts and the London School of Medicine
state: England
city: Manchester
country: United Kingdom
facility: Christie Hospital
state: England
city: Merseyside
country: United Kingdom
facility: Clatterbridge Centre for Oncology
state: England
city: Sheffield
country: United Kingdom
facility: Cancer Research Centre at Weston Park Hospital
state: England
city: Swindon
country: United Kingdom
facility: Great Western Hospital
state: England
city: Westcliff-On-Sea
country: United Kingdom
facility: Southend University Hospital NHS Foundation Trust
state: England
city: York
country: United Kingdom
facility: Cancer Care Centre at York Hospital
state: England
city: Dumfries
country: United Kingdom
facility: Dumfries & Galloway Royal Infirmary
state: Scotland
city: Dundee
country: United Kingdom
facility: Ninewells Hospital
state: Scotland
city: Edinburgh
country: United Kingdom
facility: Edinburgh Cancer Centre at Western General Hospital
state: Scotland
city: Falkirk
country: United Kingdom
facility: Falkirk and District Royal Infirmary
state: Scotland
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre
state: Scotland
city: Kilmarnock
country: United Kingdom
facility: Crosshouse Hospital
state: Scotland
city: Wishaw
country: United Kingdom
facility: Wishaw General Hospital
state: Scotland
Study officials:
affiliation: University of Glasgow
name: Peter A. Canney, MD
role: PRINCIPAL_INVESTIGATOR
References: