Whole Brain Radiation Therapy With Oxygen, With or Without RSR13, in Women With Brain Metastases From Breast Cancer

Breast Cancer Clinical Trial

— ENRICH  

Official title:

A Phase 3 Randomized, Open-label Comparative Study of Standard Whole Brain Radiation Therapy With Supplemental Oxygen, With or Without Concurrent RSR13 (Efaproxiral), in Women With Brain Metastases From Breast Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00083304
• Other study ID #: RT-016
• Status: Completed
• Phase: Phase 3
• First received: May 18, 2004
• Last updated: May 8, 2013
• Start date: February 2004
• Est. completion date: June 2007

Study information

• Verified date: May 2013
• Source: Spectrum Pharmaceuticals, Inc
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Canada: Health CanadaBrazil: National Health Surveillance AgencySpain: Agencia Española de Medicamentos y Productos SanitariosArgentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia MedicaCroatia: Agency for Medicinal Product and Medical DevicesUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyPeru: Instituto Nacional de SaludItaly: The Italian Medicines AgencyAustria: Agency for Health and Food SafetyLithuania: State Medicine Control Agency - Ministry of HealthGreece: National Organization of MedicinesHungary: National Institute of PharmacyChile: Instituto de Salud Pública de Chile
• Study type: Interventional

Clinical Trial Summary

RSR13 (efaproxiral) is a radiation sensitizer that has shown positive results in a Phase 3, randomized clinical trial of patients with brain metastases. Of 111 eligible breast cancer patients with brain metastases in that trial, 59 patients who received RSR13 prior to radiation therapy had a median survival time that was twice as long as the 52 patients who did not receive RSR13 prior to radiation therapy.

RSR13 (efaproxiral) is an experimental drug that increases the amount of oxygen released from blood into the tissues. It is well known that certain types of cancer tumors, including those in brain metastases, lack oxygen. Lack of oxygen in a tumor can reduce the effect of radiation therapy (RT). RSR13 may increase the oxygen level in brain tumors so that radiation therapy works better.

This study will enroll up to 360 women with brain metastases from breast cancer, and will evaluate if whole brain radiation therapy given with RSR13 will have a better treatment effect than whole brain radiation therapy alone. RSR13 will be infused intravenously (IV) through a central catheter placed in a central vein. Women randomized (assigned) to receive RSR13, therefore, will need to have a central catheter placed for treatment unless one is already in place.

Description:

The screening process will include documentation of the cancer, which which will require a brain scan and may include a liver scan. Other screening measurements will include a Karnofsky Performance Status (KPS) assessment, measurement of the amount of oxygen in the blood, using a non-invasive device most often placed on the finger, lung function tests that will require blowing into a machine, and an electrocardiogram (ECG). About 2 teaspoons, or 10 mL, of blood will be taken for specific laboratory tests, and a pregnancy test will be done on the blood of women of childbearing potential.

All study patients will receive supplemental oxygen and whole brain radiation therapy (WBRT) (30 Gy, 3 Gy fractions) every weekday for 2 weeks. Half of the patients will be randomized (assigned) to receive RSR13 prior to WBRT, and will need to have a central catheter placed for treatment unless one is already in place. Patients who receive RSR13 will also need to continue to receive oxygen in the clinic until the amount of oxygen in their blood is near normal. This level has returned to near normal in most patients within 1 to 2 hours.

During treatment and follow-up visits, physical and neurological exam, KPS assessment, weight, height, and vital sign measurements, and about 2 teaspoons of blood may be required. Patients will need to return for follow-up visits 1 month after completion of treatment, 2 months later, and every 3 months thereafter until their doctor tells them otherwise.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 368
• Est. completion date: June 2007
• Est. primary completion date: June 2007
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adult women with brain metastases from breast cancer

• Minimum KPS of 70

Exclusion Criteria:

• Previous treatment for brain metastases, including brain surgery and any form of radiation to the brain

Study Design

Allocation: Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Metastases
• Neoplasm Metastasis

Intervention

Drug:
• Efaproxiral
75 mg/kg, administered over 30 minutes via a central venous access device (CVAD). Administered 30 minutes prior to the start of whole brain radiation therapy (WBRT) on each WBRT treatment day for 10 days.

Radiation:
• Whole Brain Radiation Therapy (WBRT)
3.0 Gy per day for 10 days (30.0 Gy total) of WBRT.

Other:
• Supplemental Oxygen
4 L/minute by nasal cannula. Administered at least 35 minutes prior to WBRT, during WBRT and until 15 minutes after completion of WBRT on all WBRT treatment days.

Locations

Country	Name	City	State
Argentina	Hospital Espanol	Buenos Aires
Argentina	Instituto de Oncologia A. Roffo	Buenos Aires
Argentina	Instituto Medico Especializado Alexander Fleming	Buenos Aires	Cuidad de Buenos Aires
Argentina	Instituto Privado de Radioterapia y Oncologia	Cordoba
Argentina	Centro de Terapia Radiante Cumbres (CAICI)	Rosario
Austria	LKH-Universitatsklinikum Graz	Graz
Austria	Medical University Innsbruck	Innsbruck
Brazil	Fundação Pio XII - Hospital do Câncer de Barretos	Barretos	SP
Brazil	Hospital Erasto Gaertner	Curitiba
Brazil	Hospital Santa Rita da Irmandade da Santa Casa	Porto Alegre
Brazil	Velindre Hospital	Porto Alegre
Brazil	Instituto Brasileiro de Controle do Cancer	Sao Paulo
Brazil	Hospital Sao Lucas PUC	Teofilo	Fortaleza Ceara
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	Cross Cancer Center	Edmonton	Alberta
Canada	Juravinski Cancer Centre	Hamilton	Ontario
Canada	CHUM - Campus Notre Dame	Montreal	Quebec
Canada	Hopital Maisonneuve-Rosemont	Montreal	Quebec
Canada	McGill University	Montreal	Quebec
Canada	Ottawa Regional Cancer Centre	Ottawa	Ontario
Canada	Hotel-Dieu de Quebec du CHUQ	Quebec City	Quebec
Canada	Centre Hospitalier Universitarie de Service de Radio-Oncologie	Sherbrooke	Quebec
Canada	Princess Margaret Hospital	Toronto	Ontario
Chile	Cilnica Santa Maria	Providencia	Santiago de Chile
Croatia	Clinical Hospital Osijek	Osijek
Croatia	CHU Zagreb University School of Medicine	Zagreb
Croatia	University Hospital for Tumors	Zagreb
France	Centre Georges François Leclerc	Dijon Cedex
France	Centre Oscar Lambret	Lille Cedex
France	Centre Léon Bérard	Lyon Cedex
France	Hopital de Montbeliard	Montbeliard
France	Centre Antioned Lacasagne	Nice
France	Centre Hospitalier Lyon Sud	Pierre-Benite
France	CHU Poitiers	Poitiers
France	Centre Rene Huguenin	Saint-Cloud
France	Clinique Armoricaine de	St. Brieuc
France	Institut Gustave Roussy	Villejuif Cedex
Greece	Hygeia Diagnostic and Therapeutic Center of Athens	Athens
Hungary	University of Debrecen	Debrecen	Hajdú-Bihar
Hungary	University of Szeged	Szeged
Italy	Azienda Ospedaliera Maggiore della Carita	Novara
Italy	Ospedale S Chiara, University of Pisa	Pisa
Lithuania	Kaunas Medical University Hospital	Kaunas
Lithuania	Institute of Oncology, Vilnius University	Vilnius
Peru	Hospital Edgardo Rebagliati Martins (ESSALUD)	Lima
Peru	Instituto de Enfermedades Neoplasicas (INEN)	Lima
Peru	Radiooncologia, Radiation Oncology Center	Lima
Spain	Ciutat Sanitari de Vall d'Hebron	Barcelona
Spain	Instituto Catalan de Oncologia (ICO)	Barcelona
Spain	Hospital Ramon Y Cajal	Madrid
Spain	Clinica Universitaria de Navarra	Pamplona
Spain	Instituto Valenciano de Oncologia	Valencia
United Kingdom	Royal Sussex County Hospital	Brighton
United Kingdom	Beatson Oncolgy Center	Glasgow
United Kingdom	Velindre Hospital	Whitchurch	Cardiff
United States	Dent Neurologic Institute	Amherst	New York
United States	Emory University Winship Cancer Institute	Atlanta	Georgia
United States	Franklin Square Hospital Center	Baltimore	Maryland
United States	Johns Hopkins Oncology Center	Baltimore	Maryland
United States	Maryland Hematology Oncology	Baltimore	Maryland
United States	Alta Bates Comprehensive Cancer Center	Berkeley	California
United States	Center for Cancer and Blood Disorders	Bethesda	Maryland
United States	Boca Raton Community Hospital	Boca Raton	Florida
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Eastchester Center for Cancer Care	Bronx	New York
United States	SUNY Downstate Medical Center	Brooklyn	New York
United States	University of North Carolina Breast Center	Chapel Hill	North Carolina
United States	Northwestern University	Chicago	Illinois
United States	University of Cincinnati Division of Hematology-Oncology	Cincinnati	Ohio
United States	Cleveland Clinic Hospital	Cleveland	Ohio
United States	Ohio State University	Columbus	Ohio
United States	Texas Oncology	Dallas	Texas
United States	Henry Ford Hospital	Detroit	Michigan
United States	Duke University Medical Center	Durham	North Carolina
United States	Texas Oncology	Fort Worth	Texas
United States	Parkview Research Center	Ft. Wayne	Indiana
United States	Indiana University School of Medicine	Indianapolis	Indiana
United States	The University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	University of California at Los Angeles	Los Angeles	California
United States	University of Wisconsin	Madison	Wisconsin
United States	University of Miami Medical	Miami	Florida
United States	University of Minnesota Cancer Center	Minneapolis	Minnesota
United States	Yale University School of Medicine	New Haven	Connecticut
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Virginia G. Piper Cancer Center, Arizona Oncology Services	Phoenix	Arizona
United States	Radiological Associates of Sacramento	Sacramento	California
United States	UCSF - Comprehensive Cancer Center	San Francisco	California
United States	Virginia Mason Cancer Center	Seattle	Washington
United States	Siouxland Regional Cancer Center	Sioux City	Iowa
United States	Washington University School of Medicine	St. Louis	Missouri
United States	University of South Florida - H. Lee Moffitt Cancer Center	Tampa	Florida
United States	Arizona Cancer Center, University of Arizona	Tucson	Arizona
United States	Wenatchee Valley Clinic	Wenatchee	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Spectrum Pharmaceuticals, Inc

Countries where clinical trial is conducted

United States,  Argentina,  Austria,  Brazil,  Canada,  Chile,  Croatia,  France,  Greece,  Hungary,  Italy,  Lithuania,  Peru,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival		Measured from randomization until death due to any cause.	No
Secondary	Response Rate in the Brain at 3 Months		Assessed at screening, 3 months after end of study treatment and at least 4 weeks after the 3-month scan.	No
Secondary	Karnofsky Performance Status & Neurological Signs & Symptoms		Assessed at baseline, 1 month follow-up (FU) visit, 3 month FU visit, and 6 month FU visit.	No