Clinical trial NCT00005887: Radiation Therapy With or Without RSR13 in Treating Patients With Brain Metastases
Official title: A Phase III, Randomized, Open-Label, Comparative Study of Standard Whole Brain Radiation Therapy With or Without RSR13 in Patients With Brain Metastases
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Metastatic Cancer
Keywords: tumors metastatic to brain
Lead sponsor: Spectrum Pharmaceuticals, Inc
Sponsor class: INDUSTRY
First posted: 2003-08-29
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs such as RSR13 may make tumor cells more sensitive to radiation therapy.

PURPOSE: Randomized phase III trial to compare the effectiveness of radiation therapy to the brain with or without RSR13 in treating patients who have brain metastases.

Detailed description: OBJECTIVES:

* Compare the median survival time in patients with brain metastases after receiving treatment with whole brain radiotherapy with or without RSR13.
* Compare the response rate to these treatment regimens in these patients.
* Compare the time to progression after receiving these treatment regimens in these patients.
* Compare quality of life in these patients receiving these treatment regimens.
* Compare cause of death (neurologic vs nonneurologic death) in these patients after receiving these treatment regimens.
* Determine the safety of RSR13 in these patients.
* Assess the pharmacokinetics of RSR13 in these patients.

OUTLINE: This is a randomized, open label, comparative, multicenter study. Patients are stratified according to the Radiation Therapy Oncology Group RPA Class (I vs II). Patients are further stratified within the RPA class II stratum according to site of primary cancer (non-small cell lung cancer vs breast vs other). Patients are randomized to one of two treatment arms.

* Arm I: Patients receive whole brain radiotherapy 5 days a week for two weeks in conjunction with supplemental oxygen breathing.
* Arm II: Patients receive RSR13 IV over 30 minutes followed by whole brain radiotherapy and supplemental oxygen breathing as in arm I.

Quality of life is assessed at the first and last day of radiotherapy, at 1 month, 3 months, and then every 3 months until disease progression.

Patients are followed at 1 month, 3 months, every 3 months until disease progression, and then for survival.

PROJECTED ACCRUAL: A maximum of 408 (204 per treatment arm) patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Radiographically, histologically, or cytologically confirmed brain metastases with histologically or cytologically confirmed primary malignancy except the following:

  * Small cell lung cancer, germ cell tumors, and lymphomas
* No leptomeningeal metastases

PATIENT CHARACTERISTICS:

Age:

* 18 and over

Performance status:

* Karnofsky 70-100%

Life expectancy:

* Not specified

Hematopoietic:

* Hemoglobin at least 10 g/dL
* WBC at least 2,000/mm3
* Platelet count at least 75,000/mm3

Hepatic:

* Bilirubin no greater than 2.0 mg/dL
* ALT and AST no greater than 3 times upper limit of normal

Renal:

* Creatinine no greater than 2.0 mg/dL

Pulmonary:

* Forced vital capacity and forced expiratory volume at least 50% of normal in patients with significant intrathoracic tumor involvement, chronic obstructive pulmonary disease, interstitial lung disease, or pulmonary embolism
* Resting and exercise oxygen saturation at least 90% on room air

Other:

* No other concurrent active malignancy from a second histologic site
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* No prior biologic therapy or immunotherapy for brain metastases
* At least 28 days since prior investigational biologic therapy

Chemotherapy:

* No prior chemotherapy for brain metastases
* No chemotherapy for brain metastases for at least one month following radiation therapy
* At least 7 days since prior chemotherapy for primary tumor or extracranial metastases
* No planned chemotherapy during radiation therapy

Endocrine therapy:

* No prior hormonal therapy for brain metastases
* Prior or concurrent corticosteroid therapy allowed

Radiotherapy:

* No prior whole brain radiotherapy for brain metastases
* No prior stereotactic radiosurgery for brain metastases

Surgery:

* Prior surgery allowed for brain metastases if at least one measurable lesion remains

Other:

* At least 28 days since prior investigational drug or device
* No prior RSR13

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: St. Joseph's Hospital and Medical Center
state: Arizona
city: Tucson
country: United States
facility: Arizona Cancer Center
state: Arizona
city: Berkeley
country: United States
facility: Alta Bates Comprehensive Cancer Center
state: California
city: Greenbrae
country: United States
facility: California Cancer Care, Inc.
state: California
city: La Jolla
country: United States
facility: Scripps Green Hospital & Scripps Clinic
state: California
city: Los Angeles
country: United States
facility: Tower Hematology Oncology Medical Group
state: California
city: Denver
country: United States
facility: University of Colorado Cancer Center
state: Colorado
city: Boca Raton
country: United States
facility: Comprehensive Cancer Care Specialists of Boca Raton
state: Florida
city: Inverness
country: United States
facility: Citrus Memorial Hospital
state: Florida
city: Decatur
country: United States
facility: Decatur Memorial Hospital Cancer Care Institute
state: Illinois
city: New Orleans
country: United States
facility: Ochsner Clinic
state: Louisiana
city: Baltimore
country: United States
facility: Harbor Hospital Center
state: Maryland
city: Baltimore
country: United States
facility: St. Agnes Healthcare
state: Maryland
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: Burlington
country: United States
facility: Lahey Clinic - Burlington
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusetts Memorial Medical Center
state: Massachusetts
city: Camden
country: United States
facility: Cooper Hospital/University Medical Center
state: New Jersey
city: Long Branch
country: United States
facility: Monmouth Medical Center
state: New Jersey
city: Toms River
country: United States
facility: East Coast Radiation Oncology
state: New Jersey
city: Buffalo
country: United States
facility: Millard Fillmore Hospital
state: New York
city: Syracuse
country: United States
facility: State University of New York - Upstate Medical University
state: New York
city: Winston-Salem
country: United States
facility: Comprehensive Cancer Center at Wake Forest University
state: North Carolina
city: Bismarck
country: United States
facility: Bismarck Cancer Center
state: North Dakota
city: Akron
country: United States
facility: Akron General Medical Center
state: Ohio
city: Akron
country: United States
facility: Akron City Hospital
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Center
state: Ohio
city: Philadelphia
country: United States
facility: Kimmel Cancer Center of Thomas Jefferson University - Philadelphia
state: Pennsylvania
city: Memphis
country: United States
facility: Memphis Regional Brain Tumor Center
state: Tennessee
city: Memphis
country: United States
facility: Boston Baskin Cancer Group, University Tennessee Oncology/Hematology Group
state: Tennessee
city: Dallas
country: United States
facility: U.S. Oncology Research Inc.
state: Texas
city: Houston
country: United States
facility: University of Texas - MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: Danville
country: United States
facility: Center for Radiation Oncology
state: Virginia
city: Richmond
country: United States
facility: Massey Cancer Center
state: Virginia
city: Milwaukee
country: United States
facility: Veterans Affairs Medical Center - Milwaukee (Zablocki)
state: Wisconsin
city: Sydney
country: Australia
facility: Royal Prince Alfred Hospital Medical Center
state: New South Wales
city: Herston
country: Australia
facility: Queensland Radium Institute
state: Queensland
city: East Melbourne
country: Australia
facility: Peter MacCallum Cancer Institute
state: Victoria
city: Heidelberg West
country: Australia
facility: Austin and Repatriation Medical Centre
state: Victoria
city: Brussels (Bruxelles)
country: Belgium
facility: Institut Jules Bordet
city: Brussels (Bruxelles)
country: Belgium
facility: Academisch Ziekenhuis der Vrije Universiteit Brussel
city: Gent
country: Belgium
facility: UZ De Pintelaan
city: Leuven
country: Belgium
facility: U.Z. Gasthuisberg
city: Calgary
country: Canada
facility: Tom Baker Cancer Center - Calgary
state: Alberta
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Surrey
country: Canada
facility: British Columbia Cancer Agency - Fraser Valley Cancer Centre
state: British Columbia
city: Vancouver
country: Canada
facility: British Columbia Cancer Agency
state: British Columbia
city: Winnipeg
country: Canada
facility: St. Boniface General Hospital
state: Manitoba
city: St. Johns
country: Canada
facility: Newfoundland Cancer Treatment and Research Foundation
state: Newfoundland and Labrador
city: Halifax
country: Canada
facility: Nova Scotia Cancer Centre
state: Nova Scotia
city: Ottawa
country: Canada
facility: Ottawa Regional Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Fleurimont
country: Canada
facility: CHUS-Hopital Fleurimont
state: Quebec
city: Montreal
country: Canada
facility: Maisonneuve-Rosemont Hospital
state: Quebec
city: Montreal
country: Canada
facility: Centre Hospitalier de l'Universite de Montreal
state: Quebec
city: Montreal
country: Canada
facility: McGill University
state: Quebec
city: Quebec City
country: Canada
facility: Centre Hospitalier Universitaire de Quebec
state: Quebec
city: Regina
country: Canada
facility: Allan Blair Cancer Centre
state: Saskatchewan
city: Dijon
country: France
facility: Centre de Lutte Contre le Cancer, Georges-Francois Leclerc
city: Marseille
country: France
facility: CHU de la Timone
city: Montbeliard
country: France
facility: Hopital de Montbeliard
city: Pierre Benite
country: France
facility: Centre Hospitalier Lyon Sud
city: Freiburg
country: Germany
facility: Radiologische Uniklink
city: Hamburg
country: Germany
facility: Universitats-Krankenhaus Eppendorf
city: Budapest
country: Hungary
facility: Uzsoki Hospital
city: Debrecen
country: Hungary
facility: University of Debrecen
city: Gydr
country: Hungary
facility: Petz Aladar County Hospital
city: Miskolc
country: Hungary
facility: Borsod-Abauj-Zemplen County Hospital
city: Szeged
country: Hungary
facility: Szeged University
city: Aviano
country: Italy
facility: Centro di Riferimento Oncologico - Aviano
city: Milano
country: Italy
facility: Istituto Europeo Di Oncologia
city: Newcastle Upon Tyne
country: United Kingdom
facility: Newcastle General Hospital
state: England
city: Edinburgh
country: United Kingdom
facility: Western General Hospital
state: Scotland
Study officials:
affiliation: Wake Forest University Health Sciences
name: Edward G. Shaw, MD
role: STUDY_CHAIR
References:
citation: Suh JH, Stea B, Nabid A, Kresl JJ, Fortin A, Mercier JP, Senzer N, Chang EL, Boyd AP, Cagnoni PJ, Shaw E. Phase III study of efaproxiral as an adjunct to whole-brain radiation therapy for brain metastases. J Clin Oncol. 2006 Jan 1;24(1):106-14. doi: 10.1200/JCO.2004.00.1768. Epub 2005 Nov 28.
citation: Nabid A, Kresl J, Stea B, et al.: Standard whole brain radiation (WBRT) with supplemental oxygen (O2) with or without RSR13 (efaproxiral) in patients with brain metastases originating from NSCLC: results of a subgroup analysis. [Abstract] J Clin Oncol 22 (Suppl 14): A-7115, 645s, 2004.
citation: Shaw E, Stea B, Pinter T, et al.: Pharmacokinetics (PK) of RSR13 (efaproxiral) predict survival in patients with brain metastases randomized to receive whole brain radiation therapy (WBRT) with or without RSR13 (REACH RT-009). [Abstract] J Clin Oncol 22 (Suppl 14): A-1561, 122s, 2004.
citation: Stea B, Suh J, Shaw E, et al.: Efaproxiral (EFAPROXYN) as an adjunct to whole brain radiation therapy for the treatment of brain metastases originating from breast cancer: updated survival results of the randomized REACH (RT-009) study. [Abstract] Breast Cancer Res Treat 88 (1): A-4064, 2004.
citation: Suh J, Stea BD, Nabid A, et al.: Prognostic factors for survival in patients with brain metastases enrolled on a worldwide phase 3 randomized trial of 538 patients (study RSR13 RT-009). [Abstract] Int J Radiat Oncol Biol Phys 60 (1 Suppl 1): A-60, S165, 2004.
citation: Suh J, Stea B, Nabid A, et al.: Standard whole brain radiation therapy (WBRT) with supplemental oxygen (O2), with or without RSR13 (efaproxiral) in patients with brain metastases: results of the randomized REACH (RT-009) study. [Abstract] J Clin Oncol 22 (Suppl 14): A-1534, 115s, 2004.