Clinical trial NCT00003563: Radiation Therapy Plus Gadolinium Texaphyrin in Treating Patients With Brain Metastases
Official title: Phase III Randomized Trial of Gadolinium Texaphyrin (PCI-0120) Injection as a Radiation Sensitizer in Patients Receiving Whole Brain Radiation Therapy for the Treatment of Brain Metastases
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Metastatic Cancer
Keywords: tumors metastatic to brain
Lead sponsor: Pharmacyclics LLC.
Sponsor class: INDUSTRY
First posted: 2004-04-30
Enrollment: 430
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Gadolinium texaphyrin may increase the effectiveness of radiation therapy by making tumor cells more sensitive to radiation. It is not yet known whether giving gadolinium texaphyrin with radiation therapy is more effective than radiation therapy alone in treating brain metastases.

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

Detailed description: OBJECTIVES: I. Determine the safety of gadolinium texaphyrin administered prior to whole brain radiotherapy in patients with brain metastases. II. Compare the efficacy and toxicity of whole brain radiotherapy with or without gadolinium texaphyrin in these patients. III. Assess the quality of life of these patients.

OUTLINE: This is a randomized, two stage, multicenter study. Patients are stratified according to RTOG recursive partitioning analysis class (RPA class 1 vs class 2) and tumor type (breast vs lung vs other). Stage 1 (lead-in): All patients receive gadolinium texaphyrin IV over 5-10 minutes on the 10 days that they receive radiotherapy. Approximately 2-5 hours later, patients undergo whole brain radiotherapy. Stage 2 (randomization): Patients are randomized to one of two treatment arms. Patients in arm I undergo whole brain radiotherapy for 10 days. Patients in arm II receive gadolinium texaphyrin and radiotherapy as in stage 1. Quality of life is assessed on days 10 and 28, then monthly for 5 months, and then every 3 months thereafter. Patients are followed at day 28, then monthly for 5 months, and then every 3 months until death.

PROJECTED ACCRUAL: The lead-in phase will accrue at least 25-30 patients and the randomization phase will accrue 400 patients (200/arm) over a 12 month period.

Eligibility criteria: DISEASE CHARACTERISTICS: Histologically proven solid tumor with parenchymal brain metastasis Solitary metastasis eligible only if refused surgery or surgical resection deemed inappropriate No leptomeningeal metastases or subarachnoid spread of tumor No small cell lung cancer, germ cell tumors, lymphoma, or leukemia No liver metastases, unless from breast cancer No more than 1 site of extracranial metastases (multiple bone or lung metastases count as one site), unless from breast cancer Hormone receptor status: Not specified

PATIENT CHARACTERISTICS: Age: 18 and over Menopausal status: Not specified Performance status: Karnofsky 70-100% Life expectancy: Not specified Hematopoietic: Absolute neutrophil count at least 1,500/mm3 Platelet count at least 50,000/mm3 Hepatic: Bilirubin no greater than 2 times upper limit of normal (ULN) AST and ALT no greater than 2 times ULN Renal: Creatinine no greater than 2.0 mg/mL Other: No history of porphyria No history of G6PD deficiency HIV negative No other major medical illnesses No major psychiatric impairment Not pregnant or nursing Negative pregnancy test

PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No chemotherapy during and for 2 weeks after gadolinium texaphyrin therapy Endocrine therapy: Concurrent hormonal therapy allowed Radiotherapy: No prior cranial radiation, including prior stereotactic radiosurgery No plan for radiosurgery or radiation boost following whole brain radiotherapy Concurrent radiotherapy allowed to other sites, except kidneys and liver Surgery: No prior subtotal or total resection of brain metastases (except biopsies)

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Greenbrae
country: United States
facility: Marin Oncology Associates, Inc.
state: California
city: Los Angeles
country: United States
facility: Kaiser Permanente Medical Group
state: California
city: Los Angeles
country: United States
facility: Jonsson Comprehensive Cancer Center, UCLA
state: California
city: Los Angeles
country: United States
facility: Beckman Research Institute, City of Hope
state: California
city: Sacramento
country: United States
facility: Radiation Oncology Center - Sacramento
state: California
city: Denver
country: United States
facility: University of Colorado Cancer Center
state: Colorado
city: Port Charlotte
country: United States
facility: Charlotte County Radiation Therapy Regional Center
state: Florida
city: Atlanta
country: United States
facility: Emory Clinic
state: Georgia
city: Indianapolis
country: United States
facility: Indiana University Cancer Center
state: Indiana
city: Metairie
country: United States
facility: Hematology and Oncology Services - Metairie
state: Louisiana
city: Boston
country: United States
facility: Massachusetts General Hospital Cancer Center
state: Massachusetts
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Detroit
country: United States
facility: Harper Hospital and Wayne State University
state: Michigan
city: Minneapolis
country: United States
facility: Veterans Affairs Medical Center - Minneapolis
state: Minnesota
city: Minneapolis
country: United States
facility: North Memorial Research Center
state: Minnesota
city: New Brunswick
country: United States
facility: Cancer Institute of New Jersey
state: New Jersey
city: Albuquerque
country: United States
facility: New Mexico Oncology-Hematology
state: New Mexico
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Cincinnati
country: United States
facility: Barrett Cancer Center, The University Hospital
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Center
state: Ohio
city: Meadowbrook
country: United States
facility: Abington Hematology Oncology Associates
state: Pennsylvania
city: Philadelphia
country: United States
facility: Kimmel Cancer Center of Thomas Jefferson University - Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Presbyterian-University Hospital
state: Pennsylvania
city: Scranton
country: United States
facility: Mercy Hospital Cancer Center - Scranton
state: Pennsylvania
city: Knoxville
country: United States
facility: Thompson Cancer Survival Center
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt Cancer Center
state: Tennessee
city: Houston
country: United States
facility: University of Texas - MD Anderson Cancer Center
state: Texas
city: Temple
country: United States
facility: Scott and White Memorial Hospital
state: Texas
city: Seattle
country: United States
facility: Virginia Mason Medical Center
state: Washington
city: Madison
country: United States
facility: University of Wisconsin Comprehensive Cancer Center
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Hamilton
country: Canada
facility: Cancer Care Ontario-Hamilton Regional Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Montreal
country: Canada
facility: Montreal General Hospital
state: Quebec
Study officials:
affiliation: Pharmacyclics LLC.
name: Markus Renschler, MD
role: STUDY_CHAIR
References:
citation: Li J, Bentzen SM, Li J, Renschler M, Mehta MP. Relationship between neurocognitive function and quality of life after whole-brain radiotherapy in patients with brain metastasis. Int J Radiat Oncol Biol Phys. 2008 May 1;71(1):64-70. doi: 10.1016/j.ijrobp.2007.09.059.
citation: Li J, Bentzen SM, Renschler M, Mehta MP. Regression after whole-brain radiation therapy for brain metastases correlates with survival and improved neurocognitive function. J Clin Oncol. 2007 Apr 1;25(10):1260-6. doi: 10.1200/JCO.2006.09.2536.