Whole Brain Radiotherapy With or Without Temozolomide at Daily Fixed-dose for Brain Metastases Treatment - Full Text View

Purpose

RATIONALE

Fractionated radiotherapy uses high-energy photons to kill, or damage tumor cells. High daily dose temozolomide combined with fractionated radiotherapy may make tumor cells more sensible to treatment.

PURPOSE

This randomized phase II trial, assess in patients with brain metastases from solid tumors, whether the whole brain radiotherapy (WBRT) plus temozolomide is able to improve the results obtained with WBRT.

Condition	Intervention	Phase
Brain Neoplasms	Drug: Temozolomide Radiation: Whole brain irradiation	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Phase II Randomized Study: Whole Brain Radiotherapy and Concomitant Temozolomide, Compared With Whole Brain Radiotherapy for Brain Metastases Treatment

Resource links provided by NLM:

MedlinePlus related topics: Brain Cancer Cancer

Drug Information available for: Temozolomide

U.S. FDA Resources

Further study details as provided by Instituto Nacional de Cancerologia de Mexico:

Primary Outcome Measures:

Objective Response Rates. Assessed With Cranial MRI [ Time Frame: 90 days ] [ Designated as safety issue: No ]
Objective Response (OR) encompassed the number of participants with Complete Response (CR) and the number of participants with Partial Response (PR). CR is the disappearance of all brain metastases, assessed between two or more cranial MRI. PR is at least a 30% decrease in the sum of the longest diameter of the brain metastases, taking as reference the baseline sum longest diameter, assessed between two or more cranial MRI.

Objective Response Rate (ORR) is the ratio between the number of participants with objective response and the total number of participants.

Secondary Outcome Measures:

Survival Free of Brain Metastases Progression (PFS of BM) [ Time Frame: at 90 days ] [ Designated as safety issue: No ]
Progression free survival of brain metastases is the survival of participants without progressive brain metastases or without neurological symptoms. The progressive brain metastases (PBM) were evaluated with cranial MRI. The PBM were defined as an increase of at least 20% in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new metastases.
Overall Survival [ Time Frame: 1 year ] [ Designated as safety issue: No ]
Overall survival:Time in months measured from treatment initiation until the date of death or the date of last follow-up.
Number of Grade 3-4 Adverse Events (AE) That Are Definitely or Probably Related to Both Groups of Treatment. [ Time Frame: 4 months ] [ Designated as safety issue: No ]
AE, evaluated and graded according to the NCI common terminology criteria (NCI-CTCAE) v3.0

Grade 3 Severe AE.

Grade 4 Life-threatening or disabling AE.

Enrollment:	55
Study Start Date:	January 2006
Study Completion Date:	October 2009
Primary Completion Date:	October 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Whole brain irradiation plus Temozolomide Whole brain irradiation at a dose of 30 Gy in 10 daily fractions over 2 weeks, and a fixed dose of oral Temozolomide, 1h before each fraction of whole brain irradiation, 200 mg on Monday, Wednesday, Friday; 300 mg on Tuesday, and Thursday. Without adjuvant cycles of Temozolomide.	Drug: Temozolomide Other Names: Temodar or Temodal Radiation: Whole brain irradiation Other Name: Whole brain radiotherapy
Active Comparator: Whole brain irradiation Whole brain irradiation at a dose of 30 Gy in 10 daily fractions over 2 weeks	Radiation: Whole brain irradiation Other Name: Whole brain radiotherapy

Detailed Description:

Primary Outcome Measures

Objective Response Rates

Secondary Outcome Measures

Survival Free of Brain Metastases progression
Overall Survival
Systemic Side effects

Objectives

Primary

Compare objective response rates in both arms of treatment

Secondary

Compare survival free of progression in both arms of treatment
Compare Overall Survival in both arms of treatment
Compare side effects

Eligibility

Ages Eligible for Study:	18 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Karnofsky performance status (KPS) ≥ 50
Life expectancy ≥ 12 weeks
Histologically confirmed non lymphomatous solid tumors at primary site
Brain metastases diagnosed with cranial MRI/CT.
Extracranial metastases or primary tumor uncontrolled are allowed
Hemoglobin ≥ 10 g/dl
Absolute neutrophil count of > 1500/mm3
Platelet count of ≥ 100,000/mm3
Blood urea nitrogen (BUN) ≤ 25 mg/dl,
Serum creatinin ≤ 1.5 mg/dl
Serum bilirubins ≤ 1.5 mg/dl,
Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) ≤ twice the upper normal limit

Exclusion Criteria

Pregnant or breast feeding woman
History of allergic reaction to iodinated contrast media
Inability to swallow
Systemic chemotherapy in previous 3 weeks
Oral chemotherapy in previous 2 weeks
Prior surgery, chemotherapy, or radiotherapy for a brain neoplasm
Meningeal carcinomatosis

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01015534

Locations

Mexico
Instituto Nacional de Cancerología de México
México, D.F, Mexico, 14080

Sponsors and Collaborators

Instituto Nacional de Cancerologia de Mexico

Investigators

Principal Investigator:

Carlos Gamboa-Vignolle, MD

Instituto Nacional de Cancerología de México

More Information

Publications:

Jones SF, Greco FA, Gian VG, Miranda FT, Raefsky EL, Hainsworth JD, Willcutt NT, Beschorner AF, Kennerly G, Burris HA 3rd. A Phase I trial of protracted oral fixed-dose temozolomide. Cancer. 2005 Nov 1;104(9):1985-91.

Antonadou D, Paraskevaidis M, Sarris G, Coliarakis N, Economou I, Karageorgis P, Throuvalas N. Phase II randomized trial of temozolomide and concurrent radiotherapy in patients with brain metastases. J Clin Oncol. 2002 Sep 1;20(17):3644-50.

Verger E, Gil M, Yaya R, Viñolas N, Villà S, Pujol T, Quintó L, Graus F. Temozolomide and concomitant whole brain radiotherapy in patients with brain metastases: a phase II randomized trial. Int J Radiat Oncol Biol Phys. 2005 Jan 1;61(1):185-91.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Gamboa-Vignolle C, Ferrari-Carballo T, Arrieta Ó, Mohar A. Whole-brain irradiation with concomitant daily fixed-dose temozolomide for brain metastases treatment: a randomised phase II trial. Radiother Oncol. 2012 Feb;102(2):187-91. Epub 2012 Jan 16.

Responsible Party:	Carlos Gamboa Vignolle, Radiation Oncologist, Instituto Nacional de Cancerologia de Mexico
ClinicalTrials.gov Identifier:	NCT01015534 History of Changes
Other Study ID Numbers:	006/004/TEI
Study First Received:	November 17, 2009
Results First Received:	August 23, 2012
Last Updated:	March 25, 2013
Health Authority:	Mexico: Federal Commission for Protection Against Health Risks

Keywords provided by Instituto Nacional de Cancerologia de Mexico:

Brain metastases
Temozolomide
Whole-brain radiotherapy
Phase II trial

Additional relevant MeSH terms:

Brain Neoplasms
Neoplasms
Neoplasm Metastasis
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neoplastic Processes

Pathologic Processes
Temozolomide
Dacarbazine
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on June 17, 2013