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

Brain Neoplasms Clinical Trial

Official title:

Phase II Randomized Study: Whole Brain Radiotherapy and Concomitant Temozolomide, Compared With Whole Brain Radiotherapy for Brain Metastases Treatment

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01015534
• Other study ID #: 006/004/TEI
• Status: Completed
• Phase: Phase 2
• First received: November 17, 2009
• Last updated: March 25, 2013
• Start date: January 2006
• Est. completion date: October 2009

Study information

• Verified date: March 2013
• Source: Instituto Nacional de Cancerologia de Mexico
• Contact: n/a
• Is FDA regulated: No
• Health authority: Mexico: Federal Commission for Protection Against Health Risks
• Study type: Interventional

Clinical Trial Summary

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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 55
• Est. completion date: October 2009
• Est. primary completion date: October 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain Neoplasms

Intervention

Drug:
• Temozolomide

Radiation:
• Whole brain irradiation

Locations

Country	Name	City	State
Mexico	Instituto Nacional de Cancerología de México	México	D.F

Sponsors (1)

Lead Sponsor	Collaborator
Instituto Nacional de Cancerologia de Mexico

Country where clinical trial is conducted

Mexico, 

References & Publications (3)

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rates. Assessed With Cranial MRI	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.	90 days	No
Secondary	Survival Free of Brain Metastases Progression (PFS of BM)	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.	at 90 days	No
Secondary	Overall Survival	Overall survival:Time in months measured from treatment initiation until the date of death or the date of last follow-up.	1 year	No
Secondary	Number of Grade 3-4 Adverse Events (AE) That Are Definitely or Probably Related to Both Groups of Treatment.	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.	4 months	No