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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Carlos Gamboa Vignolle, Instituto Nacional de Cancerologia de Mexico
ClinicalTrials.gov Identifier:
NCT01015534
First received: November 17, 2009
Last updated: March 25, 2013
Last verified: March 2013
  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:


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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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 August 18, 2014