Surgery and Whole Brain Radiotherapy (RT) Versus Whole Brain Radiotherapy (RT) and Radiosurgery for 1-3 Resectable Brain Metastases

Surgery and Whole Brain Radiotherapy Versus Whole Brain Radiotherapy and Radiosurgery for 1-3 Resectable Brain Metastases: Phase III Prospective Pilot Study

Patients in good general condition with resectable brain metastases, looks better with more intense treatment of metastases. This local treatment has been accomplished with surgery or radiosurgery. However, there are no randomized studies comparing these two types of treatment. The purpose of this study is to make this.

Study Overview

• Status: Withdrawn
• Conditions: Cancer; Metastases
• Intervention / Treatment: Other: surgery; Radiation: radiosurgery

Detailed Description

Patients in good general condition with resectable 1-3 brain metastases will be randomized to surgery and whole brain radiotherapy and whole brain radiotherapy and radiosurgery. Initially we will evaluate the feasibility of carrying out the study with 15 patients in each arm, and after, we will follow with the primary end-point of comparing the toxicity of the exclusively radiotherapy arm with complications of the surgical arm. As a secondary end-point, we will evaluate local recurrence-free survival, overall survival, distance cerebral relapse-free survival (metachronous brain metastasis), free of neurological progression survival, free of neurological death survival, free of dependent life (another person)survival , steroid-free survival and quality of life.

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • São Paulo
    • Barretos, São Paulo, Brazil, 14784400
      • Barretos Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histopathology of primary tumors: all but primary small cell cancer, germ cell tumors, leukemia, lymphoma, or primary central nervous system.
• Primary-site: controlled, meaning operated and / or irradiated; without detectable local tumor activity
• Lack of extra-cranial metastases
• Absence of prior brain irradiation
• Number of brain metastases: 1-3
• Location of brain metastases: brain regions eligible for surgery (non-eloquent areas) and RC (metastases with largest diameter ≤ 3 cm, volume <15 mL, and> 5 mm from the optic chiasm, optic nerves, thalamus, hypothalamus, basal ganglia base, optic tract, optic radiation, midbrain, pons, medulla, corpus callosum, internal capsule, hippocampus and amygdala, and <10 ml of brain tissue receiving ≥ 12 Gy).
• Metastasis-that does not cause significant mass effect and hydrocephalus or herniation requiring urgent surgical intervention
• Second uncontrolled primary tumor site: none, except non-melanoma skin cancer
• Absence of comorbid conditions that prevents surgery for resection of brain metastases
• Absence of connective tissue disease such as lupus erythematosus or scleroderma
• Patients in chemotherapy need to have their chemotherapy treatment suspended.
• Patients must consent to be followed by clinical staff of the Barretos Cancer Hospital (HCB).
• KPS: ≥ 70%
• Neutrophils ≥ 1800 cells / mL until 14 days prior to study entry
• Platelets ≥ 100,000 cells / mL until 14 days prior to study entry
• Hemoglobin ≥ 10 g / dL 14 days prior to entering the study (transfusion is allowed to achieve required concentration)
• Creatinine ≤ 1.7 mg / dL 14 days prior to study entry
• BUN ≤ 30 mg / dL 14 days prior to entry on study
• Bilirubin ≤ 2 mg / dL 14 days prior to study entry
• TGO/TGP Up to three times normal on examination until 14 days prior to study entry Prothrombin time-INR <1.4 at examination until 14 days prior to study entry
• Systolic pressure ≤ 160 mm Hg and diastolic pressure ≤ 90 mm Hg at examination until 14 days prior to study entry Electrocardiogram-without acute myocardial infarction in examination until 14 days prior to study entry
• No active bleeding or pathological condition that entails high risk of bleeding
• Negative pregnancy test at least 14 days prior to study entry
• Informed Consent: The patient will be informed of the investigational nature of treatment and only enter the study after agreeing to participate in the study signed a consent form that informs the side effects and possible benefits and potential of both modalities treatment.

Exclusion Criteria:

• Metastasis in the posterior fossa, because this patient will be operated.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: surgery+whole-brain irradiation; brain metastases is resected and the patient is submitted to whole-brain irradiation	Other: surgery; resection of brain metastases; Other Names: neurosurgery
Active Comparator: whole-brain irradiation+radiosurgery; patients will be submitted to whole-brain irradiation and after, they will be submitted to radiosurgery.	Radiation: radiosurgery; radiosurgery to brain metastases; Other Names: stereotactic radiosurgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
feasibility	One year after the start of patient recruitment, the study will be analyzed for feasibility and, if feasible, we will pursue the study with primary end-point of comparing the toxicity of exclusive radiation therapy arm with the surgical arm.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
complications and toxicity	One year after the start of patient recruitment, the study will be analyzed for toxicity of the radiotherapy arm versus the arm surgical complications, and if compatible, will continue the study until 70 patients in each arm.	1 year

Collaborators and Investigators

• Sponsor: Barretos Cancer Hospital
• Investigators: Principal Investigator: Ricardo A Nakamura, MD, Barretos Cancer Hospital

Study record dates

Study Major Dates

• Study Start: July 1, 2010
• Primary Completion (Actual): July 1, 2010
• Study Completion (Actual): July 1, 2010

Study Registration Dates

• First Submitted: July 22, 2010
• First Submitted That Met QC Criteria: July 23, 2010
• First Posted (Estimate): July 26, 2010

Study Record Updates

• Last Update Posted (Estimate): February 4, 2014
• Last Update Submitted That Met QC Criteria: February 2, 2014
• Last Verified: February 1, 2014

More Information

Terms related to this study

• Keywords: radiotherapy; surgery; radiosurgery; brain metastases; neurosurgery; resectable brain metastases
• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms; Neoplasms by Site; Neoplastic Processes; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasm Metastasis; Brain Neoplasms; Neoplasms, Second Primary
• Other Study ID Numbers: 3602010