Whole Brain Radiotherapy Versus Volumetric Modulated Arc Therapy for Brain Metastases

Brain Metastases Clinical Trial

— Amadeus  

Official title:

A Randomized Phase II Study of 20 Gy in 5 Fractions Whole Brain Radiotherapy Versus 15 Gy in 1 Fraction Volumetric Modulated Arc Therapy for One to Ten Brain Metastases

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02220491
• Other study ID #: H14-02032
• Status: Completed
• Phase: N/A
• Start date: October 1, 2014
• Est. completion date: May 18, 2020

Study information

• Verified date: May 2020
• Source: British Columbia Cancer Agency
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Patients with brain metastases with expected life expectancy of 3-6 months are typically treated with radiotherapy to the whole brain giving a dose of 20 Gy over a 5 day period. This study will compare this with volumetric modulated arc therapy (VMAT) which is capable of delivering 15 Gy in one single session to identified disease within the brain but sparing the normal surrounding brain tissue. Primarily the study will assess whether it is possible to recruit sufficient patient numbers to a trial of this type. It will also compare effectiveness, side effects and quality of life between the two treatment methods.

Description:

This is a Phase II prospective clinical trial. Pre treatment evaluations include estimation of life expectancy, Creatinine (GFR) and MRI brain with contrast. An assessment of cognitive function using Montreal Cognitive Assessment questionnaire, assessment of daily living activities using the Modified Barthel's index and quality of life assessment using EORTC QLQ-PAL-15 & BN-20 questionnaires will be performed in clinic. Karnofsky Performance Status will also be assessed by the clinician. If all assessments are within the eligibility criteria then the patient can be recruited. Before treatment begins a history documenting baseline symptoms using NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 and a neurological examination documenting baseline deficits must be obtained.

If patient is randomized to standard treatment of whole brain radiotherapy (WBRT) then subjects will have a non-contrast CT scan using a slice thickness of 2.5 mm or less to plan radiotherapy. If patient are randomized to single fraction radiotherapy then a contrast CT will be used as this aids in identifying metastatic tumours within the brain. Also for the single fraction arm if a contrast-enhanced diagnostic MRI was obtained ≤ 10 days before the CT planning scan, with a single-plane high-resolution sequence or low-resolution sequences in two planes, it can be used for treatment planning. If the contrast-enhanced diagnostic MRI was obtained > 10 days before the CT planning scan or there is no diagnostic MRI, the subject requires a gadolinium-enhanced, high-resolution MRI sequence for fusion in the treatment planning system. During treatment, patients will have daily online cone beam CT scans to apply setup corrections to ensure treatment accuracy. To ensure minimal movement during radiotherapy all subjects will be immobilized lying on their back in a plastic headshell with an integrated bite block.

For subjects in the single-fraction arm that are not requiring steroids before radiotherapy, dexamethasone 8 mg 1 hour before the radiotherapy and for 5 days afterwards is required. For subjects in the single-fraction arm that are requiring corticosteroids for symptom management before radiotherapy, dexamethasone 8 mg before treatment and 8 mg 2 times daily for 2 days is required. Beginning three days after radiotherapy, a taper back to the pre-radiotherapy dose can be done swiftly over 4-6 days. However, for subjects who have been on dexamethasone for more than 2 weeks at this time point, slow tapering from the pre-radiotherapy dose using decrements of 0.5 - 2 mg every 3-5 days should be used to prevent a hypocortisolemia. For subjects in the 5-fraction arm, corticosteroids will be prescribed according to the preference of the treating radiation oncologist. Anti-sickness medication and steroids will be prescribed are required before each fraction in both arms.

Following therapy completion, all patients will be seen at 6 weeks, 3, 6, 9 and 12 months. At each visit history and neurological examination will be performed. Cognitive Function, Karnofsky Performance Status, Quality of life and Adverse Events will all be assessed and recorded. Activities of Daily Living and steroid use will be assessed by telephone consultation every 4 weeks (monthly) for 1 year. Steroid use will be confirmed by evaluating the pharmacy prescription database.

Patients will have contrast-enhanced MRI brain at every time point with a creatinine 1 week before each MRI to ensure safety of intravenous contrast administration. Steroid use will be recorded in a patient diary for first 6 weeks post treatment and monthly by telephone discussion.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: May 18, 2020
• Est. primary completion date: May 18, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age = 18

• Pathologically confirmed solid malignancy

• 1-10 brain or brainstem metastases on MRI with a maximum of 4 cm diameter

• Documented extracranial disease

• Anticipated median survival 3-6 months (Graded Prognostic Assessment: Appendix I)

• Available for regular clinical and imaging follow up (< 1 hour from a cancer centre)

• Montreal Cognitive Assessment score = 20 (Appendix II)

• Karnofsky Performance Score (KPS) = 70 (Appendix III)

• Barthel Activities of Daily Living score = 90 (Appendix IV)

• Able to complete EORTC quality of life questionnaires (Appendix V)

Exclusion Criteria:

• A metastasis located within 5 mm of the optic nerves or optic chiasm

• Requiring craniotomy to relieve mass effect

• Cytotoxic systemic therapy administered within one week before radiotherapy or planned within one week after radiotherapy

• Neurological decline since starting corticosteroids

• Metastatic germinoma, small cell carcinoma, multiple myeloma, lymphoma or leukaemia

• Systemic lupus erythematosis, scleroderma, or other connective tissue disorders not in remission

• Multiple sclerosis

• Glomerular Filtration Rate < 45 ml/minute

• Contra-indications to MRI

• Pregnancy

• AST, ALT or Bilirubin > 3 times upper limit of normal

• Haemorrhagic Metastases

Related Conditions & MeSH terms

• Brain Metastases
• Brain Neoplasms
• Neoplasm Metastasis

Intervention

Radiation:
• Single-fraction radiotherapy
Volumetric modulated arc therapy (VMAT) delivering 15 Gy in one fraction to brain metastases
• Whole-brain radiotherapy
Whole brain radiotherapy delivering 20 Gy in five fractions to brain metastases

Locations

Country	Name	City	State
Canada	British Columbia Cancer Agency	Vancouver	British Columbia

Sponsors (1)

Lead Sponsor	Collaborator
British Columbia Cancer Agency

Country where clinical trial is conducted

Canada, 

References & Publications (20)

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* Note: There are 20 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Compare the use of corticosteroids	The subjects' use of corticosteroids will be recorded in a diary for the first 6 weeks and assessed monthly with phone follow-up. The amount and pattern of corticosteroid use will be compared between the two arms of the study.	Every 4 weeks for 1 year
Other	Compare the incidence of retreatment with cranial radiotherapy	Subjects with new brain metastases can be treated in a number of ways if their performance status remains good. If 3 months have passed since their initial treatment and there are 1-10 new metastases, subjects can receive the study treatment with 15 Gy in 1 fraction again. However, if the new brain metastases are detected within 3 months or there are more than 10 new brain metastases, subjects must have WBRT, rather than treatment to the metastases alone. Subjects with progression or relapse of a treated brain metastasis can be considered for surgery, retreatment with radiosurgery or retreatment with WBRT. Subjects with poor performance status should be considered for best supportive care.	3 months
Other	Compare the incidence of acute and late side effects	The study will use the descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) for grading of acute and late side effects. The incidence of the various side effects will be compared between the two arms.	6 weeks, 3 months, 6 months, 9 months, 12 months
Other	Compare the time to decline in activities of daily living using the Modified Barthel Index	The Modified Barthel index will be administered at baseline and at each follow-up visit. The scores will be recorded and analysed. The minimum clinically important difference for this scale is 10 points.	Every 4 weeks for 1 year
Other	Compare the time to decline in Karnofsky Performance Status < 70	The KPS will be recorded at each clinic visit. The patient will be regarded as having had a decline in KPS when it falls below 70, at which time subjects are no longer independent.	6 weeks, 3 months, 6 months, 9 months, 12 months
Other	Compare the time to decline in cognition	The MoCA questionnaire will be administered at baseline and at each follow-up visit (Appendix II). The score will be recorded and analysed. A decline in MOCA score of 3 is considered to be clinically significant.	6 weeks, 3 months, 6 months, 9 months, 12 months
Other	Time to decline in quality of life	The EORTC QLQ-PAL-15 will be administered at baseline and at each follow-up visit. The EORTC BN-20 (brain-specific) quality of life questionnaire will be administered at baseline and at each follow-up visit. The quality of life questionnaire scores will be recorded and analysed.	6 weeks, 3 months, 6 months, 9 months, 12 months
Primary	Accrual	The time of accrual of 20 subjects will be recorded in months from the official study opening at each cancer centre until the 20th patient is accrued. The rate of accrual will be calculated by dividing the number of patients by the number of months it took to accrue them	8 months
Secondary	Intracranial disease control	All subjects who complete radiotherapy and have imaging at 6 weeks will be considered evaluable for response. Those who exhibit objective disease progression on imaging before 6 weeks will also be considered evaluable for response.	3 months