Stereotactic Radiosurgery vs Whole Brain Radiotherapy in Breast Cancer With Brain Oligometastasis (SRSvsWBRT)

• ClinicalTrials.gov Identifier: NCT05144867
• Recruitment Status: Recruiting
• First Posted: December 3, 2021
• Last Update Posted: December 3, 2021
• Sponsor: Postgraduate Institute of Medical Education and Research
• Information provided by (Responsible Party): Dr Budhi Singh Yadav, Postgraduate Institute of Medical Education and Research

Study Description

Brief Summary:

This trial aims to assess the impact of SRS on overall survival, PFS, radiation toxicity and quality of life as compared to WBRT in oligometastatic brain disease in breast cancer patients. Total 98 patients with breast cancer with brain oligo-metastases will be included. The WBRT dosage schedule will be 30 Gy in 10 fractions over 2 weeks. For tumors with 2cm, SRS dose of 22 to 25 Gy will be delivered and tumor larger than 2 cm will be treated with doses of 18 to 20 Gy.

Condition or disease	Intervention/treatment	Phase
Breast Cancer; Brain Metastases, Adult; Stereotactic Radiosurgery; Whole Brain Radiotherapy	Radiation: Stereotactic Radiosurgery	Phase 3

Detailed Description:

AIMS AND OBJECTIVES To assess the impact of SRS on overall survival, brain tumour recurrence and radiation toxicity with oligometastatic brain metastasis as compared to patients who receive WBRT.

Primary End Point: Overall Survival (OS) Secondary End Points: Progression Free Survival (PFS) Toxic Effects of Radiation Quality of Life DETAILED RESEARCH METHODOLOGY Study Setting: Department of Radiotherapy and Oncology, Post Graduate Institute of Medical Education and Research, Chandigarh Study Design: Prospective hospital based study

Inclusion criteria:

• Age >=18 years
• Willing to provide informed consent
• Histologically confirmed malignancy with metastatic disease detected on imaging.
• ECOG performance status 0-1
• 1 to 3 brain metastases, each with a maximum diameter of no more than 3 cm on contrast enhanced magnetic resonance imaging(MRI) scans.

Exclusion criteria

• Serious medical comorbidities
• ECOG >= 2
• Prior Brain Radiotherapy
• >3 brain metastasis
• Maximum diameter >4cm on MRI

Randomisation and Treatment:

Prior to randomization, a complete history and physical examination by the treating radiation oncologist will be done. Histologically confirmation of malignancy is required, with metastatic disease detected on imaging. Prior to randomization, the patients will be stratified based on number of brain metastases (single vs 2-3), extent of extracranial disease (active vs stable). Extracranial disease will be considered to be stable when the tumor had been clinically controlled for 6 months or longer prior to the detection of brain metastases. After informed consent, eligible patients will be randomised in two arms.

Arm 1:

The WBRT dosage schedule will be 30 Gy in 10 fractions over 2 weeks. For Arm 1, Treatment planning is to be done using CT simulation or conventional simulation (fluoroscopy). Simple beam arrangements, such as parallel opposed beams, will be favoured wherever possible.

Arm 2:

All patients in Arm 2 will undergo planning CT simulation with 1mm slice thickness. For all lesions, the gross tumor volume (GTV) will be defined as the visible tumor on CT and/or MRI imaging. A Planning Target Volume (PTV) margin of 2-5 mm will be added. Organs at risk visible in the planning CT scan will be contoured. The doses will be prescribed to approximately 100% isodose level and 95% of the PTV should receive 95% of the prescription dose. Metastases with a maximum diameter of up to 2 cm will be treated with doses of 22 to 25 Gy and those larger than 2 cm will be treated with doses of 18 to 20 Gy.

Follow up:

Clinical evaluations and MRI scans will be done 1 and 3 months after treatment and every 3 months thereafter. In cases in which a recurrence will be detected, further treatment can be administered. The size of the treated lesions will be measured in 3 dimensions, and this size, the development of new brain metastases, and the development of leukoencephalopathy associated with radiological findings (according to the National Cancer Institute's Common Toxicity Criteria version 4.0319) will be scored based on serial MRI scans. Overall survival will be measured as time until death from any cause, and progression-free survival as time to either progression or death, whichever occurs first. Lesion response will be evaluated in this study using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee20. At each visit, functional status and neurologic toxic effects will be scored. Systemic functional status will be evaluated by using the KPS score. Neurologic function will be evaluated according to the criteria listed21.

Statistical analysis:

This study will aim to detect an improvement in overall survival. The study will therefore be designed with 80% power. It is estimated that the median survival of the control group after randomization in this study will be 9 months. In order to detect a 6-month improvement in median survival from 9 months to 15 months with SRS, a total of 93 patients will be needed. Assuming a 5% rate of loss to follow up, a total of 98 patients will be accrued. The study projects accrual over 48 months with 12 months of additional follow-up. Survival will be calculated using the Kaplan-Meier method with differences compared using the stratified log-rank test. A Cox multivariable regression analysis will be used to determine baseline factors predictive of survival. Differences in rates of grade 2 or higher toxicity between groups will be tested usingthe Fisher's Exact Test. Differences in progression free survival will be tested using the stratified log-rank test.

Novelty of study: This trial aims to assess the impact of SRS on overall survival, PFS, radiation toxicity and quality of life as compared to WBRT in oligometastatic brain disease in breast cancer patients. It may lead to better understanding of role of SRS in oligometastatic paradigm.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 98 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Stereotactic Radiosurgery vs Whole Brain Radiotherapy in Breast Cancer With Brain Oligometastasis- A Randomised Controlled Phase 3 Trial
• Actual Study Start Date: August 31, 2021
• Estimated Primary Completion Date: August 31, 2025
• Estimated Study Completion Date: August 31, 2026

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Arm 1; The WBRT dosage schedule will be 30 Gy in 10 fractions over 2 weeks. For Arm 1, Treatment planning is to be done using CT simulation or conventional simulation (fluoroscopy). Simple beam arrangements, such as parallel opposed beams, will be favoured wherever possible.	Radiation: Stereotactic Radiosurgery; All patients to undergo planning CT simulation with 1mm slice thickness. For all lesions, the gross tumor volume (GTV) will be defined as the visible tumor on CT and/or MRI imaging. A Planning Target Volume (PTV) margin of 2-5 mm will be added. Organs at risk visible in the planning CT scan will be contoured. The doses will be prescribed to approximately 100% isodose level and 95% of the PTV should receive 95% of the prescription dose. Metastases with a maximum diameter of up to 2 cm will be treated with doses of 22 to 25 Gy and those larger than 2 cm will be treated with doses of 18 to 20 Gy.
Experimental: Arm 2; Metastases with a maximum diameter of up to 2 cm will be treated with doses of 22 to 25 Gy and those larger than 2 cm will be treated with doses of 18 to 20 Gy.	Radiation: Stereotactic Radiosurgery; All patients to undergo planning CT simulation with 1mm slice thickness. For all lesions, the gross tumor volume (GTV) will be defined as the visible tumor on CT and/or MRI imaging. A Planning Target Volume (PTV) margin of 2-5 mm will be added. Organs at risk visible in the planning CT scan will be contoured. The doses will be prescribed to approximately 100% isodose level and 95% of the PTV should receive 95% of the prescription dose. Metastases with a maximum diameter of up to 2 cm will be treated with doses of 22 to 25 Gy and those larger than 2 cm will be treated with doses of 18 to 20 Gy.

Outcome Measures

Primary Outcome Measures :

1. Overall survival [ Time Frame: 1 year ]
   From date of randomization till death due to breast cancer

Secondary Outcome Measures :

1. Progression Free Survival (PFS) [ Time Frame: 1 year ]
   From completion of radiotherapy treatment to intracranial progression of disease on MRI/CT scan as per the RECIST criteria which is >20% increase(>5mm absolute increase) in the the sum of the longest diameters in comparison with the smallest sum of the longest diameters recorded since treatment started.
2. Quality of Life - KPS [ Time Frame: Base line and 6 months ]
   At each visit, functional status and neurologic toxic effects will be scored. Systemic functional status will be evaluated by using the KPS score. KPS will be scored 80-100 if the patient is able to carry on normal activity and to work without special care. A score of 50-70 will indicate patient is unable to work; live at home and care for most personnel needs; varying amount of assistance required. A score of 10-30 indicate that unable to care for self; requires equivalent of hospital or institutional care; disease may be progressing rapidly. A score of 0 means patient is dead. Neurologic function will be evaluated according to the MINI MENTAL STATE EXAMINATION. Patients will be scored for each question from 0-30. Degree of impairment will be graded as severe if the score is 0-10, moderate if the score is 10-20, mild between 20-25 and questionable significant if the score is 25-30.
3. Quality of life - MINI MENTAL STATE [ Time Frame: Base line and 6 months ]
   Neurologic function will be evaluated according to the MINI MENTAL STATE EXAMINATION. Patients will be asked a set of questions( for example what is the year? season? date? day? month?; where are we now? state? county? town? city? hospital?; spell WORLD back word or count D-L-R-O-W or count back word from 100 by seven- 93, 86, 79, 72, 65). Score 1 point for each correct response with in each question will be given so that a score from 0-30 is recorded. Degree of impairment will be graded as severe if the score is 0-10, moderate if the score is 10-20, mild between 20-25 and questionable significant if the score is 25-30.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Age >=18 years
• Willing to provide informed consent
• Histologically confirmed malignancy with metastatic disease detected on imaging.
• ECOG performance status 0-1
• 1 to 3 brain metastases, each with a maximum diameter of no more than 3 cm on contrast enhanced magnetic resonance imaging(MRI) scans

Exclusion Criteria:

• Serious medical comorbidities
• ECOG >= 2
• Prior Brain Radiotherapy
• >3 brain metastasis
• Maximum diameter >4cm on MRI

Contacts and Locations

Locations

India

Budhi Singh Yadav; Recruiting

Chandigarh, India, 160012

Contact: BUDHI S YADAV 9815981176 drbudhi@gmail.com

Sponsors and Collaborators

Postgraduate Institute of Medical Education and Research

More Information

• Responsible Party: Dr Budhi Singh Yadav, Additional Professor, Postgraduate Institute of Medical Education and Research
• ClinicalTrials.gov Identifier: NCT05144867
• Other Study ID Numbers: NK/7784/Study/249
• First Posted: December 3, 2021
• Last Update Posted: December 3, 2021
• Last Verified: November 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Breast Neoplasms; Brain Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases