Stereotactic Radiosurgery vs Whole Brain Radiotherapy in Breast Cancer With Brain Oligometastasis

NCT ID: NCT05144867

Last Updated: 2023-10-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

98 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-08-31

Study Completion Date

2024-03-31

Brief Summary

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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.

Detailed Description

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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 5 brain metastases, each with a maximum diameter of no more than 3.5 cm on contrast enhanced magnetic resonance imaging(MRI) scans.

Exclusion criteria

* Serious medical comorbidities
* ECOG \>= 2
* Prior Brain Radiotherapy
* \>5 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 using the 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.

Conditions

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Breast Cancer Brain Metastases, Adult Stereotactic Radiosurgery Whole Brain Radiotherapy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type ACTIVE_COMPARATOR

Stereotactic Radiosurgery

Intervention Type RADIATION

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.

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.

Group Type EXPERIMENTAL

Stereotactic Radiosurgery

Intervention Type RADIATION

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.

Interventions

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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.

Intervention Type RADIATION

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Post Graduate Institute of Medical Education and Research, Chandigarh

OTHER

Sponsor Role lead

Responsible Party

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Dr Budhi Singh Yadav

Additional Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Budhi Singh Yadav, MD

Role: PRINCIPAL_INVESTIGATOR

PGIMER, Chandigarh

Locations

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Budhi Singh Yadav

Chandigarh, , India

Site Status RECRUITING

Countries

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India

Central Contacts

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Budhi Singh Yadav, MD

Role: CONTACT

Budhi Singh Yadav, MD

Role: CONTACT

0172275 ext. 6390

Facility Contacts

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BUDHI SINGH S YADAV, MD

Role: primary

9815981176

References

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Gupta A, Yadav BS, Ballari N, et al. LINAC-based stereotactic radiosurgery/radiotherapy for brain metastases in patients with breast cancer. Journal of Radiotherapy in Practice , Volume 21 , Issue 3 , September 2022 , pp. 351 - 359 DOI: https://doi.org/10.1017/S1460396921000029[Opens in a new window]

Reference Type BACKGROUND

Yadav BS, Vias P, Robert N, Gade VKV, Kajla A. Whole Brain Radiotherapy Versus Stereotactic Radiosurgery in Breast Cancer Patients With Brain Metastases-A Phase 3 Open Label Randomized Study. Asia Pac J Clin Oncol. 2025 Sep 22. doi: 10.1111/ajco.70029. Online ahead of print.

Reference Type DERIVED
PMID: 40983872 (View on PubMed)

Other Identifiers

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NK/7784/Study/249

Identifier Type: -

Identifier Source: org_study_id

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