Observation or Upfront Cranial RT in Oncogene Mutated NSCLC With Asymptomatic BM: A Phase III RCT

Sponsor

Tata Memorial Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT05236946

Collaborator

(none)

190

Enrollment

Location

Arms

67.6

Anticipated Duration (Months)

2.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Tyrosine Kinase Inhibitors (TKIs) especially higher generation TKI have higher CNS penetration rates and have shown favorable response rates in brain metastases. Brain radiotherapy/surgery is the standard treatment in brain metastases especially symptomatic metastases, however, the role of local treatment especially in driver mutation-positive non-small cell lung cancer with asymptomatic brain metastases is being questioned given their potential side effects. No randomized trial has shown the superiority of early vs delayed cranial RT in asymptomatic BM of driver mutated NSCLC.

Condition or Disease	Intervention/Treatment	Phase
Asymptomatic Brain Metastases Driver Mutation Positive Non-small Cell Lung Cancer	Radiation: Stereotactic radiosurgery/whole brain radiotherapy Drug: Tyrosine kinase inhibitor	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

190 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Observation or Upfront Cranial RT in Oncogene Driver Mutated NSCLC With Asymptomatic Brain Metastases: A Phase III Randomized Controlled Trial

Actual Study Start Date :

Nov 10, 2020

Anticipated Primary Completion Date :

Jul 1, 2024

Anticipated Study Completion Date :

Jul 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Upfront Cranial Radiotherapy Stereotactic radiosurgery or Whole brain radiotherapy upfront in asymptomatic brain metastases	Radiation: Stereotactic radiosurgery/whole brain radiotherapy SRS/ WBRT for asymptomatic brain metastases depending on the number of brain metastases Drug: Tyrosine kinase inhibitor TKI
Experimental: Observation (Delayed Cranial Radiotherapy) Observation (Delayed Cranial radiotherapy) of Asymptomatic brain metastases	Drug: Tyrosine kinase inhibitor TKI

Arm

Intervention/Treatment

Active Comparator: Upfront Cranial Radiotherapy

Stereotactic radiosurgery or Whole brain radiotherapy upfront in asymptomatic brain metastases

Radiation: Stereotactic radiosurgery/whole brain radiotherapy

SRS/ WBRT for asymptomatic brain metastases depending on the number of brain metastases

Drug: Tyrosine kinase inhibitor

TKI

Experimental: Observation (Delayed Cranial Radiotherapy)

Observation (Delayed Cranial radiotherapy) of Asymptomatic brain metastases

Drug: Tyrosine kinase inhibitor

TKI

Outcome Measures

Primary Outcome Measures

Intracranial progression free survival at 24 months [2 year]
Intracranial progression free survival will be defined as the time from the date of randomization until the date of intracranial progression is documented. Death without intracranial progression will be considered as a competing event. Intracranial response will be graded as per the Response Assessment in Neuro-Oncology (RANO) guidelines for brain metastases

Secondary Outcome Measures

Overall Survival [Upto 5-year]
Overall survival will be defined as the time from randomization until the date of death from any cause in the presence or absence of recurrence.
Progression free survival [upto 2 year]
Progression free survival will be defined from the date of randomization to the date of progression or the date of death whichever is earlier.
Neurocognition toxicity [Upto 12 months]
Neuro-cognition assessment will be done using HVLT-R (Total Recall) at baseline and at 3, 6 and 12 months for assessable patients
Toxicity using CTC v5.1 [Upto 2 years]
Toxicity assessment will be defined as per the common terminology criteria version 5.0 at baseline and at subsequent follow up till 2 years
Local Control [Upto 2 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 99 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age ≥ 18 years
Patients with ECOG performance status of 0-2
Patients with pathologically proven diagnosis of NSCLC
Patients with positive oncogene mutation status (EGFR/ALK)
Patients with radiologically confirmed parenchymal brain metastases
Patients with asymptomatic Synchronous or Metachronous brain metastases
Patients willing for written informed consent and must be willing to comply with the specified follow-up schedule