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

Phase 3RecruitingNCT05236946

Tata Memorial Hospital190 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

190

Conditions

Asymptomatic Brain Metastases Driver Mutation Positive Non-small Cell Lung Cancer

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 99 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Age ≥ 18 years 2. Patients with ECOG performance status of 0-2 3. Patients with pathologically proven diagnosis of NSCLC 4. Patients with positive oncogene mutation status (EGFR/ALK) 5. Patients with radiologically confirmed parenchymal brain metastases 6. Patients with asymptomatic Synchronous or Metachronous brain metastases 7. Patients willing for written informed consent and must be willing to comply with the specified follow-up schedule Exclusion Criteria: 1. Patients with CSF dissemination only without any parenchymal brain metastases 2. Patients with brain metastases in the brain stem 3. Patients with prior history of radiation therapy to the brain 4. Patient not suitable for TKI therapy as per the medical oncologist 5. Pregnant or lactating females

Outcomes

Primary Outcomes

Intracranial progression free survival at 24 months

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

Time frame: 2 year

Secondary Outcomes

Overall Survival

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.

Time frame: Upto 5-year

Progression free survival

Progression free survival will be defined from the date of randomization to the date of progression or the date of death whichever is earlier.

Time frame: upto 2 year

Neurocognition toxicity

Neuro-cognition assessment will be done using HVLT-R (Total Recall) at baseline and at 3, 6 and 12 months for assessable patients

Time frame: Upto 12 months

Toxicity using CTC v5.1

Toxicity assessment will be defined as per the common terminology criteria version 5.0 at baseline and at subsequent follow up till 2 years

Time frame: Upto 2 years

Local Control