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

Phase 3

Recruiting

• Conditions: Driver Mutation Positive Non-small Cell Lung Cancer; Asymptomatic Brain Metastases
• Interventions: Radiation: Stereotactic radiosurgery/whole brain radiotherapy; Drug: Tyrosine kinase inhibitor

• Registration Number: NCT05236946
• Lead Sponsor: Tata Memorial Hospital

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2020-11-10
• Study First Submitted: 2022-02-01
• Study First Submitted QC: 2022-02-02
• Study First Posted: 2022-02-11
• Status Verified: 2023-04
• Last Update Submitted: 2023-04-11
• Last Update Posted: 2023-04-12
• Primary Completion: 2024-07
• Study Completion: 2026-07

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 190

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Upfront Cranial Radiotherapy	Tyrosine kinase inhibitor	Stereotactic radiosurgery or Whole brain radiotherapy upfront in asymptomatic brain metastases
Upfront Cranial Radiotherapy	Stereotactic radiosurgery/whole brain radiotherapy	Stereotactic radiosurgery or Whole brain radiotherapy upfront in asymptomatic brain metastases
Observation (Delayed Cranial Radiotherapy)	Tyrosine kinase inhibitor	Observation (Delayed Cranial radiotherapy) of Asymptomatic brain metastases

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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.
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
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.
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
Local Control	Upto 2 years

Trial Locations

Locations (1)

Tata Memorial Hospital; 🇮🇳 Mumbai, Maharashtra, India