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

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

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 Overview

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

• Study Type: Interventional
• Enrollment (Estimated): 190
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Anil Tibdewal, MD; Phone Number: 7030 9122 2417 7000; Email: aniltibdewal@gmail.com

Study Locations

• India
  • Maharashtra
    • Mumbai, Maharashtra, India, 400012
      • Recruiting
      • Tata Memorial Hospital
      • Principal Investigator: Dr. Anil Tibdewal, MD
      • Contact: Dr. Anil Tibdewal, MD; Email: aniltibdewal@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	2 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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	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	Upto 2 years
Local Control		Upto 2 years

Collaborators and Investigators

• Sponsor: Tata Memorial Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 10, 2020
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: February 1, 2022
• First Submitted That Met QC Criteria: February 2, 2022
• First Posted (Actual): February 11, 2022

Study Record Updates

• Last Update Posted (Estimated): September 10, 2025
• Last Update Submitted That Met QC Criteria: September 3, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Stereotactic radiosurgery; EGFR mutation; ALK rearrangement; Whole brain radiotherapy; Asymptomatic brain metastases
• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms; Neoplasms by Site; Neoplastic Processes; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasm Metastasis; Brain Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Investigative Techniques; Therapeutics; Surgical Procedures, Operative; Pharmacologic Actions; Chemical Actions and Uses; Radiotherapy; Stereotaxic Techniques; Neurosurgical Procedures; Tyrosine Kinase Inhibitors; Radiosurgery
• Other Study ID Numbers: CTRI/2020/08/027279; IEC/3470 (Other Identifier: Tata Memorial Hospital)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Protocol manuscript will be published and the results will be published in international peer-reviewed journal

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No