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

NCT05236946 | Recruiting Phase 3 DMC

• 2 other identifiers: CTRI/2020/08/027279IEC/3470
• Study Type: interventional
• Target: 190
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

Asymptomatic brain metastases; EGFR mutation; Whole brain radiotherapy; Stereotactic radiosurgery; ALK rearrangement

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Overall Survival

  Upto 5-year

• Progression free survival

  upto 2 year

• Neurocognition toxicity

  Upto 12 months

• Toxicity using CTC v5.1

  Upto 2 years

• Local Control

  Upto 2 years

Study Arms (2)

Upfront Cranial Radiotherapy

ACTIVE COMPARATOR

Stereotactic radiosurgery or Whole brain radiotherapy upfront in asymptomatic brain metastases

Radiation: Stereotactic radiosurgery/whole brain radiotherapy; Drug: Tyrosine kinase inhibitor

Observation (Delayed Cranial Radiotherapy)

EXPERIMENTAL

Observation (Delayed Cranial radiotherapy) of Asymptomatic brain metastases

Drug: Tyrosine kinase inhibitor

Interventions

Stereotactic radiosurgery/whole brain radiotherapy RADIATION

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

Upfront Cranial Radiotherapy

Tyrosine kinase inhibitor DRUG

TKI

Observation (Delayed Cranial Radiotherapy); Upfront Cranial Radiotherapy

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Patients with CSF dissemination only without any parenchymal brain metastases
• Patients with brain metastases in the brain stem
• Patients with prior history of radiation therapy to the brain
• Patient not suitable for TKI therapy as per the medical oncologist
• Pregnant or lactating females

Sponsors & Collaborators

• Tata Memorial Hospital: lead

Study Sites (1)

Tata Memorial Hospital

Mumbai, Maharashtra, 400012, India

RECRUITING

MeSH Terms

Interventions

Radiosurgery; Tyrosine Kinase Inhibitors

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses

Central Study Contacts

Anil Tibdewal, MD

CONTACT

9122 2417 7000; aniltibdewal@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr. Anil Tibdewal, Associate Professor, Radiation Oncology

Study Record Dates

• First Submitted: February 1, 2022
• First Posted: February 11, 2022
• Study Start: November 10, 2020
• Primary Completion: December 1, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: September 10, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

IN (1)