Asymptomatic Brain MetastasesPhase 3NCT05236946
Observation or Upfront Cranial RT in Oncogene Mutated NSCLC With Asymptomatic BM: A Phase III RCT
A Phase 3 study testing Stereotactic radiosurgery/whole brain radiotherapy and Tyrosine kinase inhibitor in people with Asymptomatic Brain Metastases and Driver Mutation Positive Non-small Cell Lung Cancer, run by Tata Memorial Hospital at 1 site in India.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Asymptomatic Brain Metastases, Driver Mutation Positive Non-small Cell Lung Cancer
- What is being tested?
- Stereotactic radiosurgery/whole brain radiotherapy and Tyrosine kinase inhibitor
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 190 participants
- Where
- 1 siteIndia
- Study dates
- 10 Nov 2020to Dec 2026
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
India1 site, 1 recruiting
- Recruiting
Tata Memorial Hospital
Mumbai, Maharashtra, 400012
Dr. Anil Tibdewal, MD, aniltibdewal@gmail.com
Dr. Anil Tibdewal, MD
About this study
Official title: 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.
- Being tested
- Stereotactic radiosurgery/whole brain radiotherapy, Tyrosine kinase inhibitor
- Keywords
- Asymptomatic brain metastases, EGFR mutation, Whole brain radiotherapy, Stereotactic radiosurgery, ALK rearrangement
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Stereotactic radiosurgery/whole brain radiotherapyRadiation
SRS/ WBRT for asymptomatic brain metastases depending on the number of brain metastases
Tyrosine kinase inhibitorDrug
TKI
| Study group | Role | What they receive |
|---|---|---|
| Upfront Cranial Radiotherapy | Active comparator | Stereotactic radiosurgery or Whole brain radiotherapy upfront in asymptomatic brain metastases Receives: Radiation: Stereotactic radiosurgery/whole brain radiotherapy; Drug: Tyrosine kinase inhibitor |
| Observation (Delayed Cranial Radiotherapy) | Experimental | Observation (Delayed Cranial radiotherapy) of Asymptomatic brain metastases Receives: Drug: Tyrosine kinase inhibitor |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 2 year
Secondary outcomes (5)
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.
Measured: 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.
Measured: 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
Measured: 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
Measured: Upto 2 years
Local Control
Measured: Upto 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Feb 2022
- Study start10 Nov 2020
- Primary completionDec 2025 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Asymptomatic Brain MetastasesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 190 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tata Memorial Hospital
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Anil Tibdewal, Tata Memorial Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05236946
- Sponsor's protocol ID
- CTRI/2020/08/027279
- Other IDs
- IEC/3470
- Status last verified
- Sep 2025
- First submitted
- 1 Feb 2022
- Last updated
- 10 Sep 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Protocol manuscript will be published and the results will be published in international peer-reviewed journal
Study at a glance
From the registry record, last updated by the sponsor on 10 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Observation or Upfront Cranial RT in Oncogene Driver Mutated NSCLC With Asymptomatic Brain Metastases: A Phase III Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT05236946
- Acronym / sponsor ID
- CTRI/2020/08/027279
- Keywords
- Asymptomatic brain metastases, EGFR mutation, Whole brain radiotherapy, Stereotactic radiosurgery, ALK rearrangement
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 190 participants (estimated)
- Lead sponsor
- Tata Memorial HospitalOther government
- Study start
- 10 Nov 2020 (actual)
- Primary completion
- Dec 2025 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 11 Feb 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Upfront Cranial Radiotherapy | Active comparator | Radiation: Stereotactic radiosurgery/whole brain radiotherapy, Drug: Tyrosine kinase inhibitorStereotactic radiosurgery or Whole brain radiotherapy upfront in asymptomatic brain metastases |
| Observation (Delayed Cranial Radiotherapy) | Experimental | Drug: Tyrosine kinase inhibitorObservation (Delayed Cranial radiotherapy) of Asymptomatic brain metastases |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Stereotactic radiosurgery/whole brain radiotherapySRS/ WBRT for asymptomatic brain metastases depending on the number of brain metastases | Radiation | Upfront Cranial Radiotherapy |
| Tyrosine kinase inhibitorTKI | Drug | Observation (Delayed Cranial Radiotherapy), Upfront Cranial Radiotherapy |
Primary outcome
Intracranial progression free survival at 24 months
Time frame: 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
5 secondary outcomes
Overall Survival
Time frame: Upto 5-year
Progression free survival
Time frame: upto 2 year
Neurocognition toxicity
Time frame: Upto 12 months
Toxicity using CTC v5.1
Time frame: Upto 2 years
Local Control
Time frame: Upto 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Sep 2025.
- Individual participant dataSharing planned: No. Protocol manuscript will be published and the results will be published in international peer-reviewed journal
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Stereotactic radiosurgery/whole brain radiotherapy and Tyrosine kinase inhibitor in people with Asymptomatic Brain Metastases and Driver Mutation Positive Non-small Cell Lung Cancer, run by Tata Memorial Hospital at 1 site in India.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 10 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in India. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Anil Tibdewal, MD (9122 2417 7000 ext. 7030, aniltibdewal@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Intracranial progression free survival at 24 months (time frame: 2 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Sep 2025.