Asymptomatic Brain Metastases, Driver Mutation Positive Non-small Cell Lung Cancer
Conditions
Keywords
Asymptomatic brain metastases, EGFR mutation, Whole brain radiotherapy, Stereotactic radiosurgery, ALK rearrangement
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.
Interventions
RADIATIONStereotactic radiosurgery/whole brain radiotherapy
SRS/ WBRT for asymptomatic brain metastases depending on the number of brain metastases
DRUGTyrosine kinase inhibitor
TKI
Sponsors
Tata Memorial Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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 |
| 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 |
| Local Control | Upto 2 years | — |
Countries
India
Contacts
Primary ContactAnil Tibdewal, MD
Outcome results
None listed