search
Back to results

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

Primary Purpose

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

Status
Recruiting
Phase
Phase 3
Locations
India
Study Type
Interventional
Intervention
Stereotactic radiosurgery/whole brain radiotherapy
Tyrosine kinase inhibitor
Sponsored by
Tata Memorial Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Asymptomatic Brain Metastases focused on measuring Asymptomatic brain metastases, EGFR mutation, Whole brain radiotherapy, Stereotactic radiosurgery, ALK rearrangement

Eligibility Criteria

18 Years - 99 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Tata Memorial HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Upfront Cranial Radiotherapy

Observation (Delayed Cranial Radiotherapy)

Arm Description

Stereotactic radiosurgery or Whole brain radiotherapy upfront in asymptomatic brain metastases

Observation (Delayed Cranial radiotherapy) of Asymptomatic brain metastases

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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.
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.
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
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
Local Control

Full Information

First Posted
February 1, 2022
Last Updated
April 11, 2023
Sponsor
Tata Memorial Hospital
search

1. Study Identification

Unique Protocol Identification Number
NCT05236946
Brief Title
Observation or Upfront Cranial RT in Oncogene Mutated NSCLC With Asymptomatic BM: A Phase III RCT
Official Title
Observation or Upfront Cranial RT in Oncogene Driver Mutated NSCLC With Asymptomatic Brain Metastases: A Phase III Randomized Controlled Trial
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 10, 2020 (Actual)
Primary Completion Date
July 2024 (Anticipated)
Study Completion Date
July 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Tata Memorial Hospital

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Asymptomatic Brain Metastases, Driver Mutation Positive Non-small Cell Lung Cancer
Keywords
Asymptomatic brain metastases, EGFR mutation, Whole brain radiotherapy, Stereotactic radiosurgery, ALK rearrangement

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
190 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Upfront Cranial Radiotherapy
Arm Type
Active Comparator
Arm Description
Stereotactic radiosurgery or Whole brain radiotherapy upfront in asymptomatic brain metastases
Arm Title
Observation (Delayed Cranial Radiotherapy)
Arm Type
Experimental
Arm Description
Observation (Delayed Cranial radiotherapy) of Asymptomatic brain metastases
Intervention Type
Radiation
Intervention Name(s)
Stereotactic radiosurgery/whole brain radiotherapy
Intervention Description
SRS/ WBRT for asymptomatic brain metastases depending on the number of brain metastases
Intervention Type
Drug
Intervention Name(s)
Tyrosine kinase inhibitor
Intervention Description
TKI
Primary Outcome Measure Information:
Title
Intracranial progression free survival at 24 months
Description
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
Time Frame
2 year
Secondary Outcome Measure Information:
Title
Overall Survival
Description
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.
Time Frame
Upto 5-year
Title
Progression free survival
Description
Progression free survival will be defined from the date of randomization to the date of progression or the date of death whichever is earlier.
Time Frame
upto 2 year
Title
Neurocognition toxicity
Description
Neuro-cognition assessment will be done using HVLT-R (Total Recall) at baseline and at 3, 6 and 12 months for assessable patients
Time Frame
Upto 12 months
Title
Toxicity using CTC v5.1
Description
Toxicity assessment will be defined as per the common terminology criteria version 5.0 at baseline and at subsequent follow up till 2 years
Time Frame
Upto 2 years
Title
Local Control
Time Frame
Upto 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Anil Tibdewal, MD
Phone
9122 2417 7000
Ext
7030
Email
aniltibdewal@gmail.com
Facility Information:
Facility Name
Tata Memorial Hospital
City
Mumbai
State/Province
Maharashtra
ZIP/Postal Code
400012
Country
India
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dr. Anil Tibdewal, MD
Email
aniltibdewal@gmail.com
First Name & Middle Initial & Last Name & Degree
Dr. Anil Tibdewal, MD

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
Protocol manuscript will be published and the results will be published in international peer-reviewed journal

Learn more about this trial

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

We'll reach out to this number within 24 hrs