Local Consolidative Radiation Therapy Plus TKI Versus TKI Alone in Driver Mutated OM-NSCLC (TARGET-01)

A Phase II Randomized Controlled Trial of TKI Alone Versus TKI and Local Consolidative Radiation Therapy in Oncogene Driver Mutated Oligo Metastatic Non Small Cell Lung Cancer Patients

A Phase II randomized controlled trial of TKI Alone versus TKI and Local Consolidative Radiation Therapy in oncogene driver mutated oligo metastatic Non-small cell lung cancer patients.

Study Overview

• Status: Recruiting
• Conditions: Non-small Cell Lung Cancer; Oligometastatic Disease; Driver Mutation
• Intervention / Treatment: Drug: TKI; Radiation: Local Consolidative Radiation Therapy

Detailed Description

Randomization Arms: Eligible patients will be randomized in 1:1 ratio to TKI alone or TKI + LCRT. This will be an intention to treat randomized study.

Arm 1: Continuation of TKI therapy alone Arm 2: Continuation of TKI therapy + Local Consolidative Radiation therapy to loc0-regional disease and 1-5 oligometastatic sites

• Study Type: Interventional
• Enrollment (Estimated): 106
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Dr. Anil Tibdewal, MD; Phone Number: 7030 91-22-24177000; Email: aniltibdewal@gmail.com
• Study Contact Backup: Name: Dr. Jai Prakash Agarwal, MD; Phone Number: 6791 91-22-24177000; Email: agarwaljp@tmc.gov.in

Study Locations

• India
  • Maharashtra
    • Mumbai, Maharashtra, India, 400012
      • Recruiting
      • Tata Memorial Hospital
      • Principal Investigator: Dr. Anil Tibdewal, MD
      • Contact: Dr. Anil Tibdewal, MD; Phone Number: 7030 022-24177000; 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. Patients with pathologically proven diagnosis of NSCLC
2. Patients with positive oncogene driver mutation (EGFR or ALK/ROS)
3. Patients who have received at least 2-4 months of TKI therapy without progression
4. Patients with 1-5 sites of metastatic disease not including the primary tumor and regional nodes (less than 3 metastatic lesions in one organ will be eligible and 4 or more metastatic lesions in one organ will be ineligible)
5. Patients suitable for local consolidative therapy

6. Adequate end-organ function CBC/differential obtained within 15 days prior to registration on study, with adequate bone marrow function defined as follows:

   • Absolute neutrophil count (ANC) ≥ 500 cells/mm3;
   • Platelets ≥ 50,000 cells/mm3;
   • Hemoglobin ≥ 8.0 g/dl (Use of transfusion or other intervention to achieve Hgb ≥ 8.0 g/dl is acceptable);
7. Patients with ECOG performance status of 0-2
8. Age > 18 years
9. For females of child-bearing potential, negative serum or urine pregnancy test within 14 days prior to study registration

Exclusion Criteria:

1. Patients with progressive disease after 2-3 months of initial TKI therapy
2. Patients with negative oncogene driver mutations (EGFR/ALK/ROS)
3. Patients not suitable for local consolidative radiation therapy
4. Patients who are not suitable for further continuation of TKI therapy due to toxicity

5. Severe, active co-morbidity defined as follows:

   • Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months;
   • Transmural myocardial infarction within the last 6 months;
   • Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration;
6. Patients with prior history of radiation therapy to thorax
7. Patients with second malignancy (Synchronous or Metachronous)
8. Pregnancy

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: Arm 1: Continuation of TKI therapy alone; Patients in this arm will continue to receive standard treatment of TKI alone	Drug: TKI; TKI
Experimental: Arm 2: Continuation of TKI therapy + Local Consolidative Radiation therapy to 1-5 sites; Patients will receive local consolidate radiation therapy to all oligo-metastatic sites plus radiation therapy to primary disease in addition to TKI	Drug: TKI; TKI; Radiation: Local Consolidative Radiation Therapy; Local consolidative radiation therapy to loco-regional disease and all Oligometastatic sites in addition to TKI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	Progression Free Survival will be defined as the time from the date of randomization until the date of disease recurrence or progression is documented, or until death in the absence of recurrence, whichever is earlier.	Upto 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	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 2 years
Local control rates	Local control will be defined as the lack of progressive disease at the treated sites (complete response, partial response and stable disease).	Upto 2 years
Health Related Quality of Life using the EORTC-QLQ-C30 questionnaire	Quality of life will be assessed for each arm	From time of randomization to time of death or up to 24 months
Health Related Quality of Life using the EORTC-LC13 questionnaire	Quality of life will be assessed for each arm	From time of randomization to time of death or up to 24 months
Toxicities using CTC v5.0 (radiotherapy related)	Toxicity will be defined as per the common terminology criteria version 5.0 at baseline and at subsequent follow up till 2 years	From time of Randomization to time of death or up to 24 months

Collaborators and Investigators

• Sponsor: Tata Memorial Hospital
• Investigators: Principal Investigator: Dr. Anil Tibdewal, MD, Tata Memorial Hospital, Parel, Mumbai, Maharashtra, India

Publications and helpful links

General Publications

• Tibdewal A, Agarwal J, Mummudi N, Noronha V, Prabhash K, Patil V, Purandare N, Janu A, Kaushal R, Kannan S. Protocol for a phase II randomised controlled trial of TKI alone versus TKI and local consolidative radiation therapy in patients with oncogene driver-mutated oligometastatic non-small cell lung cancer. BMJ Open. 2021 Feb 15;11(2):e041345. doi: 10.1136/bmjopen-2020-041345.

Study record dates

Study Major Dates

• Study Start (Actual): November 11, 2019
• Primary Completion (Estimated): November 11, 2026
• Study Completion (Estimated): November 11, 2027

Study Registration Dates

• First Submitted: February 22, 2022
• First Submitted That Met QC Criteria: March 11, 2022
• First Posted (Actual): March 14, 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: Oligometastases; TKI; SABR; Oligometastatic NSCLC; Driver mutation; Local consolidative therapy
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: 3338; CTRI/2019/11/021872 (Registry Identifier: Clinical Trial Registry of India)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Protocol manuscript is 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