Local Consolidative Radiation Therapy Plus TKI Versus TKI Alone in Driver Mutated OM-NSCLC

Study Overview
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Brief Summary
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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.

Detailed Description
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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

Official Title
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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

Conditions
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Oligometastatic Disease, Non-small Cell Lung Cancer, Driver Mutation

Intervention / Treatment
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* Radiation: Local Consolidative Radiation Therapy
* Drug: TKI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with pathologically proven diagnosis of NSCLC Patients with positive oncogene driver mutation (EGFR or ALK/ROS) Patients who have received at least 2-4 months of TKI therapy without progression 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) Patients suitable for local consolidative therapy 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); Patients with ECOG performance status of 0-2 Age > 18 years For females of child-bearing potential, negative serum or urine pregnancy test within 14 days prior to study registration Exclusion Criteria: Patients with progressive disease after 2-3 months of initial TKI therapy Patients with negative oncogene driver mutations (EGFR/ALK/ROS) Patients not suitable for local consolidative radiation therapy Patients who are not suitable for further continuation of TKI therapy due to toxicity 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; Patients with prior history of radiation therapy to thorax Patients with second malignancy (Synchronous or Metachronous) Pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Open-label, parallel-group RCT
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm 1: Continuation of TKI therapy alone<br>Patients in this arm will continue to receive standard treatment of TKI alone | Drug: TKI<br>* TKI<br>|
| Experimental: Arm 2: Continuation of TKI therapy + Local Consolidative Radiation therapy to 1-5 sites<br>Patients will receive local consolidate radiation therapy to all oligo-metastatic sites plus radiation therapy to primary disease in addition to TKI | Radiation: Local Consolidative Radiation Therapy<br>* Local consolidative radiation therapy to loco-regional disease and all Oligometastatic sites in addition to TKI<br>Drug: TKI<br>* TKI<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Oligometastatic NSCLC, Driver mutation, TKI, Local consolidative therapy, SABR, Oligometastases