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

Phase 2

Recruiting

• Conditions: Driver Mutation; Non-small Cell Lung Cancer; Oligometastatic Disease
• Interventions: Radiation: Local Consolidative Radiation Therapy; Drug: TKI

• Registration Number: NCT05277844
• Lead Sponsor: Tata Memorial Hospital

Brief Summary

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

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 Timeline

• Study Start: 2019-11-11
• Study First Submitted: 2022-02-22
• Study First Submitted QC: 2022-03-11
• Study First Posted: 2022-03-14
• Status Verified: 2023-04
• Last Update Submitted: 2023-04-11
• Last Update Posted: 2023-04-12
• Primary Completion: 2023-11-11
• Study Completion: 2025-11-11

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 106

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm 2: Continuation of TKI therapy + Local Consolidative Radiation therapy to 1-5 sites	TKI	Patients will receive local consolidate radiation therapy to all oligo-metastatic sites plus radiation therapy to primary disease in addition to TKI
Arm 1: Continuation of TKI therapy alone	TKI	Patients in this arm will continue to receive standard treatment of TKI alone
Arm 2: Continuation of TKI therapy + Local Consolidative Radiation therapy to 1-5 sites	Local Consolidative Radiation Therapy	Patients will receive local consolidate radiation therapy to all oligo-metastatic sites plus radiation therapy to primary disease in addition to TKI

Primary Outcome Measures

Name	Time	Method
Progression Free Survival (PFS)	Upto 2 years	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.

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Tata Memorial Hospital; 🇮🇳 Mumbai, Maharashtra, India