Clinical trial NCT05277844: Local Consolidative Radiation Therapy Plus TKI Versus TKI Alone in Driver Mutated OM-NSCLC
Official title: 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 type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Oligometastatic Disease
Non-small Cell Lung Cancer
Driver Mutation
Keywords: Oligometastatic NSCLC
Driver mutation
TKI
Local consolidative therapy
SABR
Oligometastases
Lead sponsor: Tata Memorial Hospital
Sponsor class: OTHER_GOV
First posted: 2022-03-14
Enrollment: 106
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Open-label, parallel-group RCT
Primary purpose: TREATMENT

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

Eligibility criteria: 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

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: Upto 2 years
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: Upto 2 years
measure: Local control rates
timeFrame: Upto 2 years
measure: Health Related Quality of Life using the EORTC-QLQ-C30 questionnaire
timeFrame: From time of randomization to time of death or up to 24 months
measure: Health Related Quality of Life using the EORTC-LC13 questionnaire
timeFrame: From time of randomization to time of death or up to 24 months
measure: Toxicities using CTC v5.0 (radiotherapy related)
timeFrame: From time of Randomization to time of death or up to 24 months
Other outcomes:
Locations:
city: Mumbai
country: India
facility: Tata Memorial Hospital
state: Maharashtra
Study officials:
affiliation: Tata Memorial Hospital, Parel, Mumbai, Maharashtra, India
name: Dr. Anil Tibdewal, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.