Standard Maintenance Therapy (SMT) vs Local Consolidative Radiation Therapy and SMT in OM-NSCLC

Study Overview
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Brief Summary
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Standard Maintenance Therapy versus Local Consolidative Radiation Therapy and standard maintenance therapy in 1-5 sites of OligoMetastatic Non-small cell lung cancer (NSCLC): A Phase III Randomized Controlled Trial

Detailed Description
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Standard of care maintenance therapy alone (standard arm) versus local consolidative radiation therapy and standard of care maintenance therapy (Experimental arm)

Official Title
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Standard Maintenance Therapy Versus Local Consolidative Radiation Therapy and Standard Maintenance Therapy in 1-5 Sites of Oligometastatic Non-small Cell Lung Cancer (NSCLC): A Phase III Randomized Controlled Trial

Conditions
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Oligometastatic Disease, Metastatic Non Small Cell Lung Cancer

Intervention / Treatment
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* Radiation: Local consolidative radiation therapy
* Drug: Standard maintenance therapy as decided by the treating medical oncologist


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 18 years Patients with ECOG performance status of 0-2 Patients with pathologically proven diagnosis of NSCLC Patients with 1-5 sites of metastatic disease not including the primary tumor and regional nodes (less than or equal to 3 metastatic lesions in one organ will be eligible and 4 or more metastatic lesions in one organ will be ineligible) Patients who have received standard duration of systemic therapy (4 - 6 cycles) without progression of the disease Patients suitable for definitive therapy to the primary disease All the Oligometastases lesions should be radiologically visible and suitable for ablative doses of radiation in accordance with the dose fractionation regimens specified in the protocol. Patients who have received ablative radiation therapy or surgery or RFA for metastatic sites at presentation or during systemic therapy will be eligible provided the total number of oligometastatic sites at the time of study entry (treated site included) is less than or equal to five. Patients who have received palliative RT for symptomatic bony metastases or RFA will also be eligible provided the treated site is under control on imaging. If not controlled, could be eligible for study if further ablative doses of radiation can be delivered according to the treating physician. Patients who underwent surgical decompression, or stabilization followed by palliative radiation therapy for bony metastases will be eligible in the study provided the treated site is under control on imaging and patient has less than 5 sites of metastases at the time of study entry. 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); For females of child-bearing potential, negative serum or urine pregnancy test within 14 days prior to study registration; Patients willing for written informed consent and must be willing to comply with the specified follow up schedule Exclusion Criteria: Patients with progressive disease after initial standard systemic therapy Patients with oncogene driver mutations Patients with more than 5 sites of oligo metastases Patients with metastatic lesion size of more than 5 cm Patients with more than three metastatic lesion in one organ Patients not suitable for definitive radiation therapy to primary disease Patients not suitable for ablative radiation therapy to metastatic sites Patients with malignant peritoneal disease Patients with malignant pleural effusion Leptomeningeal disease Brain metastases in the brain stem Clinical or radiological evidence of spinal cord compression or metastases within 2 mm of spinal cord on MRI 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 previous history of malignancy within last 3 years from the date of diagnosis 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: Phase III, Open-label, Randomized controlled trial,
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ARM A: Standard maintenance therapy alone<br>Maintenance systemic therapy/ observation | Drug: Standard maintenance therapy as decided by the treating medical oncologist<br>* Standard maintenance therapy/Observation<br>|
| Experimental: ARM B: Local consolidative radiation therapy (LCRT)<br>Radiation therapy to all oligometastatic sites including primary loco-regional disease | Radiation: Local consolidative radiation therapy<br>* Local consolidative radiation therapy (LCRT) to all oligo-metastatic sites in addition to primary disease site<br>* Other names: LCRT;Drug: Standard maintenance therapy as decided by the treating medical oncologist<br>* Standard maintenance therapy/Observation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) | Overall survival is defined as the duration between the date of randomization to the date of death due to any cause or the date of last follow-up, whichever is earlier. | Upto 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival (PFS ) | Progression free survival is defined as the duration between the date of randomization to the date of first documented progression or death due to any cause or date of last follow-up, whichever is earlier. | Upto 2 years | 
| Local control rates of treated sites | Local control rate will be defined as the absence of progressive disease at the treated sites | Upto 2 years | 
| New distant metastases | Time to onset of new distant metastases | Upto 2 years | 
| Health Related QOL using the EORTC-QLQ-C30 questionnaire | To evaluate patient reported outcomes between the two arms | From randomization every 3 months till 2 years | 
| Health Related QOL using the EORTC- LC13 questionnaire | To evaluate patient reported outcomes between the two arms | From randomization every 3 months till 2 years | 
| Response rates | To compare response rates between the two arms | From randomization every 3 months upto 2 years | 
| Radiotherapy related toxicity using CTC v5.0 (radiotherapy related acute and late toxicity) | At baseline and at subsequent follow up till 2 years | Upto 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NSCLC, Local Consolidative Radiation Therapy, Oligometastatic disease, Maintenance therapy, SABR