TARGET-02: Standard Maintenance Therapy (SMT) vs Local Consolidative Radiation Therapy and SMT in OM-NSCLC

Sponsor

Tata Memorial Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT05278052

Collaborator

(none)

190

Enrollment

Location

Arms

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Oligometastatic Disease Metastatic Non Small Cell Lung Cancer	Radiation: Local consolidative radiation therapy Drug: Standard maintenance therapy as decided by the treating medical oncologist	Phase 3

Detailed Description

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

Study Design

Study Type:

Interventional

Anticipated Enrollment :

190 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Phase III, Open-label, Randomized controlled trial,Phase III, Open-label, Randomized controlled trial,

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Apr 20, 2020

Anticipated Primary Completion Date :

Apr 20, 2026

Anticipated Study Completion Date :

Apr 20, 2028

Arms and Interventions

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

Arm

Intervention/Treatment

Active Comparator: ARM A: Standard maintenance therapy alone

Maintenance systemic therapy/ observation

Drug: Standard maintenance therapy as decided by the treating medical oncologist

Standard maintenance therapy/Observation

Experimental: ARM B: Local consolidative radiation therapy (LCRT)

Radiation therapy to all oligometastatic sites including primary loco-regional disease

Radiation: Local consolidative radiation therapy

Local consolidative radiation therapy (LCRT) to all oligo-metastatic sites in addition to primary disease site

Other Names:

LCRT

Drug: Standard maintenance therapy as decided by the treating medical oncologist

Standard maintenance therapy/Observation

Outcome Measures

Primary Outcome Measures

Overall survival (OS) [Upto 2 years]
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.

Secondary Outcome Measures

Progression free survival (PFS ) [Upto 2 years]
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.
Local control rates of treated sites [Upto 2 years]
Local control rate will be defined as the absence of progressive disease at the treated sites
New distant metastases [Upto 2 years]
Time to onset of new distant metastases
Health Related QOL using the EORTC-QLQ-C30 questionnaire [From randomization every 3 months till 2 years]
To evaluate patient reported outcomes between the two arms
Health Related QOL using the EORTC- LC13 questionnaire [From randomization every 3 months till 2 years]
To evaluate patient reported outcomes between the two arms
Response rates [From randomization every 3 months upto 2 years]
To compare response rates between the two arms
Toxicity using CTC v5.0 (radiotherapy related acute and late toxicity) [Upto 2 years]
Toxicity assessment will be defined as per the common terminology criteria version 5.0 at baseline and at subsequent follow up till 2 years

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 99 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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