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

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

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

Study Overview

• Status: Recruiting
• Conditions: Oligometastatic Disease; Metastatic Non Small Cell Lung Cancer
• Intervention / Treatment: Drug: Standard maintenance therapy as decided by the treating medical oncologist; Radiation: Local consolidative radiation therapy

Detailed Description

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

• Study Type: Interventional
• Enrollment (Anticipated): 190
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Dr. Anil Tibdewal; Phone Number: 7030 +91-22-24177000; Email: aniltibdewal@gmail.com
• Study Contact Backup: Name: Dr. Jai Prakash Agarwal; Phone Number: 6791 +91-22-24177000; Email: agarwaljp@tmc.gov.in

Study Locations

• India
  • Maharashtra
    • Mumbai, Maharashtra, India, 400012
      • Recruiting
      • Tata Memorial Hospital, Parel
      • Contact: Dr. Anil Tibdewal, MD; Phone Number: 7030 +91-22-24177000; Email: aniltibdewal@gmail.com
      • Principal Investigator: Dr. Anil Tibdewal, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age > 18 years
2. Patients with ECOG performance status of 0-2
3. Patients with pathologically proven diagnosis of NSCLC
4. 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)
5. Patients who have received standard duration of systemic therapy (4 - 6 cycles) without progression of the disease
6. Patients suitable for definitive therapy to the primary disease
7. 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.
8. 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.
9. 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.
10. 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.

11. 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);
12. For females of child-bearing potential, negative serum or urine pregnancy test within 14 days prior to study registration;
13. Patients willing for written informed consent and must be willing to comply with the specified follow up schedule

Exclusion Criteria:

1. Patients with progressive disease after initial standard systemic therapy
2. Patients with oncogene driver mutations
3. Patients with more than 5 sites of oligo metastases
4. Patients with metastatic lesion size of more than 5 cm
5. Patients with more than three metastatic lesion in one organ
6. Patients not suitable for definitive radiation therapy to primary disease
7. Patients not suitable for ablative radiation therapy to metastatic sites
8. Patients with malignant peritoneal disease
9. Patients with malignant pleural effusion
10. Leptomeningeal disease
11. Brain metastases in the brain stem
12. Clinical or radiological evidence of spinal cord compression or metastases within 2 mm of spinal cord on MRI

13. 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;
14. Patients with prior history of radiation therapy to thorax
15. Patients with previous history of malignancy within last 3 years from the date of diagnosis
16. Pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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	Drug: Standard maintenance therapy as decided by the treating medical oncologist; Standard maintenance therapy/Observation; Radiation: Local consolidative radiation therapy; Local consolidative radiation therapy (LCRT) to all oligo-metastatic sites in addition to primary disease site; Other Names: LCRT

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Tata Memorial Hospital
• Investigators: Principal Investigator: Dr. Anil Tibdewal, Tata Memorial Hospital, Parel, Mumbai, Maharashtra, India

Publications and helpful links

General Publications

• Tibdewal A, Agarwal JP, Srinivasan S, Mummudi N, Noronha V, Prabhash K, Patil V, Purandare N, Janu A, Kannan S. Standard maintenance therapy versus local consolidative radiation therapy and standard maintenance therapy in 1-5 sites of oligometastatic non-small cell lung cancer: a study protocol of phase III randomised controlled trial. BMJ Open. 2021 Mar 16;11(3):e043628. doi: 10.1136/bmjopen-2020-043628.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): April 20, 2020
• Primary Completion (Anticipated): April 20, 2026
• Study Completion (Anticipated): April 20, 2028

Study Registration Dates

• First Submitted: February 22, 2022
• First Submitted That Met QC Criteria: March 11, 2022
• First Posted (Actual): March 14, 2022

Study Record Updates

• Last Update Posted (Actual): April 14, 2023
• Last Update Submitted That Met QC Criteria: April 11, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: NSCLC; Oligometastatic disease; Maintenance therapy; Local Consolidative Radiation Therapy; SABR
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: 3445; CTRI/2020/04/024761 (Registry Identifier: Clinical Trial Registry of India)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Protocol manuscript is published and the results will be published in International peer-reviewed journal

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No