NCT05624996|RecruitingPhase 3FDA Drug

Testing the Addition of High Dose, Targeted Radiation to the Usual Treatment for Locally-Advanced Inoperable Non-Small Cell Lung Cancer

Phase III Prospective Randomized Trial of Primary Lung Tumor Stereotactic Body Radiation Therapy Followed by Concurrent Mediastinal Chemoradiation for Locally-Advanced Non-Small Cell Lung Cancer

NRG Oncology ClinicalTrials.gov

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3 other identifiers

NRG-LU008NCI-2022-08263U10CA180868

Study Type

interventional

Target

474

Locations

2 countries

Sites

471

Timeline

RegisteredNov 2022

StartedJul 2023

CompletionOct 2031

Brief Summary

This phase III trial compares the effect of adding stereotactic body radiation therapy (SBRT) to the usual treatment (conventional image guided radiation therapy \[IGRT\] and chemotherapy followed by immunotherapy with durvalumab or targeted therapy with osimertinib) versus the usual treatment alone in treating patients with non-small cell lung cancer that has spread to nearby tissue or lymph nodes (locally advanced) and cannot be treated by surgery (inoperable). SBRT uses special equipment to position a patient and deliver radiation therapy to tumors with high precision. This method may kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. IGRT is a type of radiation therapy that creates a picture of the tumor to help guide the radiation beam during therapy, making it more accurate and causing less damage to healthy tissue. Usual chemotherapy used in this trial consists of combinations of the following drugs: cisplatin, carboplatin, paclitaxel, nab-paclitaxel, pemetrexed, and etoposide. Cisplatin and carboplatin are in a class of medications known as platinum-containing compounds. Cisplatin works by killing, stopping, or slowing the growth of tumor cells. Carboplatin works in a way similar to the anticancer drug cisplatin but may be better tolerated than cisplatin. Carboplatin works by killing, stopping, or slowing the growth of tumor cells as well. Paclitaxel is in a class of medications called antimicrotubule agents. It works by stopping the growth and spread of tumor cells. Nab-paclitaxel is an albumin-stabilized nanoparticle formulation of paclitaxel which may have fewer side effects and work better than other forms of paclitaxel. Pemetrexed is in a class of medications called antifolate antineoplastic agents. It works by blocking the action of a certain substance in the body that may help tumor cells multiply. Etoposide is in a class of medications known as podophyllotoxin derivatives. It blocks a certain enzyme needed for cell division and deoxyribonucleic acid (DNA) repair and may kill tumor cells. Immunotherapy with durvalumab can induce changes in the body's immune system and can interfere with the ability of tumor cells to grow and spread. Osimertinib is in a class of medications called kinase inhibitors. It works by blocking the action of a protein called EGFR that signals cancer cells to multiply. This helps slow or stop the spread of tumor cells. Adding SBRT to the usual treatment of IGRT with chemotherapy and immunotherapy may be more effective at treating patients with locally-advanced non-small cell lung cancer than giving the usual treatment alone.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

474

participants targeted

Target at P50-P75 for phase_3

Timeline

67mo left

Started Jul 2023

Longer than P75 for phase_3

Geographic Reach

2 countries

471 active sites

Status

recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

8.3 years study duration

Study Progress34%

Jul 2023Oct 2031

First Submitted

Initial submission to the registry

November 4, 2022

Completed

18 days until next milestone

First Posted

Study publicly available on registry

November 22, 2022

Completed

8 months until next milestone

Study Start

First participant enrolled

July 12, 2023

Completed

8.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 15, 2031

Expected

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

October 15, 2031

Last Updated

May 4, 2026

Status Verified

April 1, 2026

Enrollment Period

8.3 years

First QC Date

November 4, 2022

Last Update Submit

April 28, 2026

Conditions

Locally Advanced Lung Non-Small Cell Carcinoma Stage IIB Lung Cancer AJCC v8 Stage III Lung Cancer AJCC v8

Outcome Measures

Primary Outcomes (2)

Overall survival (OS)
Non-inferiority (NI) between arm 2 and arm 1 (reference level) will be evaluated by comparing the upper bound of the 95% confidence interval for the hazard ratio to the pre-specified NI margin. NI of arm 2 will be concluded if the upper bound of the confidence interval is equal to, or falls below, the pre-specified margin at the final analysis. When evaluating the NI of arm 2 in OS, a Cox proportional hazards (PH) model stratified by stratification factors will be used to compute the hazard ratio and associated 95% confidence interval (CI). OS rates will be estimated using the Kaplan-Meier method. If the NI of arm 2 in OS is demonstrated, the superiority of arm 1 in OS will be tested at 1-sided significance level of 0.025 using a stratified log-rank test by adjusting for stratification factors.
Time between date of randomization and date of death due to any cause, assessed up to 8 years
Progression-free survival (PFS)
The PFS analysis will be conducted using the same methods and stratification factors as the OS analysis. The superiority of arm 2 in PFS will be tested at 1-sided significance level of 0.025 using a stratified log-rank test by adjusting for stratification factors. In the event that the NI of OS is not established, statistical inference of PFS will be considered exploratory in nature only. A Cox PH model stratified by stratification factors will be used to compute the hazard ratio and associated 95% CI.
Time between date of randomization and first date of documented progression or death due to any cause, assessed up to 8 years

Secondary Outcomes (8)

Objective response rate (ORR)
Up to 8 years
Time to progression
Up to 8 years
Time to primary, locoregional, or distant failure
Up to 8 years
Changes in pulmonary function
From randomization to 6 months or 12 months
Patient reported outcomes-Common Terminology Criteria for Adverse Events (PRO-CTCAE)
At 3, 12, and 24 months
+3 more secondary outcomes

Other Outcomes (9)

Clinical outcomes
Up to 8 years
Functional mean lung dose
Up to 8 years
Incidence of toxicities
Up to 8 years
+6 more other outcomes

Study Arms (2)

Arm I (image guided RT, chemotherapy, immunotherapy)

ACTIVE COMPARATOR

Patients undergo conventional IGRT and receive usual care chemotherapy consisting of paclitaxel IV followed by carboplatin IV Q7D during radiotherapy or pemetrexed IV followed by carboplatin IV every 21 days during radiotherapy or etoposide IV on days 1 to 5 and days 29 to 33 followed by cisplatin IV on days 1, 8, 29, and 36 or pemetrexed IV followed by cisplatin IV every 21 days during radiotherapy. Patients then receive consolidation durvalumab IV every 2 or 4 weeks for up to one year or osimertinib PO QD in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and/or PET/CT during follow-up.

Drug: CarboplatinDrug: CisplatinProcedure: Computed TomographyBiological: DurvalumabDrug: EtoposideRadiation: Image Guided Radiation TherapyDrug: Nab-paclitaxelDrug: OsimertinibDrug: PaclitaxelDrug: PemetrexedProcedure: Positron Emission TomographyOther: Questionnaire Administration

Arm II (SBRT, image guided RT, chemotherapy, immunotherapy)

EXPERIMENTAL

Patients undergo SBRT and conventional IGRT and then receive standard-of-care chemotherapy consisting of paclitaxel IV followed by carboplatin IV Q7D during radiotherapy or pemetrexed IV followed by carboplatin IV every 21 days during radiotherapy or etoposide IV on days 1 to 5 and days 29 to 33 followed by cisplatin IV on days 1, 8, 29, and 36 or pemetrexed IV followed by cisplatin IV every 21 days during radiotherapy. Patients then receive consolidation durvalumab IV every 2 or 4 weeks for up to one year or osimertinib PO QD in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and/or PET/CT during follow-up.

Interventions

CarboplatinDRUG

Given IV

Also known as: Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carboplatinum, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, JM8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo