Testing Repeat Radiation Therapy for Recurrent Non-small Cell Lung Cancer

Phase 2Not Yet RecruitingNCT07835789

NRG Oncology138 enrolled

Overview

This phase II trial compares repeat radiation therapy (RT) to standard drug treatment alone in treating patients with stage II-III non-small cell lung cancer (NSCLC) that has come back after initial radiation at or adjacent to the site of the original tumor (locally recurrent). Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. Chemotherapy drugs used in standard drug treatment work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy drugs used in standard drug treatment may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Targeted therapy drugs used in standard treatment identify and attack specific tumor cells. This trial may help doctors determine whether repeat RT delays the cancer from growing or spreading by 6 months or more after initial radiation compared to standard drug treatment alone in patients with stage II-III locally recurrent NSCLC.

PRIMARY OBJECTIVE: I. In patients with NSCLC who develop locoregional disease recurrence after thoracic radiotherapy, to compare progression-free survival outcomes following curative-intent reirradiation versus systemic therapy alone. SECONDARY OBJECTIVES: I. To compare overall survival outcomes across study arms. II. To compare clinician-scored adverse events, scored using Common Terminology Criteria for Adverse Events (CTCAE), across study arms. III. To compare patient-reported adverse events, scored using Patient-Reported Outcomes (PRO)-CTCAE, across study arms. IV. To compare patterns of disease progression across study arms. EXPLORATORY OBJECTIVES: I. To evaluate clinical and dosimetric predictors of high-grade treatment-related toxicity within the experimental study arm. II. To compare the toxicity and efficacy of proton beam radiotherapy versus photon radiotherapy within the experimental study arm. III. To calculate regional lung ventilation using four-dimensional (4D) computed tomography (CT) planning scans and evaluate associated predictors of pulmonary toxicity. OUTLINE: Patients are randomized to 1 of 2 arms. ARM 1: Patients receive standard of care (SOC) systemic therapy, which may include chemotherapy, immunotherapy, and/or targeted therapy on study. Patients also undergo positron emission tomography/computed tomography (PET/CT) and magnetic resonance imaging (MRI) during screening, as well as chest CT and optional blood sample collection throughout the study. ARM 2: Patients undergo radiation therapy (RT) for 20 treatment fractions over approximately 5 weeks or RT for 30 treatment fractions over approximately 6 weeks in the absence of disease progression or unacceptable toxicity. Patients receiving 6-week RT may also receive chemotherapy during RT per decision of patient and doctor decision. Patients also undergo PET/CT and MRI during screening, as well as chest CT and optional blood sample collection throughout the study. After completion of study treatment, patients are followed up periodically until 5 years.

Interventions

Biospecimen CollectionPROCEDURE

Undergo blood sample collection

Computed TomographyPROCEDURE

Undergo PET/CT and/or chest CT

ImmunotherapyOTHER

Given SOC immunotherapy

Magnetic Resonance ImagingPROCEDURE

Undergo MRI

Positron Emission TomographyPROCEDURE

Undergo PET/CT

Radiation TherapyRADIATION

Undergo repeat RT

Systemic ChemotherapyDRUG

Given SOC chemotherapy

Targeted TherapyOTHER

Given SOC targeted therapy

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * History of stage II-III NSCLC treated with fractionated (≤ 4 Gy per fraction) curative-intent (total dose ≥ 45 Gy) thoracic radiotherapy, completed ≥ 12 months before study entry * Participants must have recurrent/progressive disease in the lung and/or regional lymph nodes that is not suitable for treatment with stereotactic body radiation therapy (SBRT) and for which palliative thoracic radiotherapy is not required at the time of study entry * Biopsy to confirm recurrent/progressive disease at some point after the previous course of thoracic radiotherapy and before entering this study is required * A portion of the disease that would be treated with radiotherapy on Arm 2 of this protocol must fall within the 50% isodose cloud of the radiotherapy plan * New systemic lung cancer therapy initiated within 12 weeks prior to study entry that is still ongoing is not permitted * Participants must not have definitive clinical or radiographic evidence of distant metastatic NSCLC at present or in the past * Age ≥ 18 * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2 * Not Pregnant and Not Nursing * Negative urine or serum pregnancy test (in persons of childbearing potential) within 14 days prior to registration. Childbearing potential is defined as any person who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal * Prior thoracic radiotherapy for NSCLC must have been delivered as definitive treatment, as opposed to in the preoperative or postoperative setting. One prior radiotherapy course must meet the specifications, and the radiotherapy plan from that course must be available in Digital Imaging and Communications in Medicine (DICOM) format * Patients who have received additional prior radiotherapy (i.e., more than one prior radiotherapy course) may be enrolled, provided that only one prior radiotherapy course is deemed to affect the risks associated with treatment with radiotherapy on this study. As examples, prior radiotherapy for an extrathoracic malignancy would likely not affect the risks associated with reirradiation on this study. Prior radiotherapy for breast cancer may be permissible, depending on the extent of lung irradiation. Similarly, prior SBRT for a peripheral lung tumor may be permissible * No prior SBRT for a central lung tumor, hilar lymph node, or mediastinal lymph node * Prior lobar and sublobar lung resections are allowed, but prior pneumonectomy is not allowed * Prior chemotherapy, targeted therapy, and/or immunotherapy for lung cancer is allowed * No history of CTCAE version (v.) 5.0 grade 2-4 RT pneumonitis or ongoing CTCAE v. 5.0 grade 2-4 pneumonitis from any cause * No clinically significant interstitial lung disease

Outcomes

Primary Outcomes

Progression-free survival (PFS)

The primary analysis of PFS will be conducted in the intent-to-treat population, defined as all randomized patients. The distributions of PFS will be estimated by the Kaplan-Meier method. The primary comparison between arms will use a one-sided stratified log-rank test with the randomization stratification factors. A stratified Cox proportional hazards model will be used to estimate the hazard ratio and corresponding confidence interval. An unstratified log-rank test and unstratified Cox proportional hazards model will also be provided as sensitivity analyses. No post hoc modification or collapsing of stratification categories based on observed event counts will be performed. If the stratified Cox model is not estimable because of sparse data, the unstratified Cox model will be used to summarize the treatment hazard ratio and confidence interval, with the reason documented.

Time frame: From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first, assessed up to 5 years

Secondary Outcomes

Overall survival

Will be summarized using Kaplan-Meier methods. Comparisons between arms will be summarized descriptively using hazard ratio estimates and corresponding confidence intervals.

Time frame: From randomization to death from any cause, assessed up to 5 years

Incidence of clinician-scored treatment-related adverse events

Clinician-scored adverse events will be summarized by study arm using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE). For each patient, the maximum severity reported for each adverse event will be used in the summaries. Adverse events will be summarized regardless of relationship to protocol treatment as assessed by the investigator. All adverse events, adverse events leading to withdrawal, interruption or modification of protocol treatment, Grade ≥ 3 adverse events, and serious adverse events will be summarized. Deaths and cause of death will be summarized. Event summaries will be presented by type, grade, and attribution and will be performed at the time of the primary endpoint analysis.

Time frame: Up to 5 years

Incidence of patient-reported adverse events

A composite grading algorithm (Basch 2021) will be utilized to derive a single numerical grade for each adverse event scored at each timepoint using Patient-Reported Outcomes (PRO)-CTCAE. Patient-reported adverse events measured using PRO-CTCAE will also be summarized descriptively by arm and time point, together with compliance and missing-data patterns.

Time frame: Up to 5 years

Site of first disease progression

Patterns of first failure will be summarized descriptively by arm using the categories specified in the protocol, including locoregional/intrathoracic progression, distant progression, or both. Formal hypothesis testing for these secondary endpoints is not planned unless otherwise specified in a future statistical analysis plan.

Time frame: Up to 5 years

Testing Repeat Radiation Therapy for Recurrent Non-small Cell Lung Cancer

Overview

Conditions

Interventions

Eligibility

Outcomes

Primary Outcomes

Secondary Outcomes