Hotspot Stereotactic Ablative Radiotherapy Versus Traditional Stereotactic Ablative Radiotherapy for the Treatment of Early-Stage Non-Small Cell Lung Cancer

Phase 2RecruitingNCT07718672

Roswell Park Cancer Institute200 enrolled

Overview

This clinical trial compares stereotactic ablative radiotherapy (SBRT) with hot spots to standard of care SBRT for the treatment of patients with early-stage non-small cell lung cancer. SBRT with hot spots intentionally makes sure the tumor gets a higher radiation dose during treatment. This potentially may result in better control of the tumor, but also more side effects. SBRT with or without hot spots may be more effective in treating patients with early-stage non-small cell lung cancer, compared to standard of care SBRT.

PRIMARY OBJECTIVE: I. Evaluate the impact of incorporating high isodoses termed "hot spots" in radiation therapy planning on local control. SECONDARY OBJECTIVES: I. Evaluate the impact of "hot spots" in radiation therapy planning on progression-free survival (PFS). II. Evaluate the impact of "hot spots" in radiation therapy planning on overall survival (OS). III. Evaluate the impact of tumor size on local control and if hotspot grouping impacts local control in a size-dependent manner. IV. To prospectively evaluate the PFS in early stage-non small cell lung cancer (ES-NSCLC) patients undergoing SABR who are already taking a beta-blocker as well as a potential interaction between beta-blocker usage and the perceived stress scale. V. Will evaluate for any potential interactions between quality of life (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer \[EORTC QLQ-LC13\]) and hotspot grouping. VI. Evaluate the impact of "hot spots" in radiation therapy planning on toxicity by total number of grade 3+ adverse effects. EXPLORATORY OBJECTIVE: I. Change in immune cell marker levels at week 12 post-SBRT (± 1 week) versus baseline, such as mediators of tumor antigen presentation, costimulatory molecules, immune effector cell populations, including CD4+ and CD+8 T-cells, T regulatory cells (CD4+CD25+FoxP3+), natural killer (NK) cells, monocytes, macrophages, dendritic cells (DCs) and myeloid derived suppressor cells (MDSCs). OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive standard of care (SOC) SBRT for 1-5 fractions over 1-11 days, in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT) scan with or without positron emission tomography (PET) scan and blood sample collection throughout the study. Patients may undergo lymph node sampling throughout the study. ARM II: Patients receive hot spot SBRT for 1-5 fractions over 1-11 days, in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan with or without PET scan and blood sample collection throughout the study. Patients may undergo lymph node sampling throughout the study. After completion of study treatment, patients are followed up every 3 months for 1 year and then every 3-6 months up to month 36.

Interventions

Biospecimen CollectionPROCEDURE

Undergo blood sample collection

Computed TomographyPROCEDURE

Undergo CT scan

Lymph Node BiopsyPROCEDURE

Undergo lymph node sampling

Positron Emission TomographyPROCEDURE

Undergo PET scan

Stereotactic Body Radiation TherapyRADIATION

Receive SOC SBRT

Stereotactic Body Radiation TherapyRADIATION

Receive hot spot SBRT

Survey AdministrationOTHER

Ancillary studies

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Age ≥ 18 years * Have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2 * Diagnosed with T1-3N0 biopsy-proven NSCLC of the lung. Multiple primary lung tumors are allowed; however, each lesion requires histologic confirmation * Metachronous lung tumors as defined as a new lung lesion in the setting of a historically treated lung cancer are allowed under certain conditions. The previous lung cancer must have been treated greater than 6 months prior to protocol therapy and this cancer must be considered controlled * Eligible for SABR * Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately * Participant must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure Exclusion Criteria: * Patients with a history of a prior lung cancer will be excluded only if the previous treatment is within 6 months of the protocol therapy * Mixed small cell and non-small cell lung cancer * History of allogeneic organ transplantation * History of primary immunodeficiency * Patients must not have undergone prior radiation to overlapping regions of the chest that, in the opinion of the treatment physician, will interfere with protocol treatment * Active autoimmune disease that has required systemic treatment in the last 2 years. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed * Known EGFR or ALK mutation * Past medical history of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD * Pregnant or nursing female participant * Unwilling or unable to follow protocol requirements

Outcomes

Primary Outcomes

Time to progression (local control)

Defined as no failure within the radiotherapy planning target volume (PTV), based on the international consensus on assessing local failure after stereotactic ablative radiotherapy (SBRT) will be utilized. The 2-year local control rates will be summarized by treatment arms using 90% Clopper-Pearson confidence intervals. The local control rates between arms will be compared using one-sided Cochrane-Mantel-Haenszel test (alpha=0.1), stratified by performance status, surgery candidacy, and beta-blocker usage.

Time frame: Up to 2 years

Secondary Outcomes

Progression free survival (PFS)

Will be summarized by treatment arms using the Kaplan-Meier product limit estimator.

Time frame: From the start of treatment to first documented disease progression, or death due to any cause, up to 3 years

Overall survival (OS)

Will be summarized by treatment arms using the Kaplan-Meier product limit estimator. One-sided log-rank test stratified by tumor size, performance status, and surgery candidacy will be used to compare the OS between treatment arms (alpha=0.1).

Time frame: From the start of treatment to patient death due to any cause, up to 3 years

Time to progression (local control) in a size-dependent manner

Defined as no failure within the radiotherapy PTV, based on the international consensus on assessing local failure after SBRT will be utilized.

Time frame: Up to 3 years

PFS for patients who are already taking a beta blocker

Time frame: Up to 3 years

Perception of Stress using Perceived Stress Scale

Will be measured by The Perceived Stress Scale (PSS) which assesses the perception of stress. The scale is constituted by 10 items that are self-rated by the subject on a 0-4 Likert scale. The scale minimum total score is 0, the maximum is 40. Higher total scores indicate a worse outcome

Time frame: Up to 3 years

Change in Quality of life

Assessed via European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire - Lung Cancer.

Time frame: Up to 3 years

Incidence of grade 3+ adverse events

Toxicities and adverse events (as per Common Terminology for Adverse Events version 5.0) will be summarized by the treatment arms, type, incidence, severity, seriousness, and relatedness. The rate of grade ≥ 3 AEs will be summarized as proportions with 90% Clopper Pearson confidence intervals.

Time frame: Up to 3 years

Hotspot Stereotactic Ablative Radiotherapy Versus Traditional Stereotactic Ablative Radiotherapy for the Treatment of Early-Stage Non-Small Cell Lung Cancer

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes