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

Official title

(PRESTO) A Randomized Phase II Trial Evaluating Hotspots in Stereotactic Ablative Radiotherapy for Early-Stage Non-Small Cell Lung Cancer

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.

Detailed description

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

• Procedure Biospecimen Collection
  Undergo blood sample collection
• Procedure Computed Tomography
  Undergo CT scan
• Procedure Lymph Node Biopsy
  Undergo lymph node sampling
• Procedure Positron Emission Tomography
  Undergo PET scan
• Radiation Stereotactic Body Radiation Therapy
  Receive SOC SBRT
• Radiation Stereotactic Body Radiation Therapy
  Receive hot spot SBRT
• Other Survey Administration
  Ancillary studies

Primary outcome measures

• Time to progression (local control) [Time frame: Up to 2 years]

Secondary outcome measures (7)

• Progression free survival (PFS) [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) [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 [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 [Time frame: Up to 3 years]
• Change in Quality of life [Time frame: Up to 3 years]
• Incidence of grade 3+ adverse events [Time frame: Up to 3 years]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• Roswell Park Cancer Institute — Buffalo

Identifiers

NCT: NCT07718672 · I-4050824 · NCI-2026-04889 · I-4050824

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗