Study of Hypofractionated Radiotherapy Alone in Locally Advanced Nonsmall Cell Lung Cancer Patients

A Single Arm Phase II Study of Hypofractionated Radiotherapy Alone in Locally Advanced Nonsmall Cell Lung Cancer Patients Who Decline or Are Ineligible for Surgery or Chemotherapy

The purpose of this research study is to find out what effects (good or bad) may come from a new way of doing radiation therapy for lung cancer. This study is for patients who are not able to get surgery or chemotherapy with their radiation. The way of doing radiation therapy in this trial is called hypofractionated radiation therapy which is a standard approach, but this study allows the actual tumor to get an extra radiation dose while still protecting the organs that are near the tumor.

Study Overview

• Status: Terminated
• Conditions: Nonsmall Cell Lung Cancer Stage III; Nonsmall Cell Lung Cancer, Stage II
• Intervention / Treatment: Drug: Hypofractionated Radiation Therapy; Radiation: Radiation Boost

Detailed Description

Primary Objective:

• To determine the in-field control of hypofractionated radiotherapy consisting of 70 Gy in 25 fractions without concurrent chemotherapy measured at two years after the first post- radiotherapy scan.

Secondary Objective(s):

• To determine the toxicity profile of thoracic hypofractionated radiotherapy consisting of 70 Gy in 25 fractions as graded by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
• To determine proportion with local, regional, and distant progression at 1 and 2 years after the first post-radiotherapy scan, and compute progression-free and overall survival (progression-free survival and overall survival, respectively).

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histological confirmation of non-small cell lung cancer by either biopsy or cytology
• American Joint Committee on Cancer (AJCC) 8th Edition Stage II-III or ultracentral Stage IB disease as determined by PET/CT and MRI Brain
• Ultracentral disease will be defined as edge of gross visible tumor within 1.0 cm of the proximal bronchial tree.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-3
• Participant is not eligible for or has declined surgical resection or stereotactic body radiotherapy as determined by the treating physician
• Participant is not eligible for or has declined concurrent chemotherapy as determined by the treating physician
• While investigators expect it to be an uncommon event, sequential use of systemic therapy after completion of radiation therapy is permissible if the participant's status improves such that they become eligible for such therapies, per the discretion of a multidisciplinary tumor board.
• Negative serum or urine pregnancy test within 2 weeks of the date of enrollment for women of child-bearing potential.
• Ability to understand and the willingness to sign an IRB-approved informed consent document (either directly or via a legally authorized representative).

Exclusion Criteria:

• History of previous thoracic radiotherapy with the exception of prior radiotherapy for breast cancer without overlap of the fields with the cancer to be treated.
• Prior systemic therapy or surgery for the study cancer.
• Prior malignancy within the past two years except for non-melanoma skin cancer, prostate cancer, or any in-situ malignancy.
• Receipt of anti-angiogenic therapy, such as bevacizumab, within 6 months of enrollment.
• Pregnant women are excluded from this study because radiation therapy has known potential for teratogenic or abortifacient effects.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Hypofractionated Radiation Therapy; Hypofractionated radiation therapy will be delivered to all participants. The radiation will be planned in a special way to give the biggest parts of the tumors that are the most difficult to control a little more radiation every day than the lower risk areas.

Drug: Hypofractionated Radiation Therapy; The prescribed dose will be 70 Gy in 25 fractions. Participants will radiation therapy once a day for 25 days, Monday through Friday (around 5 weeks).; Radiation: Radiation Boost; Undergo simultaneous integrated boost (SIB) to treat both planned target volumes with daily image guidance. This approach allows daily confirmation of target localization and simultaneous delivery of lower dose per fraction to low risk areas while maintaining a high dose per fraction to the highest risk areas.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Presence or Absence of In-Field Progression	In-field progression is defined as growth of the targeted lesions beyond the treated volume. The treated volume will be defined as the 28.75 Gy isodose line (50% of 57.5 Gy). Pathologic confirmation of tumor progression is preferred, but can be determined radiographically by Multidisciplinary Thoracic Oncology Program consensus if biopsy of the lesion in question is not feasible or safe. Investigators will compare the proportion of the sample with any in-field progression at 2 years to the historical control proportion of 0.5, using a one-sample z-test.	At 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Participants Experiencing Grade 2 or Higher Toxicities	Toxicities will be evaluated per Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 constructed with a 95% confidence interval.	25 months
Proportion of Participants That Experienced Local Progression	Participants who have experienced local progression by 13 months (1 year following first post-radiotherapy scan) and by 25 months (2 years following first post-radiotherapy scan), and will also compute the same two proportions considering regional progression, distant progression, and any (of the 3 categories) progression. A 95% confidence intervals around these proportions will be constructed. Participants for whom investigators are unable to determine progression status at 1 and 2 years (e.g., because they do not return for the necessary scans, or because they die without evidence of progression) will be left out of these analyses.	At 1 and 2 years after first post-radiotherapy scan
Progression-Free Survival	Progression-free survival will be evaluated by considering the time from registration to progression of disease or death; those who do not experience either outcome will be censored at date of last visit. Using the Kaplan-Meier lifetable method, and will estimate median survival and corresponding 95% confidence intervals; investigators will also explore simple Cox proportional hazards models of this survival outcomes, to examine the predictive influence of variables such as age, gender, ECOG performance status, stage at diagnosis, planning target volume (PTV) 7000 volume, and planning target volume (PTV) 5750 volume.	Up to 2 years
Overall Survival	Overall survival will be evaluated by considering the time from registration to death from any cause; those who do not die will be censored at date of last visit. Using the Kaplan-Meier lifetable method, and will estimate median survival and corresponding 95% confidence intervals; investigators will also explore simple Cox proportional hazards models of this survival outcomes, to examine the predictive influence of variables such as age, gender, ECOG performance status, stage at diagnosis, planning target volume (PTV) 7000 volume, and planning target volume (PTV) 5750 volume.	Up to 2 years

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start (Actual): October 16, 2020
• Primary Completion (Actual): November 20, 2020
• Study Completion (Actual): November 20, 2020

Study Registration Dates

• First Submitted: May 18, 2020
• First Submitted That Met QC Criteria: May 18, 2020
• First Posted (Actual): May 21, 2020

Study Record Updates

• Last Update Posted (Actual): October 5, 2022
• Last Update Submitted That Met QC Criteria: September 26, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• 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: IRB00065905; WFBCCC 62220 (Other Identifier: Wake Forest Baptist Comprehensive Cancer Center)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No