Comparing Hypo-fractionated Intensity- Modulated Radiation Therapy to Standard- Fractionated IMRT Along With Chemotherapy and Immunotherapy for Non-Small Cell Lung Cancer

A Randomized Phase II Trial of Hypo-fractionated Intensity-Modulated Radiation Therapy (IMRT) Utilizing 2.5 Gy/Fraction Versus (VS) Standard-Fractionated IMRT, Concurrent With Carboplatin/Paclitaxel and Followed by Consolidation Durvalumab, for Subjects With Stage 2A/B Non-Small Cell Lung Cancer

The hypothesis for this study is that hypofractionated IMRT to 62.5 Gy in 25 fractions (2.5 Gy/fraction) with concurrent carboplatin and paclitaxel, followed by maintenance durvalumab will improve locoregional control at 18 months by 10% compared to standard-fractionated chemo-IMRT/durvalumab. A modest improvement in locoregional control (LRC) was selected as a target which could merit further study of this hypofractionated IMRT regimen in a Phase III trial

Study Overview

• Status: Recruiting
• Conditions: Non Small Cell Lung Cancer Stage
• Intervention / Treatment: Radiation: Hypo-Fractionation; Radiation: Standard-Fractionation

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: KUCC Navigation; Phone Number: 913-588-3671; Email: kucc_navigation@kumc.edu

Study Locations

• United States
  • Kansas
    • Kansas City, Kansas, United States, 66205
      • Recruiting
      • The University of Kansas Cancer Center, Westwood Campus
      • Contact: KUCC Navigation; Phone Number: 913-588-3671; Email: kucc_navigation@kumc.edu
    • Overland Park, Kansas, United States, 66210
      • Recruiting
      • The University of Kansas Cancer Center, Overland Park Clinic
      • Contact: Clinical Trials Nurse Navigator; Phone Number: 913-945-7552; Email: ctnursenav@kumc.edu
    • Topeka, Kansas, United States, 66606
      • Not yet recruiting
      • KUCC MCA- TUKHS, Saint Francis Hospital
      • Contact: KUCC Navigation; Phone Number: 913-588-3671; Email: kucc_navigation@kumc.edu
  • Missouri
    • Kansas City, Missouri, United States, 64154
      • Recruiting
      • The University of Kansas Cancer Center, North Clinic
      • Contact: Clinical Trials Nurse Navigator; Phone Number: 913-945-7552; Email: ctnursenav@kumc.edu
    • Lee's Summit, Missouri, United States, 64064
      • Recruiting
      • The University of Kansas Cancer Center, Lee's Summit Clinic
      • Contact: Clinical Trials Nurse Navigator; Phone Number: 913-945-7552; Email: ctnursenav@kumc.edu
    • North Kansas City, Missouri, United States, 64116
      • Recruiting
      • University of Kansas Cancer Center, North Kansas City Hospital
      • Contact: Nurse Navigator; Phone Number: 913-945-7552; Email: CTNurseNav@kumc.edu

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Ability of participant OR Legally Authorized Representative (LAR) to understand this study, and participant or LAR willingness to sign a written informed consent
• Males and females age ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0 - 2
• Measurable disease by RECIST 1.1
• Women of childbearing potential must have a negative serum pregnancy test within one month prior to initiating treatment
• Pathologically proven diagnosis of Stage IIIA or IIIB non-small cell lung cancer (NSCLC)
• No Positron Emission Tomography (PET)/CT evidence of metastatic disease
• An MRI of the brain with contrast excluding intracranial metastatic disease (or CT with contrast if MRI is medically contraindicated). An MRI without contrast is only permitted if the subject cannot have contrast for medical reasons
• If a pleural effusion is present, it must be tapped and confirmed to be cytologically negative. If an effusion is deemed too small to safely tap, the subject will be eligible
• Women of child-bearing potential and men with partners of child-bearing potential must agree to practice sexual abstinence or to use the forms of contraception listed in Child-Bearing Potential/Pregnancy section for the duration of study participation and for 90 days following completion of therapy
• Adequate organ function per laboratory results

Exclusion Criteria:

• Current or anticipating use of other anti-neoplastic or investigational agents while participating in this study
• Diagnosed with a psychiatric illness or is in a social situation that would limit compliance with study requirements
• Evidence of severe or systemic disease (e.g., unstable or uncompensated respiratory, cardiac, hepatic, or renal disease) that would interfere with study protocol as judged by the investigator
• Is pregnant or breastfeeding
• Active connective tissue disorders, such as active lupus or scleroderma
• Known Acquired Immune Deficiency (HIV (+)/AIDS)
• Has a known allergic reaction to any excipient contained in the study drug formulations
• Active Grade 3 (per the NCI CTCAE, Version 5.0) or higher viral, bacterial, or fungal infection within 2 weeks prior to the first dose of study treatment
• Prior thoracic radiotherapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hypo-Fractionation; Participants will receive one fraction of radiation therapy a day for 5 days each week for 5 weeks along with weekly chemotherapy with Paclitaxel 45 milligram per meter squared (mg/m2) through intravenous (IV)infusion for 1 hour followed by Carboplatin area under the curve (AUC) 2 IV for 30 minutes for approximately 5 or 6 weeks. Once complete, participant will receive Durvalumab, 1500 mg, IV every 4 weeks for 12 months.	Radiation: Hypo-Fractionation; 62.5 Gy in 25 fractions of 2.5 Gy/fraction
Active Comparator: Standard-Fractionation; Participants will receive one fraction of radiation therapy a day for 5 days each week for 6 weeks along with weekly chemotherapy with Paclitaxel 45 milligram per meter squared (mg/m2) through intravenous (IV)infusion for 1 hour followed by Carboplatin AUC 2 IV for 30 minutes for approximately 5 or 6 weeks. Once complete, participant will receive Durvalumab, 1500 mg, IV every 4 weeks for 12 months.	Radiation: Standard-Fractionation; 60 Gy in 30 fractions of 2 Gy/fraction

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Locoregional control (LRC)	RECIST 1.1	From enrollment for up to 7.5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute toxicities	CTCAE v. 5.0	From enrollment for up to 7.5 years
Late toxicities	CTCAE v. 5.0	From enrollment for up to 7.5 years
Progression free survival (PFS)	RECIST 1.1	From enrollment for up to 7.5 years
Overall survival (OS)	Kaplan-Meier	From enrollment for up to 7.5 years
Measuring the Impact of Treatment on the Quality of life (QOL)	EORTC Quality of Life Questionnaire (QLQ)-C30	From enrollment for up to 7.5 years
Measuring the Impact of Treatment on the Quality of life (QOL)	QLQ-Lung Cancer (LC)29	From enrollment for up to 7.5 years

Collaborators and Investigators

• Sponsor: University of Kansas Medical Center
• Investigators: Principal Investigator: Krishna Reddy, MD, PhD, University of Kansas Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): February 25, 2022
• Primary Completion (Estimated): October 1, 2025
• Study Completion (Estimated): November 1, 2026

Study Registration Dates

• First Submitted: July 28, 2021
• First Submitted That Met QC Criteria: July 28, 2021
• First Posted (Actual): August 5, 2021

Study Record Updates

• Last Update Posted (Actual): December 7, 2023
• Last Update Submitted That Met QC Criteria: December 5, 2023
• Last Verified: December 1, 2023

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: IIT-2021-LU-HypoIMRT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes