Combining ICI With SBRT or HypoFrx-RT for ES NSCLC

Combining an Immune Checkpoint Inhibitor With SBRT or Hypo-fractionated RT in the Treatment of Stage I-III NSCLC: an Exploratory Study on Radiation Dose and Treatment Efficacy.

This study will explore the best dose of radiation to be used when treating stage I-III non-small cell lung cancer (NSCLC) with stereotactic body radiation therapy (SBRT) or hypo-fractionated radiotherapy (HypoFrx-RT) that is delivered in combination with an immune checkpoint inhibitor. Treatments with SBRT or HypoFrx-RT for locally confined NSCLC show positive response which may be further augmented when they are combined with an immune checkpoint inhibitor. Currently, it is not understood what radiation dose is most suitable for such combined treatments and their clinical efficacy in the treatment of early stage (ES) NSCLC. Therefore, this study can help researchers gain insight into what a safe and effective SBRT or HypoFrx-RT dose will be when such radiotherapeutic approaches are combined with concurrent and adjuvant administration of an immune checkpoint inhibitor in the treatment of ES NSCLC.

Study Overview

• Status: Not yet recruiting
• Conditions: Non-small Cell Lung Cancer Stage III; Non-small Cell Lung Cancer; Non-small Cell Lung Cancer Stage I; Non-small Cell Carcinoma; Non-small Cell Lung Cancer Stage II
• Intervention / Treatment: Radiation: Stereotactic body radiotherapy; Radiation: Hypofractionated radiotherapy; Drug: Durvalumab

Detailed Description

Patients will be assigned to Cohort A or Cohort B based on tumor stage (AJCC 8th Ed.).

Cohort A: cT1-T3, N0, M0 (selected cT1, No, M0)

Cohort B: cT4, N0, M0; cT1-4, N1-3, M0

Phase I:

This portion of the study will utilize a standard 3 + 3 phase I design with three patients enrolled per radiation dose level in each cohort. Enrollment in the two cohorts is independent from one another. In both cohorts, an anti-PD-(L)1 immune checkpoint inhibitor will be given concurrently and adjuvantly with radiotherapy for approximately 1 year.

The radiation dose escalation for each cohort is listed below:

Cohort A (SBRT):

(Optional): 8 Gy x 5 daily fractions

Level 1: 9 Gy x 5 daily fractions

Level 2: 10 Gy x 5 daily fractions

Level 3: 11 Gy x 5 daily fractions

Cohort B (HypoFrx-RT):

(Optional): 3 Gy x 15 daily fractions

Level 1: 3.5 Gy x 15 daily fractions

Level 2: 4 Gy x 15 daily fractions

DLTs will be based on events occurring during the course of radiotherapy.

Concurrent administration of an immune checkpoint inhibitor is defined as:

An anti-PD-(L)1 immune checkpoint inhibitor administered with standard dosing (Durvalumab: 1500 mg every 4 weeks) given within 5 days prior to the beginning of radiotherapy.

Adjuvant administration of an immune checkpoint inhibitor is defined as:

An anti-PD-(L)1 immune checkpoint inhibitor administered with standard dosing (Durvalumab: 1500 mg every 4 weeks) for approximately 1 year or until progression or other discontinuation criteria are met.

Phase II:

Once a maximum tolerated dose (MTD) is defined in each cohort, this dose will be used as the only radiation dose in each corresponding cohort in the phase II portion of this study. Dosing regimen of the immune checkpoint inhibitor will remain the same as that used in the phase I portion of this study.

For this protocol, patients will be followed up to 2 years after the last dose of immune checkpoint inhibitor is administered.

• Study Type: Interventional
• Enrollment (Estimated): 83
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Alexander Chi, MD; Phone Number: 5718391855; Email: achiaz2010@gmail.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100053
      • Capital Medical University Xuanwu Hospital
      • Contact: Alexander Chi; Phone Number: 18701866689

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

Key Inclusion Criteria

1. Informed Consent
2. Stage I-III NSCLC per AJCC 8th. ed.
3. Tumor PD-L1 expression ≥1% preferred
4. Tumor sample submission
5. Tumor staging prior to registration
6. Age ≥ 18 years
7. WHO/ECOG PS of 0, 1, or 2
8. Life expectancy ≥12 weeks
9. Adequate organ or bone marrow function
10. Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients.

Exclusion Criteria:

Key Exclusion Criteria

1. Mixed small cell and non-small cell lung cancer histology
2. Definitive clinical or radiologic evidence of metastatic disease
3. Patients who received systemic therapy for the current cancer prior to enrollment
4. Thoracic radiotherapy within 5 years with exceptions
5. Major surgery within 28 days prior to enrollment with exception
6. Prior exposure to any anti-PD-1 or anti-PD-L1 antibody
7. History of another primary malignancy with exceptions
8. History of idiopathic pulmonary fibrosis, any pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on chest PET/CT or CT scan
9. Active or prior documented autoimmune disease with exceptions
10. History of primary immunodeficiency
11. History of allogenic organ or tissue transplantation

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A; SBRT to be delivered with concurrent and adjuvant anti-PD-(L)1 immune checkpoint inhibitor.	Radiation: Stereotactic body radiotherapy; An ablative dose of radiation is delivered to the primary tumor target over 1-2 week.; Other Names: SBRT; Drug: Durvalumab; an anti-PD-(L)1 immune checkpoint inhibitor is administered concurrently and adjuvantly with radiotherapy.
Experimental: Cohort B; Hypo-fractionated radiotherapy to be delivered with concurrent and adjuvant anti-PD-(L)1 immune checkpoint inhibitor.	Radiation: Hypofractionated radiotherapy; Hypofractionated radiotherapy is delivered to the primary tumor and any involved lymph node target(s) over 3 weeks.; Other Names: HypoFrx-RT; Drug: Durvalumab; an anti-PD-(L)1 immune checkpoint inhibitor is administered concurrently and adjuvantly with radiotherapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum tolerated dose (MTD)	MTD in cohort A and cohort B, respectively.	2 years
The incidence of any adverse events that is >= grade 3	Adverse events will be graded according to CTCAE v.5.0	2 years
Progression-free survival (PFS)	PFS is defined as free from any disease progression or death after combined treatment for NSCLC.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Local control	To report the local control rate along with the rate of regional control and distant metastasis after combined treatment for NSCLC.	2 years
Overall survival (OS)	To report OS after combined treatment	2 years
Quality of Life (QoL)	To determine the QoL pertaining to any cancer patients before and after treatment using the European Organisation of Research and Treatment of Cancer Quality of Life Questionnaire, Core 30 (EORTC QLQ-C30) scales.	2 years
Quality of Life (QoL), Lung cancer specific	To determine the QoL before and after treatment using the European Organisation of Research and Treatment of Cancer Quality of Life Questionnaire that is specific to lung cancer patients, the Lung Cancer 29(LC 29) scoring scales.	2 years

Collaborators and Investigators

• Sponsor: Alexander Chi
• Investigators: Study Chair: Alexander Chi, MD, Capital Medical University

Study record dates

Study Major Dates

• Study Start (Estimated): October 9, 2023
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: June 29, 2022
• First Submitted That Met QC Criteria: July 5, 2022
• First Posted (Actual): July 11, 2022

Study Record Updates

• Last Update Posted (Actual): October 3, 2023
• Last Update Submitted That Met QC Criteria: September 30, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: NSCLC, Stereotactic body radiotherapy, SBRT, Hypofractionated, Radiotherapy
• 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; Antineoplastic Agents; Antineoplastic Agents, Immunological; Durvalumab
• Other Study ID Numbers: SF 2022-2-1042

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