Clinical trial NCT05451173: Combining ICI With SBRT or HypoFrx-RT for ES NSCLC
Official title: 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.
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Non-small Cell Lung Cancer
Non-small Cell Carcinoma
Non-small Cell Lung Cancer Stage I
Non-small Cell Lung Cancer Stage II
Non-small Cell Lung Cancer Stage III
Keywords: NSCLC, Stereotactic body radiotherapy, SBRT, Hypofractionated, Radiotherapy
Lead sponsor: Xuanwu Hospital, Beijing
Sponsor class: OTHER
First posted: 2022-07-11
Enrollment: 83
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel assignment
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Maximum tolerated dose (MTD)
timeFrame: 2 years
measure: The incidence of any adverse events that is >= grade 3
timeFrame: 2 years
measure: Progression-free survival (PFS)
timeFrame: 2 years
Secondary outcomes:
measure: Local control
timeFrame: 2 years
measure: Overall survival (OS)
timeFrame: 2 years
measure: Quality of Life (QoL)
timeFrame: 2 years
measure: Quality of Life (QoL), Lung cancer specific
timeFrame: 2 years
Other outcomes:
Locations:
city: Beijing
country: China
facility: Capital Medical University Xuanwu Hospital
state: Beijing
Study officials:
affiliation: Capital Medical University
name: Alexander Chi, MD
role: STUDY_CHAIR
References: