Combining ICI With SBRT or HypoFrx-RT for ES NSCLC

NCT ID: NCT05451173

Last Updated: 2023-10-03

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 83 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-10-09
• Study Completion Date: 2025-12-31

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.

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort A

SBRT to be delivered with concurrent and adjuvant anti-PD-(L)1 immune checkpoint inhibitor.

Group Type: EXPERIMENTAL

Stereotactic body radiotherapy

Intervention Type: RADIATION

An ablative dose of radiation is delivered to the primary tumor target over 1-2 week.

Durvalumab

Intervention Type: DRUG

an anti-PD-(L)1 immune checkpoint inhibitor is administered concurrently and adjuvantly with radiotherapy.

Cohort B

Hypo-fractionated radiotherapy to be delivered with concurrent and adjuvant anti-PD-(L)1 immune checkpoint inhibitor.

Group Type: EXPERIMENTAL

Hypofractionated radiotherapy

Intervention Type: RADIATION

Hypofractionated radiotherapy is delivered to the primary tumor and any involved lymph node target(s) over 3 weeks.

Durvalumab

Intervention Type: DRUG

an anti-PD-(L)1 immune checkpoint inhibitor is administered concurrently and adjuvantly with radiotherapy.

Interventions

Stereotactic body radiotherapy

An ablative dose of radiation is delivered to the primary tumor target over 1-2 week.

Intervention Type: RADIATION

Hypofractionated radiotherapy

Hypofractionated radiotherapy is delivered to the primary tumor and any involved lymph node target(s) over 3 weeks.

Intervention Type: RADIATION

Durvalumab

an anti-PD-(L)1 immune checkpoint inhibitor is administered concurrently and adjuvantly with radiotherapy.

Intervention Type: DRUG

Other Intervention Names

SBRT; HypoFrx-RT

Eligibility Criteria

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

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Alexander Chi

OTHER

Sponsor Role: lead

Responsible Party

Alexander Chi

Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Alexander Chi, MD

Role: STUDY_CHAIR

Capital Medical University

Locations

Capital Medical University Xuanwu Hospital

Beijing, Beijing Municipality, China

Countries

China

Central Contacts

Alexander Chi, MD

Role: CONTACT

achiaz2010@gmail.com

5718391855

Facility Contacts

Alexander Chi

Role: primary

18701866689

Other Identifiers

SF 2022-2-1042

Identifier Type: -

Identifier Source: org_study_id