Combining ICI With SBRT or HypoFrx-RT for ES NSCLC

Non-small Cell Lung Cancer Clinical Trial

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.

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05451173
• Other study ID #: SF 2022-2-1042
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• Start date: October 9, 2023
• Est. completion date: December 31, 2025

Study information

• Verified date: September 2023
• Source: Xuanwu Hospital, Beijing
• Contact: Alexander Chi, MD
• Phone: 5718391855
• Email: achiaz2010[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 83
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-small Cell Carcinoma
• Non-small Cell Lung Cancer
• Non-small Cell Lung Cancer Stage I
• Non-small Cell Lung Cancer Stage II
• Non-small Cell Lung Cancer Stage III

Intervention

Radiation:
• Stereotactic body radiotherapy
An ablative dose of radiation is delivered to the primary tumor target over 1-2 week.
• Hypofractionated radiotherapy
Hypofractionated radiotherapy is delivered to the primary tumor and any involved lymph node target(s) over 3 weeks.

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

Locations

Country	Name	City	State
China	Capital Medical University Xuanwu Hospital	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Alexander Chi

Country where clinical trial is conducted

China, 

Outcome

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