Combining ICI With SBRT or HypoFrx-RT for ES NSCLC

Sponsor

Alexander Chi (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05451173

Collaborator

(none)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
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	Radiation: Stereotactic body radiotherapy Radiation: Hypofractionated radiotherapy Drug: Durvalumab	Phase 1/Phase 2

Detailed Description

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

Cohort A: cT2a-T3, N0, M0 (limited cT1c, 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 Design

Study Type:

Interventional

Anticipated Enrollment :

83 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Parallel assignmentParallel assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Aug 1, 2022

Anticipated Primary Completion Date :

Dec 31, 2024

Anticipated Study Completion Date :

Dec 31, 2024

Arms and Interventions

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-L1 immune checkpoint inhibitor is administered concurrently and adjuvantly with radiotherapy. Other Names: Imfinzi
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-L1 immune checkpoint inhibitor is administered concurrently and adjuvantly with radiotherapy. Other Names: Imfinzi

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-L1 immune checkpoint inhibitor is administered concurrently and adjuvantly with radiotherapy.

Other Names:

Imfinzi

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-L1 immune checkpoint inhibitor is administered concurrently and adjuvantly with radiotherapy.

Other Names:

Imfinzi

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

Local control [2 years]
To report the local control rate along with the rate of regional control and distant metastasis after combined treatment for NSCLC.
Overall survival (OS) [2 years]
To report OS after combined treatment
Quality of Life (QoL) [2 years]
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.
Quality of Life (QoL), Lung cancer specific [2 years]
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.
Descriptive statistics of biomarkers [2 years]
Biomarkers will be analyzed from blood and tissue specimens obtained before, during, and after combined treatments

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Key Inclusion Criteria

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

Exclusion Criteria:

Key Exclusion Criteria

Mixed small cell and non-small cell lung cancer histology
Definitive clinical or radiologic evidence of metastatic disease
Patients who received systemic therapy for the current cancer prior to enrollment
Thoracic radiotherapy within 5 years with exceptions
Major surgery within 28 days prior to enrollment with exception
Prior exposure to any anti-PD-1 or anti-PD-L1 antibody
History of another primary malignancy with exceptions
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
Active or prior documented autoimmune disease with exceptions
History of primary immunodeficiency
History of allogenic organ or tissue transplantation

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

Alexander Chi

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Alexander Chi, Professor, Beijing Chest Hospital

ClinicalTrials.gov Identifier:

NCT05451173

Other Study ID Numbers:

SF 2022-2-1042

First Posted:

Jul 11, 2022

Last Update Posted:

Jul 11, 2022

Last Verified:

Jul 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Yes

Keywords provided by Alexander Chi, Professor, Beijing Chest Hospital

NSCLC, Stereotactic body radiotherapy, SBRT, Hypofractionated, Radiotherapy

Additional relevant MeSH terms:

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Durvalumab

Study Results

No Results Posted as of Jul 11, 2022