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Immunotherapy SBRT Sensitization of the Programmed Death-1 (PD-1) Effect (I-SABR)

Primary Purpose

Metastatic Nonsmall Cell Lung Cancer, Non Small Cell Lung Cancer

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Stereotactic Body Radiotherapy

About this trial

This is an interventional treatment trial for Metastatic Nonsmall Cell Lung Cancer focused on measuring Opdivo, Keytruda, Cyberknife

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Histologically or cytologically confirmed Stage IV NSCLC according to the 7th AJCC staging manual.
Eligible for an immunotherapy agent. Patients who progress after drug therapy (3 months) for ALK, EGFR or ROS mutation positive lung cancer are eligible.
At least 2 lesions that are safely amenable to SBRT. ECOG <=2.
At least 1 measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria for response assessment or at least 1 lesion with FDG avidity and CT correlate that can be monitored for PET-CT response by SUV Max increase or decrease.
Normal Hepatic and renal function.
Bone marrow reserve:
1. ANC ≥ 1.5 x 109/L
2. Hemoglobin ≥9.0 g/dL
3. Platelet count ≥75 x 109/L
Ability to comply with follow-up visits and evaluations, treatment planning and studies and other study related procedures and visits.
Ability to sign informed consent.

Exclusion Criteria:

Patients with active CNS metastases
Active, known or suspected auto-immune disease.
Patients with medical conditions that require systemic immunosuppression.
Patients with a history of interstitial lung disease.
Prior treatment with immune checkpoint inhibitors/immonotherapy.
Other active malignancy requiring intervention.
Prior lung radiation, with the only metastatic targets in the lungs.
Unresolved toxicity from prior chemotherapy or anti-cancer treatment.
Current or prior enrollment in clinical trial with an investigational drug within 4 weeks.
Pregnancy or positive pregnancy test.

Sites / Locations

Philadelphia CyberKnife

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment Arm

Arm Description

Outcomes

Primary Outcome Measures

Overall Survival

Determine overall survival in patients receiving SBRT and immunotherapy as compared to landmark trials of patients receiving immunotherapy alone (Checkmate 057, Keynote 024)

Acute Toxicity: Radiation pnuemonitis measured using NCI CTCAE version 4.0

Determine excess/unexpected toxicity that cannot be attributed to routine radiation therapy or immunotherapy side effects.

Secondary Outcome Measures

Progression Free Survival

1. To determine the progression free survival measured from time of enrollment to first evidence of progressive disease and evaluated 3 months after treatment initiation

Local Control

To determine the local control measured from time of enrollment to first evidence of progressive disease at the treatment site

Late Toxicity: Pulmonary, Bone or Visceral organ toxicity evaluated 6 months from completion of treatment using NCI CTCAE version 4.

the incidence of grade ≥ 3 , pneumonitis 6 months after completing SBRT the incidence of any grade pulmonary fibrosis 6 months after completing SBRT the incidence of grade ≥ 3 , bone fracture 6 months after completing SBRT the incidence of grade ≥ 3 visceral organ toxicity at or near a treated site (e.g colitis, nephritis, hepatitis) 6 months after completing SBRT

Impact of Tumor Burden

To determine the influence of number of metastatic sites on OS, and PFS. Patients will be stratified based on number of metastatic sites <=3, 4-5, >5

Full Information

NCT ID

NCT03825510

First Posted

August 18, 2017

Last Updated

March 3, 2023

Sponsor

Crozer-Keystone Health System

Collaborators

Saint Peters University Hospital, Community Medical Center, Toms River, NJ

1. Study Identification

Unique Protocol Identification Number

NCT03825510

Brief Title

Immunotherapy SBRT Sensitization of the Programmed Death-1 (PD-1) Effect

Acronym

I-SABR

Official Title

A Prospective Trail of Immunotherapy and Stereotactic Body Radiotherapy (SBRT) for the Treatment of Metastatic Lung Cancer: SBRT Sensitization of the Programmed Death-1 (PD-1) Effect

Study Type

Interventional

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Completed

Study Start Date

April 28, 2017 (Actual)

Primary Completion Date

March 8, 2022 (Actual)

Study Completion Date

March 8, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Crozer-Keystone Health System

Collaborators

Saint Peters University Hospital, Community Medical Center, Toms River, NJ

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Yes

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The purpose of this study is to determine efficacy, safety of Stereotactic Body Radiotherapy (SBRT) in combination with immunotherapy in participants with metastatic non-small cell lung cancer (NSCLC) who are eligible for an immunotherapy agent.

Detailed Description

Blockade of the PD-1/PD-L1 T-cell checkpoint pathway is an effective and well tolerated approach to stimulating the immune response which is a critical option in the treatment of metastatic NSCLC. However, progression free survival (PFS) is increased by only 2-4 months and median overall survival (OS) by 3-9 months. There is compelling evidence that PFS is increased up to 3 fold and OS by 2 fold in patients receiving a course of radiation therapy while on immunotherapy. Radiotherapy is known to induce immunogenic tumor cell death and upregulation of dendritic cells and antigen presentation leading to activation of cytotoxic T-Cells. Dramatic T-cell activation has been demonstrated where tumor regression occurs outside the radiation treatment field in a phenomenon termed the abscopal effect and is associated with high dose radiation delivered via SBRT. As such, SBRT activation of T-cells could be complementary to immunotherapy and enhance T-cell mediated killing via PD-L1 blockade which could lead to lasting and durable tumor response with improved progression free survival and overall survival.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Metastatic Nonsmall Cell Lung Cancer, Non Small Cell Lung Cancer

Keywords

Opdivo, Keytruda, Cyberknife

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

3 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Treatment Arm

Arm Type

Experimental

Intervention Type

Radiation

Intervention Name(s)

Stereotactic Body Radiotherapy

Other Intervention Name(s)

SBRT, SRS, SABR, CyberKnife

Intervention Description

All patients in this trial will be treated with fractionated Stereotactic body radiation therapy. SBRT will be delivered to <=3 sites in 3-5 fractions followed by administration of the specified immunotherapy agent (Nivolumab or Pembrolizumab). This approach will take advantage of the transient increase in antigen availability, increased antigen presentation and upregulation of PD-1 by tumor cells following ablative radiation therapy.

Primary Outcome Measure Information:

Title

Overall Survival

Description

Determine overall survival in patients receiving SBRT and immunotherapy as compared to landmark trials of patients receiving immunotherapy alone (Checkmate 057, Keynote 024)

Time Frame

24 months

Title

Acute Toxicity: Radiation pnuemonitis measured using NCI CTCAE version 4.0

Description

Determine excess/unexpected toxicity that cannot be attributed to routine radiation therapy or immunotherapy side effects.

Time Frame

0-15 weeks

Secondary Outcome Measure Information:

Title

Progression Free Survival

Description

1. To determine the progression free survival measured from time of enrollment to first evidence of progressive disease and evaluated 3 months after treatment initiation

Time Frame

3-24 Months

Title

Local Control

Description

To determine the local control measured from time of enrollment to first evidence of progressive disease at the treatment site

Time Frame

0-24 Months

Title

Late Toxicity: Pulmonary, Bone or Visceral organ toxicity evaluated 6 months from completion of treatment using NCI CTCAE version 4.

Description

Time Frame

6-24 Months

Title

Impact of Tumor Burden

Description

To determine the influence of number of metastatic sites on OS, and PFS. Patients will be stratified based on number of metastatic sites <=3, 4-5, >5

Time Frame

24 Months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Histologically or cytologically confirmed Stage IV NSCLC according to the 7th AJCC staging manual. Eligible for an immunotherapy agent. Patients who progress after drug therapy (3 months) for ALK, EGFR or ROS mutation positive lung cancer are eligible. At least 2 lesions that are safely amenable to SBRT. ECOG <=2. At least 1 measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria for response assessment or at least 1 lesion with FDG avidity and CT correlate that can be monitored for PET-CT response by SUV Max increase or decrease. Normal Hepatic and renal function. Bone marrow reserve: ANC ≥ 1.5 x 109/L Hemoglobin ≥9.0 g/dL Platelet count ≥75 x 109/L Ability to comply with follow-up visits and evaluations, treatment planning and studies and other study related procedures and visits. Ability to sign informed consent. Exclusion Criteria: Patients with active CNS metastases Active, known or suspected auto-immune disease. Patients with medical conditions that require systemic immunosuppression. Patients with a history of interstitial lung disease. Prior treatment with immune checkpoint inhibitors/immonotherapy. Other active malignancy requiring intervention. Prior lung radiation, with the only metastatic targets in the lungs. Unresolved toxicity from prior chemotherapy or anti-cancer treatment. Current or prior enrollment in clinical trial with an investigational drug within 4 weeks. Pregnancy or positive pregnancy test.

Facility Information:

Facility Name

Philadelphia CyberKnife

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19083

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Immunotherapy SBRT Sensitization of the Programmed Death-1 (PD-1) Effect

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