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

NCT ID: NCT03825510

Last Updated: 2023-03-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-04-28
• Study Completion Date: 2022-03-08

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.

Conditions

Metastatic Nonsmall Cell Lung Cancer; Non Small Cell Lung Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment Arm

Group Type: EXPERIMENTAL

Stereotactic Body Radiotherapy

Intervention Type: RADIATION

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.

Interventions

Stereotactic Body Radiotherapy

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.

Intervention Type: RADIATION

Other Intervention Names

SBRT; SRS; SABR; CyberKnife

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:

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Saint Peters University Hospital

OTHER

Sponsor Role: collaborator

Community Medical Center, Toms River, NJ

OTHER

Sponsor Role: collaborator

Crozer-Keystone Health System

OTHER

Sponsor Role: lead

Responsible Party

Rachelle Lanciano M.D.

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Philadelphia CyberKnife

Philadelphia, Pennsylvania, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Other Identifiers

CKHS 17-009

Identifier Type: -

Identifier Source: org_study_id