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

NCT03825510 | Completed Phase 2 DMC FDA Device

• 1 other identifier: CKHS 17-009
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

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.

Conditions

Metastatic Nonsmall Cell Lung Cancer; Non Small Cell Lung Cancer

Keywords

Opdivo, Keytruda, Cyberknife

Outcome Measures

Primary Outcomes (2)

• 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)

  24 months

• 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.

  0-15 weeks

Secondary Outcomes (4)

• Progression Free Survival

  3-24 Months

• Local Control

  0-24 Months

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

  6-24 Months

• Impact of Tumor Burden

  24 Months

Study Arms (1)

Treatment Arm

EXPERIMENTAL

Radiation: Stereotactic Body Radiotherapy

Interventions

Stereotactic Body Radiotherapy 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.

Also known as: SBRT, SRS, SABR, CyberKnife

Treatment Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Crozer-Keystone Health System: lead
• Saint Peters University Hospital: collaborator
• Community Medical Center, Toms River, NJ: collaborator

Study Sites (1)

Philadelphia CyberKnife

Philadelphia, Pennsylvania, 19083, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Radiosurgery

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 18, 2017
• First Posted: January 31, 2019
• Study Start: April 28, 2017
• Primary Completion: March 8, 2022
• Study Completion: March 8, 2022
• Last Updated: March 6, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)