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

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ClinicalTrials.gov Identifier: NCT03825510
Recruitment Status : Recruiting
First Posted : January 31, 2019
Last Update Posted : January 31, 2019
Sponsor:
Collaborators:
Saint Peter's University Hospital, New Brunswick, NJ
Community Medical Center, Toms River, NJ
Information provided by (Responsible Party):
Olusola Obayomi-Davies M.D., Crozer-Keystone Health System

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.

Condition or disease Intervention/treatment Phase
Metastatic Nonsmall Cell Lung Cancer Non Small Cell Lung Cancer Radiation: Stereotactic Body Radiotherapy Not Applicable

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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : April 28, 2017
Estimated Primary Completion Date : August 28, 2019
Estimated Study Completion Date : August 28, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arm Intervention/treatment
Experimental: Treatment Arm Radiation: 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.

Other Names:
  • SBRT
  • SRS
  • SABR
  • CyberKnife




Primary Outcome Measures :
  1. Overall Survival [ Time Frame: 24 months ]
    Determine overall survival in patients receiving SBRT and immunotherapy as compared to landmark trials of patients receiving immunotherapy alone (Checkmate 057, Keynote 024)

  2. Acute Toxicity: Radiation pnuemonitis measured using NCI CTCAE version 4.0 [ Time Frame: 0-15 weeks ]
    Determine excess/unexpected toxicity that cannot be attributed to routine radiation therapy or immunotherapy side effects.


Secondary Outcome Measures :
  1. Progression Free Survival [ Time Frame: 3-24 Months ]
    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

  2. Local Control [ Time Frame: 0-24 Months ]
    To determine the local control measured from time of enrollment to first evidence of progressive disease at the treatment site

  3. Late Toxicity: Pulmonary, Bone or Visceral organ toxicity evaluated 6 months from completion of treatment using NCI CTCAE version 4. [ Time Frame: 6-24 Months ]
    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

  4. Impact of Tumor Burden [ Time Frame: 24 Months ]
    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



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03825510


Contacts
Contact: Shilecion Cooper 610-446-6850 smcooper@allianceoncology.com

Locations
United States, Pennsylvania
Philadelphia CyberKnife Recruiting
Philadelphia, Pennsylvania, United States, 19083
Contact: Michael Good    610-446-5860    michael.good@corzer.org   
Sponsors and Collaborators
Crozer-Keystone Health System
Saint Peter's University Hospital, New Brunswick, NJ
Community Medical Center, Toms River, NJ

Responsible Party: Olusola Obayomi-Davies M.D., Principal Investigator, Crozer-Keystone Health System
ClinicalTrials.gov Identifier: NCT03825510     History of Changes
Other Study ID Numbers: CKHS 17-009
First Posted: January 31, 2019    Key Record Dates
Last Update Posted: January 31, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No
Pediatric Postmarket Surveillance of a Device Product: No

Keywords provided by Olusola Obayomi-Davies M.D., Crozer-Keystone Health System:
Opdivo, Keytruda, Cyberknife

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms