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
|Condition or disease||Intervention/treatment||Phase|
|Metastatic Nonsmall Cell Lung Cancer Non Small Cell Lung Cancer||Radiation: Stereotactic Body Radiotherapy||Not Applicable|
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)|
|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|
|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.
- 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)
- 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.
- 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
- 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
- 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
- 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
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
|Contact: Shilecion Cooperfirstname.lastname@example.org|
|United States, Pennsylvania|
|Philadelphia, Pennsylvania, United States, 19083|
|Contact: Michael Good 610-446-5860 email@example.com|