Priming Immunotherapy in Advanced Disease With Radiation
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|ClinicalTrials.gov Identifier: NCT03313804|
Recruitment Status : Recruiting
First Posted : October 18, 2017
Last Update Posted : October 26, 2018
This study proposes to treat metastatic non-small cell lung cancer (NSCLC) and head/neck squamous cell cancer (HNSCC) patients who are already initiating an immune checkpoint inhibitor (such as Nivolumab, Atezolizumab or Pembrolizumab) for disease treatment as per FDA approved guidelines. In these patients we will deliver a short-course radiation to a single systemic (non-CNS) site within 14 days of receiving the first dose of immune checkpoint inhibitors. This sequence allows radiation to release tumor antigens from immune inaccessible areas such as necrotic tumor or low perfusion to provide a robust anti-tumor immune response with immune checkpoint inhibitors.
The primary objective is to assess six-month progression free survival (PFS) compared to historical control.
|Condition or disease||Intervention/treatment||Phase|
|Non-small Cell Lung Cancer Squamous Cell Carcinoma of the Head and Neck||Drug: Immune checkpoint inhibitor Radiation: Radiation Therapy||Phase 2|
Subjects with front-line or relapsed NSCLC or relapsed HNSCC who are intended to receive standard of care immune checkpoint inhibitors without a contraindication to Stereotactic Body Radiation Therapy (SBRT) to a single cancer deposit greater than 1 cm (metastasis or primary cancer) will be enrolled. Subjects will receive standard of care (SOC) immune checkpoint inhibitors and within 2 weeks of initiation, and will receive either:
- SBRT to target to achieve Biological Equivalent Dose (BED) > 100 Gy OR
- 30 Gy fractionated radiation therapy (RT) delivered as a 3 dimensional (3-D) dose.
The lesion choice will be made by the treating radiation oncologist and will be directed to a single malignant focus (non-CNS) that measures ≥ 1 cm. Essentially, the goals of both techniques are the same but SBRT is reserved for lesions that are readily encompassed by a single field with large RT fractions in which dose-limiting organs are within safe limits.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||57 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Priming Immunotherapy in Advanced Disease With Radiation|
|Actual Study Start Date :||October 26, 2017|
|Estimated Primary Completion Date :||June 30, 2019|
|Estimated Study Completion Date :||June 30, 2028|
Experimental: Immune Checkpoint Inhibitor + Radiation
Immune checkpoint inhibitor (Nivolumab OR Pembrolizumab OR Atezolizumab) PLUS Radiation Therapy (Stereotactic Body Radiation Therapy OR fractionated radiation therapy)
Drug: Immune checkpoint inhibitor
Standard of care immune checkpoint inhibitor
Radiation: Radiation Therapy
Stereotactic Body Radiation Therapy OR Fractionated radiation therapy
- The primary study endpoint is 6-month progression-free survival. [ Time Frame: 6-months post enrollment ]Progression-free survival will be calculated as time from enrollment in the study to progression at 6-months post enrollment.
- Percentage of (programmed death) PD-1+ CD4+ T (helper) cells and PD-1+ CD8+ T (cytotoxic) cells prior to treatment versus with concurrent treatment. [ Time Frame: Assessed at specified points--1) prior to each cycle of therapy for 4 cycles (one cycle equals 6 weeks) 2) at disease progression (date first progression post-randomization, assessed up to 3 years) 3) when participant is off-study, assessed up to 3 years ]
- Percentage of CD8+ T-cells that are gamma-interferon positive during treatment. [ Time Frame: Assessed at specified points--1) prior to each cycle of therapy for 4 cycles (one cycle equals 6 weeks) 2) at disease progression (date first progression post-randomization, assessed up to 3 years) 3) when participant is off-study, assessed up to 3 years ]
- Percentage PD-L1+ CD4+ and PD-L1+ CD8+ T-cell expression differences during treatment [ Time Frame: Assessed at specified points--1) prior to each cycle of therapy for 4 cycles (one cycle equals 6 weeks) 2) at disease progression (date first progression post-randomization, assessed up to 3 years) 3) when participant is off-study, assessed up to 3 years ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03313804
|Contact: John Villano, MD, PhDfirstname.lastname@example.org|
|United States, Kentucky|
|University of Kentucky Markey Cancer Center||Recruiting|
|Lexington, Kentucky, United States, 40536|
|Contact: John Villano, MD, PhD 859-323-0405 email@example.com|
|Principal Investigator:||John Villano, MD, PhD||University of Kentucky|