Non-small Cell Lung CancerPhase 2NCT03313804
Priming Immunotherapy in Advanced Disease With Radiation
A Phase 2 study testing Immune checkpoint inhibitor and Radiation Therapy in people with Non-small Cell Lung Cancer and Squamous Cell Carcinoma of the Head and Neck, run by John L. Villano, MD, PhD at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-small Cell Lung Cancer, Squamous Cell Carcinoma of the Head and Neck
- What is being tested?
- Immune checkpoint inhibitor and Radiation Therapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 76 participants
- Where
- 1 siteUnited States
- Study dates
- 26 Oct 2017to 16 Feb 2026
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically proven advanced or metastatic non-small cell lung cancer or squamous cell carcinoma head and neck with tumor at least 1 cm in size.
- Eligible for treatment with radiation therapy.
- Prior treatment: chemotherapy or radiotherapy or surgery.
- Prior chemotherapy or radiation must have concluded ≥ 21 days prior to the start of study treatment.
- No limit is placed on prior systemic treatment, but subjects must be eligible for immune checkpoint inhibitors therapy, for an FDA approved indication.
- No major surgery within 14 days of start of study treatment.
Show all 18Show fewer
- No previous or concurrent malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease free for the past 3 years.
- Age ≥ 18 years.
- Life expectancy ≥ 3 months.
- Required initial laboratory values:
- Absolute neutrophil count ≥ 1,000/mm3
- Platelets ≥ 100,000/mm3
- Total bilirubin ≤ 1.5 x ULN
- AST and ALT if no hepatic metastasis ≤ 2.5 times x ULN
- AST and ALT with hepatic metastasis ≤ 5 x ULN
- Creatinine ≤ 1.5 x ULN and Requires CrCl ≥ 60ml/min (per 24-hour urine collection or calculated according to the Cockcroft-Gault formula)
- Non pregnant and non-nursing women. Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment. Women of childbearing potential and men must agree to use adequate contraception (barrier method of birth control) prior to study entry and for the duration of study participation. Subjects should use adequate birth control for at least 3 months after the last administration of immune checkpoint inhibitors.
- Ability to understand and the willingness to sign a written informed consent document.
Who cannot join
- Active clinically serious infection > CTCAE Grade 2.
- Serious non-healing wound, ulcer or bone fracture.
- Prior treatment with immune checkpoint inhibitors.
- Ineligible for immune checkpoint inhibitors based on package insert of the chosen immune checkpoint inhibitor (e.g., uncontrolled immunologic disorders, active hepatitis, active colitis, active pneumonitis, uncontrolled/active hormone gland problems - including thyroid, pituitary, adrenal glands and pancreas).
- Major surgical procedure (including craniotomy and open brain biopsy) or significant traumatic injury within 14 days prior to registration or those patients who receive a non-CNS minor surgical procedures (e.g. core biopsy or fine needle aspiration) within 3 days prior to registration. There is no waiting period for central line placement. There is a 7-day window for recovery prior to registration for patients who underwent stereotactic biopsy of the brain.
- Participants may not have uncontrolled inter-current illness. This includes, but is not limited to: ongoing or active infection; symptomatic congestive heart failure (NYHA class III or IV); unstable angina pectoris or new onset angina that began within the last 3 months; cardiac ventricular arrhythmias requiring anti-arrhythmic therapy; or thrombotic/embolic events such as cerebrovascular accident, including transient ischemic attacks within the past 6 months. Uncontrolled hypertension defined as systolic blood pressure >150 mmHg or diastolic pressure > 90 mmHg, despite optimal medical management. Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C. Known Grade 3 or 4 neurotoxicity.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Kentucky Markey Cancer Center
Lexington, Kentucky, 40536
About this study
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.
Read the detailed description
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.
- Being tested
- Immune checkpoint inhibitor, Radiation Therapy
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Squamous Cell Carcinoma of Head and Neck
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Immune checkpoint inhibitorDrug
Standard of care immune checkpoint inhibitor
Radiation TherapyRadiation
Stereotactic Body Radiation Therapy OR Fractionated radiation therapy
| Study group | Role | What they receive |
|---|---|---|
| Immune Checkpoint Inhibitor + Radiation | Experimental | Immune checkpoint inhibitor (Nivolumab OR Pembrolizumab OR Atezolizumab) PLUS Radiation Therapy (Stereotactic Body Radiation Therapy OR fractionated radiation therapy) Receives: Drug: Immune checkpoint inhibitor; Radiation: Radiation Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of Participants Alive and Without Progression
Progression-free survival will be calculated as a rate, time from enrollment in the study to progression at 6-months post enrollment.
Measured: 6-months post enrollment
Secondary outcomes (3)
Percentage of (Programmed Death) PD-1+ CD4+ T (Helper) Cells and PD-1+ CD8+ T (Cytotoxic) Cells Prior to Treatment Versus With Concurrent Treatment.
Measured: 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.
Measured: 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
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2017
- Study start26 Oct 2017
- Primary completion16 Feb 2024
- Study completion16 Feb 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Non-small Cell Lung CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 76 participants (actual)
Sponsor and investigators
- Lead sponsor
- John L. Villano, MD, PhD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, John L. Villano, MD, PhD, University of Kentucky
- Investigators
- John Villano, MD, PhD, Principal investigator, University of Kentucky
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03313804
- Sponsor's protocol ID
- MCC-17-MULTI-20-PMC
- Status last verified
- Feb 2026
- First submitted
- 29 Sep 2017
- Last updated
- 11 Mar 2026
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Priming Immunotherapy in Advanced Disease With Radiation
- ClinicalTrials.gov ID
- NCT03313804
- Acronym / sponsor ID
- MCC-17-MULTI-20-PMC
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 76 participants (actual)
- Lead sponsor
- John L. Villano, MD, PhDUniversity, hospital or other
- Study start
- 26 Oct 2017 (actual)
- Primary completion
- 16 Feb 2024 (actual)
- Study completion
- 16 Feb 2026 (actual)
- First posted
- 18 Oct 2017 (actual)
- Results
- Posted 6 Apr 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Immune Checkpoint Inhibitor + Radiation | Experimental | Drug: Immune checkpoint inhibitor, Radiation: Radiation TherapyImmune checkpoint inhibitor (Nivolumab OR Pembrolizumab OR Atezolizumab) PLUS Radiation Therapy (Stereotactic Body Radiation Therapy OR fractionated radiation therapy) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Histologically proven advanced or metastatic non-small cell lung cancer or squamous cell carcinoma head and neck with tumor at least 1 cm in size.
- Eligible for treatment with radiation therapy.
- Prior treatment: chemotherapy or radiotherapy or surgery.
- No previous or concurrent malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease free for the past 3 years.
- Age ≥ 18 years.
Key exclusion criteria (6 listed)
- Active clinically serious infection > CTCAE Grade 2.
- Serious non-healing wound, ulcer or bone fracture.
- Prior treatment with immune checkpoint inhibitors.
- Ineligible for immune checkpoint inhibitors based on package insert of the chosen immune checkpoint inhibitor (e.g., uncontrolled immunologic disorders, active hepatitis, active colitis, active pneumonitis, uncontrolled/active hormone gland problems - including thyroid, pituitary, adrenal glands and pancreas).
- Major surgical procedure (including craniotomy and open brain biopsy) or significant traumatic injury within 14 days prior to registration or those patients who receive a non-CNS minor surgical procedures (e.g. core biopsy or fine needle aspiration) within 3 days prior to registration. There is no waiting period for central line placement. There is a 7-day window for recovery prior to registration for patients who underwent stereotactic biopsy of the brain.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Immune checkpoint inhibitorStandard of care immune checkpoint inhibitor | Drug | Immune Checkpoint Inhibitor + Radiation |
| Radiation TherapyStereotactic Body Radiation Therapy OR Fractionated radiation therapy | Radiation | Immune Checkpoint Inhibitor + Radiation |
Primary outcome
Proportion of Participants Alive and Without Progression
Time frame: 6-months post enrollment
Progression-free survival will be calculated as a rate, time from enrollment in the study to progression at 6-months post enrollment.
3 secondary outcomes
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Mar 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
John Villano, MD, PhD principal investigator
University of Kentucky
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Immune checkpoint inhibitor and Radiation Therapy in people with Non-small Cell Lung Cancer and Squamous Cell Carcinoma of the Head and Neck, run by John L. Villano, MD, PhD at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Apr 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of Participants Alive and Without Progression (time frame: 6-months post enrollment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Mar 2026.