Head and Neck CancerPhase 2NCT07770100
Concurrent Immunotherapy and Systemic Therapy With Stereotactic Body Radiation Therapy (SBRT) for Stage IV Cancers (COINSSS IV)
A Phase 2 study testing Stereotactic Body Radiation Therapy (SBRT), Pembrolizumab and Nivolumab in people with Head and Neck Cancer and Non-Small Cell Lung Cancer, run by Mark Bernard at 1 site in United States.
Trial summary
This is a Phase II clinical study for people with stage IV cancer. The study will evaluate the use of stereotactic body radiation therapy (SBRT), a type of focused radiation treatment, together with immunotherapy-based treatment. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Head and Neck Cancer, Non-Small Cell Lung Cancer, Cervical Cancer
- What is being tested?
- Stereotactic Body Radiation Therapy (SBRT), Pembrolizumab and Nivolumab
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 1 siteUnited States
- Study dates
- 9 Sep 2026to 28 Feb 2040
- Phase
- Phase 2
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 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically proven advanced or stage IV head \& neck, non-small cell lung cancer, cervical, esophageal, gastric, and gastroesophageal cancer at least 6 metastases that are eligible for SBRT comprising: lung, liver, adrenal glands, bone, and lymph node sites with at least 1 other lesion meeting RECIST criteria of which this additional lesion not be treated with SBRT (biopsies performed for diagnosis are standard of care).
- At least 6 metastases eligible for SBRT comprising: lung, liver, adrenal glands, bone, and lymph node sites
- The 1 irradiated lesion must have a max point dose of 5Gy or less.
- Eligible for Immunotherapy for an FDA-approved indication as defined in section 6.1. NOTE: No limit is placed on prior systemic treatment unless it affects the eligibility for administration of immune checkpoint inhibitor therapy.
- If prior treatment with chemotherapy or radiotherapy or surgery has occurred: Prior chemotherapy or radiation must have concluded > 21 days prior to the start of study treatment. Exception: study treatment can start within 2-3 days following GKS [gamma knife surgery] or whole brain radiation therapy [ WBRT], as long as patient is not experiencing ongoing/residual AE's related to GKS or WBRT at discretion of treating physician.
- First Line immunotherapy-based treatments only. The patient may have received prior cycles of immunotherapy, but has to be on the first line of immunotherapy-based treatments.
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- If non-small cell lung cancer patient with pembrolizumab, PD-L1 testing CPS score > or = to 50% will have to be shown
- If cervical cancer patient on secondary line therapy with pembrolizumab, CPS score of > or = to 1 will have to be done. Please note, second line therapy with pembrolizumab is only allowed if the patient's first line of therapy did NOT include immunotherapy.
- If non-small cell lung cancer on first line ipilimumab in combination with nivolumab, PD-L1 of 1% and negative epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumor aberrations.
- If pembrolizumab is given for a gastric cancer, a PD-L1 expression (CPS =1) will need to be shown
- If pembrolizumab is given as a single agent treatment after progression of one prior systemic therapy agent for esophageal or gastroesophageal squamous cell carcinoma histology, a PD-L1 (CPS=1) expression will have to be shown.
- ECOG Performance Status 0 - 1 (see Appendix A).
- Life expectancy > or equal to 6 months.
- Adequate organ and bone marrow function prior to study treatment as defined by: Thresholds for lab values prior to initiation of study treatment.
- ANC > or equal to 1,000/mm3
- Platelets > or equal to 100,000/mm3
- Total bilirubin < or equal to or equal to 1.5 x ULN
- AST and ALT - With hepatic metastasis, < or equal to or equal to 5 x ULN. If no hepatic metastasis, < or equal to 2.5 times x ULN
- Creatinine Or Creatinine Clearance < or equal to 1.5 x ULNand/or CrCl > or equal to 30ml/min (per 24-hour urine collection) or calculated according to the Cockcroft-Gault formula (Appendix B)
- 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.
- 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 methods prescribed their the patients primary care physician, urologist, or obstetrician/gynecologist 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
- Presence of < or equal to 5 sites amenable to SBRT
- Ineligible for immune checkpoint inhibitors based on package insert of the chosen immune checkpoint inhibitor
- No more than 7 metastatic sites to an organ, defined as liver, left lung, right lung, single anatomically bone site (e.g. femur, humerus, single vertebral body).
- NOTE: Multiple different vertebral bodies are allowed.
- Peritoneal involvement, at the discretion of the study PI. NOTE: Peritoneal metastasis does not exclude GI nor cervical cancer, except in cases where there is a separate focus of spread to the peritoneum.
- Presence of liver cirrhosis of any grade prohibits SBRT to the liver. NOTE: Pt can enroll to trial if receiving SBRT to other non-liver metastatic sites.
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- A plan that cannot meet organ at risk tolerance (as defined in section 6.7.2.1) Auto-immune diagnosis Medications prohibited while receiving concurrent SBRT: gemcitabine, Adriamycin, VEGF or BRAF inhibitors.
- NOTE: However, if the patient is on the prohibited agent(s), the patient is still eligible for the trial so long as the prohibited agent can safely be held for at least 1 month before starting SBRT, during SBRT, and 1 month after completion of SBRT.
- -Major surgical procedure (including craniotomy and open brain biopsy) or significant traumatic injury (injury requiring immediate surgical intervention or involving loss of consciousness) within 14 days prior to registration or those patients who receive a nonCNS minor surgical procedures (e.g. core biopsy or fine needle aspiration) within 3 days prior to registration.
- NOTE: 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.
- Active clinically serious infection > CTCAE Grade 2.
- Serious non-healing wound, ulcer or bone fracture.
- 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; 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.
- Receipt of live attenuated vaccine within 30 days prior to the first dose of ICI.
- Note: Patients, if randomized, should not receive live vaccine while receiving ICI and up to 30 days after the last dose of ICI.
- -Inclusion of Women and Minorities - Consistent with NIH policy, both men and women of all races and ethnic groups are eligible for this trial.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Kentucky Markey Cancer Center
Lexington, Kentucky, 40536
Mark Bernard, 8592577618, mark.bernard@uky.edu
About this study
This is a Phase II clinical study for people with stage IV cancer. The study will evaluate the use of stereotactic body radiation therapy (SBRT), a type of focused radiation treatment, together with immunotherapy-based treatment. SRBT will be used to treat multiple areas of cancer that have spread to other parts of the body. The study will evaluate whether this treatment approach can be safely given while patients continue their planned cancer treatment and may help control their cancer.
- Conditions
- Head and Neck Cancer, Non-Small Cell Lung Cancer, Cervical Cancer, Esophageal Cancer, Gastric Cancer (GC)
- Being tested
- Stereotactic Body Radiation Therapy (SBRT), Pembrolizumab, Nivolumab, Atezolizumab, Ipilimumab
- Medical subject headings
- Head and Neck Neoplasms, Carcinoma, Non-Small-Cell Lung, Uterine Cervical Neoplasms, Esophageal Neoplasms, Stomach Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Stereotactic Body Radiation Therapy (SBRT)Radiation
SBRT administered to 6-10 metastatic lesions during the first cycle of immunotherapy.
PembrolizumabDrug
FDA-approved immune checkpoint inhibitor administered according to standard clinical practice and disease-specific indications.
NivolumabDrug
FDA-approved immune checkpoint inhibitor administered according to standard clinical practice and disease-specific indications.
AtezolizumabDrug
FDA-approved immune checkpoint inhibitor administered according to clinical practice and disease-specific indications.
IpilimumabDrug
FDA-approved immune checkpoint inhibitor administered according to standard clinical practice and disease-specific indications.
| Study group | Role | What they receive |
|---|---|---|
| Concurrent Immunotherapy and SBRT | Experimental | Participants receive standard-of-care immune checkpoint inhibitor therapy and concurrent stereotactic body radiation therapy (SBRT) to 6-10 metastatic lesions. Receives: Radiation: Stereotactic Body Radiation Therapy (SBRT); Drug: Pembrolizumab; Drug: Nivolumab; Drug: Atezolizumab; Drug: Ipilimumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
6-Month Progression-Free Survival (PFS)
Progression-Free Survival (PFS) measured from study enrollment until disease progression or death from any cause.
Measured: 6 Months
Secondary outcomes (6)
Acute Grade 2 or Higher Toxicity
Number of participants experiencing Grade 2 or higher adverse events according to CTCAE version 6.0.
Measured: Up to 1 Year
Overall Survival
Overall survival from study enrollment.
Measured: 1 Year
Local Recurrence-Free Survival
Time from study enrollment to local recurrence.
Measured: 1 Year
Distant Metastasis Progression-Free Survival
Time from study enrollment to distant metastatic progression.
Measured: 1 Year
Objective Response Rate
Tumor response rate assessed using iRECIST criteria.
Measured: 1 Year
Continuation of Systemic Therapy
Proportion of participants continuing planned systemic therapy without interruption attributable to SBRT. Interruption is defined as cessation of immunotherapy administration lasting 30 days or more.
Measured: 1 Year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Aug 2026
- Study start9 Sep 2026
- Primary completion28 Feb 2040 (estimated)
- Study completion28 Feb 2040 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Head and Neck 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
- 35 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Mark Bernard
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Mark Bernard, University of Kentucky
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07770100
- Sponsor's protocol ID
- 113272
- Status last verified
- Oct 2026
- First submitted
- 10 Aug 2026
- Last updated
- 14 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No