Concurrent Immunotherapy and Systemic Therapy With Stereotactic Body Radiation Therapy (SBRT) for Stage IV Cancers (COINSSS IV)

NCT07770100 | Not Yet Recruiting Phase 2 FDA Drug

• 1 other identifier: 113272
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief 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. 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)

Outcome Measures

Primary Outcomes (1)

• 6-Month Progression-Free Survival (PFS)

  Progression-Free Survival (PFS) measured from study enrollment until disease progression or death from any cause.

  6 Months

Secondary Outcomes (6)

• Acute Grade 2 or Higher Toxicity

  Up to 1 Year

• Overall Survival

  1 Year

• Local Recurrence-Free Survival

  1 Year

• Distant Metastasis Progression-Free Survival

  1 Year

• Objective Response Rate

  1 Year

Study Arms (1)

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.

Radiation: Stereotactic Body Radiation Therapy (SBRT); Drug: Pembrolizumab; Drug: Nivolumab; Drug: Atezolizumab; Drug: Ipilimumab

Interventions

Stereotactic Body Radiation Therapy (SBRT) RADIATION

SBRT administered to 6-10 metastatic lesions during the first cycle of immunotherapy.

Concurrent Immunotherapy and SBRT

Pembrolizumab DRUG

FDA-approved immune checkpoint inhibitor administered according to standard clinical practice and disease-specific indications.

Concurrent Immunotherapy and SBRT

Nivolumab DRUG

FDA-approved immune checkpoint inhibitor administered according to standard clinical practice and disease-specific indications.

Concurrent Immunotherapy and SBRT

Atezolizumab DRUG

FDA-approved immune checkpoint inhibitor administered according to clinical practice and disease-specific indications.

Concurrent Immunotherapy and SBRT

Ipilimumab DRUG

FDA-approved immune checkpoint inhibitor administered according to standard clinical practice and disease-specific indications.

Concurrent Immunotherapy and SBRT

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Mark Bernard: lead

Study Sites (1)

University of Kentucky Markey Cancer Center

Lexington, Kentucky, 40536, United States

Location

MeSH Terms

Conditions

Head and Neck Neoplasms; Carcinoma, Non-Small-Cell Lung; Uterine Cervical Neoplasms; Esophageal Neoplasms; Stomach Neoplasms

Interventions

Radiosurgery; pembrolizumab; Nivolumab; atezolizumab; Ipilimumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Mark Bernard, MD

CONTACT

8592577618; mark.bernard@uky.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: August 10, 2026
• First Posted: August 18, 2026
• Study Start: October 1, 2026
• Primary Completion (Estimated): February 28, 2040
• Study Completion (Estimated): February 28, 2040
• Last Updated: August 20, 2026

Record last verified: 2026-08

Locations

US (1)