Priming Immunotherapy in Advanced Disease With Radiation

NCT03313804 | Completed Phase 2 Results FDA Drug FDA Device

• 1 other identifier: MCC-17-MULTI-20-PMC
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Squamous Cell Carcinoma of the Head and Neck; Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• 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.

  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.

  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.

  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

  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

Study Arms (1)

Immune Checkpoint Inhibitor + Radiation

EXPERIMENTAL

Immune checkpoint inhibitor (Nivolumab OR Pembrolizumab OR Atezolizumab) PLUS Radiation Therapy (Stereotactic Body Radiation Therapy OR fractionated radiation therapy)

Drug: Immune checkpoint inhibitor; Radiation: Radiation Therapy

Interventions

Radiation Therapy RADIATION

Stereotactic Body Radiation Therapy OR Fractionated radiation therapy

Immune Checkpoint Inhibitor + Radiation

Immune checkpoint inhibitor DRUG

Standard of care immune checkpoint inhibitor

Immune Checkpoint Inhibitor + Radiation

Eligibility Criteria

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

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• John L. Villano, MD, PhD: lead

Study Sites (1)

University of Kentucky Markey Cancer Center

Lexington, Kentucky, 40536, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Squamous Cell Carcinoma of Head and Neck

Interventions

Immune Checkpoint Inhibitors; Radiotherapy

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Head and Neck Neoplasms

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses; Therapeutics

Results Point of Contact

• Title: Dr. John Villano
• Organization: University of Kentucky

jlvillano@uky.edu

8593234405

Study Officials

• John Villano, MD, PhD

  University of Kentucky

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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: Principal Investigator

Study Record Dates

• First Submitted: September 29, 2017
• First Posted: October 18, 2017
• Study Start: October 26, 2017
• Primary Completion: February 16, 2024
• Study Completion: February 16, 2026
• Last Updated: March 11, 2026
• Results First Posted: April 6, 2025

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)