Promoting Immunotherapy Efficacy With Low-Dose Liver RT

NCT07225036 | Recruiting DMC

• 1 other identifier: UCCC-RT-25-01
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to see if adding Low-Dose Liver Radiation (LD-LRT) improves progression free survival (PFS). This study is for patients with either melanoma or non-small cell lung cancer (NSCLC), with liver metastases, and receiving immunotherapy.

Conditions

Low-Dose Liver Radiation (LD-LRT); Non Small Cell Lung Cancer; Melanoma; Liver Metastases

Outcome Measures

Primary Outcomes (1)

• Progression free survival (PFS) measured by 6-month PFS for each cohort compared separately to historical trials with an effect size goal of 25% improvement in 6-month PFS

  The primary objective is to evaluate whether the addition of Low-Dose Liver Radiation (LD-LRT) improves progression free survival (PFS) in patients with melanoma and non-small cell lung cancer (NSCLC) with liver metastases receiving immunotherapy. The primary endpoint is 6-month PFS for each cohort compared separately to historical trials with an effect size goal of 25% improvement in 6-month PFS.

  6 months

Secondary Outcomes (1)

• Overall survival (OS) measured by time to death or last follow up

  Enrollment to death or last follow-up (up to 2.5 years)

Other Outcomes (2)

• Immune profiling of patient peripheral blood mononuclear cells (PBMCs)

  Baseline (Day -35), post-cycle 1 RT (Approx day 5), prior to cycle 2 RT (approx day 35), prior to cycle 3 RT (approx day 65), 3 months (approx day 90)

• TCR repertoire and clonal diversity in patients receiving LD-LRT and immunotherapy

  Baseline (Day -35), post-cycle 1 RT (Approx day 5), prior to cycle 2 RT (approx day 35), prior to cycle 3 RT (approx day 65), 3 months (approx day 90)

Study Arms (1)

LD-LRT

EXPERIMENTAL

Low-dose radiation to the liver the week prior to Cycles 1, 2 and 3 of systemic treatment.

Radiation: LD-LRT

Interventions

LD-LRT RADIATION

Low-dose radiation to the liver the week prior to Cycles 1, 2 and 3 of standard of care immunotherapy treatment.

LD-LRT

Eligibility Criteria

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

You may qualify if:

• Age ≥18 years.
• ECOG performance status ≤2 (or Karnofsky ≥60%, see Appendix A).
• Patients must have adequate organ and marrow function to receive standard of care immunotherapy and/or chemoimmunotherapy as per the treating medical oncologist.
• Must be planning to, and able to, undergo active treatment with PD-L1 or PD-1 checkpoint immunotherapy given per standard care throughout the duration of the RT intervention per their treating physician.
• Note: Patients may receive other SOC CTLA 4 inhibitors or other SOC chemotherapy/immunotherapy in combination with a SOC PD-L1 or PD-1 checkpoint inhibitor and remain eligible.
• Biopsy proven Non-Small Cell Lung Cancer (NSCLC) or Melanoma.
• Radiographic evidence of liver metastases.
• Women of child-bearing potential and men must agree to use adequate contraception (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation.
• Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants.
• Patients must have insurance authorization to proceed with radiotherapy prior to initiation of radiation treatment on study

You may not qualify if:

• Patients with prior immunotherapy use in the adjuvant setting for NSCLC or Melanoma are eligible unless the adjuvant immunotherapy was delivered within 6 months of enrollment.
• Patients with NSCLC are ineligible for enrollment in cohort 1 if the presence of the following driver mutations are noted: EGFR, ALK, ROS1, RET.
• Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make participation in this protocol unreasonably hazardous, in the opinion of the Investigator.
• Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen in the opinion of the Investigator.
• Pregnant women are excluded from this study considering the use of ionizing radiation.

Sponsors & Collaborators

• Jordan Kharofa: lead

Study Sites (1)

University of Cincinnati Medical Center

Cincinnati, Ohio, 45219, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Melanoma

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases

Central Study Contacts

UCCC Clinical Trials Office

CONTACT

513-584-7698; cancer@uchealth.com

Jordan Kharofa, MD

CONTACT

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Model Details: The trial will be conducted using Simon's optimal two-stage test in two separate cohorts. Cohort 1 will include patients with NSCLC with liver metastases. Cohort 2 will include patients with melanoma with liver metastases. The primary endpoint is 6-month PFS for each cohort compared separately to historical trials with an effect size goal of 25% improvement in 6-month PFS.

Study Record Dates

• First Submitted: October 29, 2025
• First Posted: November 5, 2025
• Study Start: December 15, 2025
• Primary Completion (Estimated): June 15, 2027
• Study Completion (Estimated): December 15, 2029
• Last Updated: February 27, 2026

Record last verified: 2026-02

Locations

US (1)