Low-Dose Liver Radiation for Melanoma or Lung Cancer

(PRIMT-LRT Trial)

Overseen By UCCC Clinical Trials Office

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Jordan Kharofa

Must be taking: PD-L1, PD-1 inhibitors

Disqualifiers: EGFR, ALK, ROS1, RET mutations, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

Duration: 3 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether adding Low-Dose Liver Radiation (LD-LRT) can help stop the spread of melanoma or non-small cell lung cancer (NSCLC) that has reached the liver. The goal is to determine if this approach, combined with standard immunotherapy, can extend the period during which the cancer does not worsen. Suitable participants have melanoma or NSCLC with liver involvement and are planning to start or continue checkpoint immunotherapy. As an unphased trial, this study offers a unique opportunity to contribute to innovative research that could enhance future cancer treatments.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you must be able to undergo treatment with certain immunotherapy drugs, so it's best to discuss your current medications with the trial team.

What prior data suggests that Low-Dose Liver Radiation is safe for patients with melanoma or non-small cell lung cancer?

Research shows that low-dose liver radiation (LD-LRT) is generally well-tolerated by patients. Studies have found that people receiving LD-LRT did not experience severe side effects or major health problems from the treatment.

Another study discovered that LD-LRT can cause temporary swelling in tumors, which might enhance the effectiveness of other treatments. Although this swelling might sound concerning, it is an expected part of the treatment to help fight cancer more effectively.

These findings suggest that LD-LRT is relatively safe for patients, with no major negative effects reported in the research. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about low-dose liver radiation (LD-LRT) because it takes a different approach to treating melanoma or lung cancer. While traditional treatments often involve high-dose radiation targeting tumors directly, LD-LRT uses a gentler dose aimed at the liver before systemic treatments. This technique could potentially enhance the body's response to cancer therapies by priming the liver, a key organ in processing drugs and immune responses. By integrating LD-LRT into the treatment plan, there's hope for improved efficacy and reduced side effects compared to conventional high-dose radiation.

What evidence suggests that Low-Dose Liver Radiation might be an effective treatment for melanoma or lung cancer?

Studies have shown that adding low-dose liver radiation (LD-LRT), which participants in this trial will receive, to immunotherapy might improve treatment outcomes for people with melanoma or non-small cell lung cancer (NSCLC) that has spread to the liver. One study found that combining low-dose radiation with immunotherapy increased the likelihood of tumor shrinkage, indicating a better response to treatment. Another study reported a case where low-dose radiation helped overcome resistance to immunotherapy in advanced melanoma, enhancing the treatment's effectiveness. These findings suggest that LD-LRT could enhance the effectiveness of immunotherapy, potentially leading to longer periods without cancer progression. ^{5 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for patients with melanoma or non-small cell lung cancer (NSCLC) who have cancer that has spread to the liver. Participants must be receiving immunotherapy and meet other health requirements set by the study.

Inclusion Criteria

Radiographic evidence of liver metastases

Ability to understand and the willingness to sign a written informed consent document

My insurance has approved my radiotherapy treatment.

Exclusion Criteria

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

I had immunotherapy for lung or skin cancer but not in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive standard of care immunotherapy with or without chemotherapy, and Low-Dose Liver Radiation (LD-LRT) is administered before cycles 1, 2, and 3 of treatment

3 months

3 visits for LD-LRT administration

Follow-up

Participants are monitored for progression free survival (PFS) and overall survival (OS)

6 months for PFS, up to 2.5 years for OS

Immune Profiling

Immune profiling of patient peripheral blood mononuclear cells (PBMCs) and plasma for immune/inflammatory mediators

3 months

Multiple visits for blood sampling

What Are the Treatments Tested in This Trial?

Interventions

• Low-Dose Liver Radiation (LD-LRT)

Trial Overview The trial is testing whether adding Low-Dose Liver Radiation Therapy (LD-LRT) can extend the time without cancer progression in patients already undergoing immunotherapy for melanoma or NSCLC with liver metastases.

How Is the Trial Designed?

Group I: LD-LRT Experimental Treatment 1 Intervention

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

Who Is Running the Clinical Trial?

Jordan Kharofa

Lead Sponsor

Trials

2

Recruited

10+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11781074/

Enhancing immunotherapy efficacy with synergistic low ... These findings underscore the promise of combining low-dose radiotherapy with immunotherapy, highlighting the potential for improved outcomes ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8714746/

Novel Use of Low-Dose Radiotherapy to Modulate ... For example, rates of liver metastases are high for uveal melanoma (~50%) (3, 4), colorectal cancer (30-50%), pancreatic adenocarcinoma (30-40%), and ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0360301625045080

Low-dose Radiation Therapy Concurrent With ... The 3-year OS rates were 57.4% and 18.8% in patients above and below the median depth of tumor response, respectively (hazard ratio, 0.28; 95% ...

4. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2025.1483117/full

Case report: Low-dose radiation reverses pembrolizumab ... We report a case of metastatic melanoma which demonstrated a reversal of immunotherapy resistance after the addition of low-dose radiotherapy to ...

5. thegreenjournal.com thegreenjournal.com/article/S0167-8140(23)00156-1/pdf

Five-year overall survival with ipilimumab and stereotactic ... Purpose: Ipilimumab plus stereotactic ablative radiotherapy (SABR) demonstrate satisfactory short-term clinical benefit and low toxicities ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S2452109425000296

Prospective Study of Patients Treated with Palliative ... No grade 3 or higher toxicity was attributable to combined treatment. The median survival for the cohort was 11 months. At 3 months, 26 patients had imaging ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10000719/

Low-Dose Radiation Therapy (LDRT) against Cancer and ... Follow-up showed that adding LDRT to HDRT strengthened the 4-month disease control response (47% in HDRT + LDRT versus 37% in HDRT alone; p = ...

8. jeccr.biomedcentral.com jeccr.biomedcentral.com/articles/10.1186/s13046-025-03281-2

Enhancing immunotherapy efficacy with synergistic low-dose ... Low-dose radiation therapy (LDRT) has demonstrated the capacity to transiently induce inflammation within tumors, rendering them more conducive ...

9. aacrjournals.org aacrjournals.org/clincancerres/article/29/20/4098/729404/Safety-and-Tolerability-of-Low-Dose-Radiation-and

Safety and Tolerability of Low-Dose Radiation and ... The objective response rate and disease control rate were 60.7% and 78.6%, respectively, and the median progression-free survival (PFS) was 8.6 months. Both ...