Promoting Immunotherapy Efficacy With Low-Dose Liver RT

Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18+
SponsorJordan Kharofa

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

Disqualifiers

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.

Trial design

Design model

Single group

Treatments tested in this trial

  • LD-LRT

    Radiation

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

Treatment groups

21 Participants
are divided into 1 treatment group
Group A: LD-LRTExperimental treatment 1 intervention

Trial outcomes

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.

Time frame
6 months

Secondary outcomes

1

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

The secondary objective is to evaluate whether the addition of Low-Dose Liver Radiation (LD-LRT) improves overall survival (OS) in patients with melanoma and non-small cell lung cancer (NSCLC) with liver metastases receiving immunotherapy. OS will be assessed as the time from enrollment to death or last follow-up.

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

Other outcomes

1

Immune profiling of patient peripheral blood mononuclear cells (PBMCs)

1\. To determine the immune profiling of patient peripheral blood mononuclear cells (PBMCs) for immunophenotype and activation status, and patient plasma for soluble immune/inflammatory mediators (i.e., cytokines) using flow cytometry-based and plasma based cytokine analysis.

Time frame
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)
2

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

2\. To evaluate T cell receptor (TCR) via TCR sequencing to characterize the TCR repertoire and clonal diversity in patients receiving LD-LRT and immunotherapy.

Time frame
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)

Sponsors and contacts

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Jordan Kharofa

Lead sponsor

University of Cincinnati

Sponsor institution