A Phase 2 interventional study of Biospecimen Collection and Cholecalciferol in Advanced Hepatocellular Carcinoma, Advanced Melanoma and Locally Advanced Melanoma, sponsored by University of Southern California. Not yet recruiting at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-23.
Sponsored by University of Southern California · Phase 2, Interventional, and Treatment
This clinical trial tests the effect of multiple therapies (propranolol, desloratadine, and magnesium and vitamin D supplements) added to primary standard of care immunotherapy (adjunct), as well as adjusting the timing of standard immunotherapy to a morning infusion, in treating patients with melanoma that has spread to nearby tissue or lymph nodes (locally advanced) or that has spread from where it first started to other places in the body (metastatic) or hepatocellular cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Propranolol is a medication used for high blood pressure. Desloratadine is a type of drug that blocks the action of histamines, which can cause fever, itching, sneezing, a runny nose, and watery eyes. Immunotherapy has been approved for multiple kinds of advanced cancers, including melanoma, kidney cancer, non-small cell lung cancer and hepatocellular (liver) cancer. Research suggests that giving propranolol and desloratadine, along with ensuring adequate levels of magnesium and vitamin D, as well as administering immunotherapy infusions in the morning may shrink or stop the spread of advanced cancers better than immunotherapy alone.
PRIMARY OBJECTIVE:
I. Compare levels of biomarkers of immunomodulation, specifically interleukin (IL)-8, interferon gamma (IFN-y), effector T cells (Teff)/regulatory T cell (Treg) ratio, over a 12-week period, in peripheral blood of patients undergoing standard of care PD-1/PD-L1-containing immunotherapy regimens for advanced cancers randomized to Arm A or Arm B.
SECONDARY OBJECTIVE:
I. Evaluate the safety and tolerability of the combination of: magnesium, vitamin D supplements; desloratadine; propranolol in patients undergoing morning infusion of standard of care PD-1/PD-L1-containing immunotherapy regimens in Arm A.
EXPLORATORY OBJECTIVES:
I. Compare additional biomarkers of immunomodulation (including [incl.] cytokines, metabolites, select metal ion levels, flow cytometry, circulating tumor deoxyribonucleic acid [ctDNA]) over a 12-week period, in peripheral blood of patients undergoing standard of care PD-1/PD-L1-containing immunotherapy regimens for advanced cancers randomized to Arm A or Arm B.
II. Compare the preliminary clinical benefit using time to next treatment (TTNT) in patients undergoing standard of care PD-1/PD-L1-containing immunotherapy regimens for advanced cancers randomized to Arm A or Arm B.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM A: Patients receive standard of care PD-1/PD-L1-containing immunotherapy infusion, starting before 12 PM, desloratadine orally (PO) once daily (QD), propranolol PO twice daily (BID), magnesium intravenously (IV) if magnesium level is below 1.9, and vitamin D PO QD if vitamin D level is below 30. Additional IV or oral magnesium and vitamin D supplementation may be administered at the investigator's discretion per standard of care. Treatment is given in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT) scan or magnetic resonance imaging (MRI) and blood sample collection throughout the study.
ARM B: Patients receive standard of care PD-1/PD-L1-containing immunotherapy, starting at standard of care time. Magnesium and vitamin D levels are checked with any supplementation per investigator discretion and institutional practice, without a prespecified goal level. Treatment is given in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan or MRI and blood sample collection throughout the study.
After completion of study treatment, patients are followed up every 3 months.
Non-childbearing potential is defined as:
Acceptable highly effective birth control methods include:
Sexual abstinence. In the context of this study sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse from the start of therapy through 90 days after the completion of therapy
Exclusion Criteria:
A known history or autoimmune disease requiring systemic immunosuppressive therapy; or any disease process requiring systemic immunosuppressive therapy (e.g. high-dose steroids defined as ≥ 10 mg prednisone or equivalent per day).
Has active central nervous system (CNS) metastases and/or any history of leptomeningeal disease
Patients receive standard of care PD-1/PD-L1-containing immunotherapy infusion, starting before 12 PM, desloratadine PO QD, propranolol PO BID, magnesium IV if magnesium level is below 1.9, and vitamin D PO QD if vitamin D level is below 30. Additional IV or oral magnesium and vitamin D supplementation may be administered at the investigator's discretion per standard of care. Treatment is given in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan or MRI and blood sample collection throughout the study.
Procedure: Biospecimen Collection · Dietary Supplement: Cholecalciferol · Procedure: Computed Tomography · Drug: Desloratadine · Other: Immunotherapy · Procedure: Infusion Procedure · Drug: Magnesium Sulfate · Procedure: Magnetic Resonance Imaging · Drug: Propranolol
Patients receive standard of care PD-1/PD-L1-containing immunotherapy, starting at standard of care time. Magnesium and vitamin D levels are checked with any supplementation per investigator discretion and institutional practice, without a prespecified goal level. Treatment is given in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan or MRI and blood sample collection throughout the study.
Procedure: Biospecimen Collection · Procedure: Computed Tomography · Other: Immunotherapy · Procedure: Infusion Procedure · Procedure: Magnetic Resonance Imaging
Undergo blood sample collection
Also known as: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection
Given PO
Also known as: 9,10-Secocholesta-5,7,10(19)-trien-3-ol, Calciol, Delsterol, Vitamin D3
Undergo CT scan
Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography
Given PO
Also known as: Clarinex, Sch 34117
Given standard of care immunotherapy
Also known as: Immunological, Immunological Therapy, Immunologically Directed Therapy
Immunotherapy infusion given prior to 12 PM
Also known as: Infused, Infusion
Infusion given per standard of care timing
Also known as: Infused, Infusion
Given IV
Also known as: Magnesium SO4, Magnesium Sulfate whiskers, MAGNESIUM SULFATE, UNSPECIFIED FORM
Undergo MRI
Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI
Given PO
Also known as: 1-[(1-Methylethyl)amino]-3-(1-naphthalenyloxy)-2-propanol
Change in interleukin-8 levels
The estimand for the null hypothesis will be the estimate of the difference in the average characteristics at week 12 stratified by the disease group. The null hypothesis will be tested at the 0.05 level. Tests of the null hypothesis will be conducted using the t-test. Departures from the normal distribution of the estimand will be assessed using the Shapiro-Wilk test.
Time frame: From baseline to 12 weeks
Change in interferon-gamma levels
The estimand for the null hypothesis will be the estimate of the difference in the average characteristics at week 12 stratified by the disease group. The null hypothesis will be tested at the 0.05 level. Tests of the null hypothesis will be conducted using the t-test. Departures from the normal distribution of the estimand will be assessed using the Shapiro-Wilk test.
Time frame: From baseline, up to 12 weeks
Change in effector T cells (Teff)/regulatory T cell (Treg) ratio
The estimand for the null hypothesis will be the estimate of the difference in the average characteristics at week 12 stratified by the disease group. The null hypothesis will be tested at the 0.05 level. Tests of the null hypothesis will be conducted using the t-test. Departures from the normal distribution of the estimand will be assessed using the Shapiro-Wilk test.
Time frame: From baseline, up to 12 weeks
Incidence of grade ≥ 3 treatment related adverse events (AEs)
Will report the frequency of treatment-related AEs, treatment-emergent SAEs during treatment with immunoadjuvant treatment for patients randomized to Arm A and through the first 12 protocol weeks for Arm B. For each evaluable patient, the maximum grade of each Common Terminology Criteria for Adverse Events (CTCAE) version 6 codable toxicity will be determined. For any AE event that occurs in at least one patient at grade 3 or greater, the rate of occurrence will be compared between the two randomized groups using the exact conditional test of proportions.
Time frame: From baseline, up to 12 weeks
Incidence of immune related AEs
Will report the frequency of immune related AEs during treatment for patients randomized to Arm A and through the first 12 protocol weeks for Arm B using Common Terminology Criteria for Adverse Events (CTCAE) version 6.
Time frame: From baseline, up to 12 weeks
Incidence of serious AEs
Will report the frequency of serious AEs during treatment for patients randomized to Arm A and through the first 12 protocol weeks for Arm B using Common Terminology Criteria for Adverse Events (CTCAE) version 6.
Time frame: From baseline, up to 12 weeks
This study is not yet recruiting, as verified in Sep 2026. You cannot join it, but the record below documents what was studied.
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University of Southern California