Multiple Adjunct Therapies to Improve Immunotherapy Treatment in Patients With Locally Advanced or Metastatic Melanoma or Advanced Hepatocellular Cancer

NCT07836712 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: 0C-26-9NCI-2026-06680P30CA014089
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Advanced Melanoma; Locally Advanced Melanoma; Metastatic Melanoma; Stage III Hepatocellular Carcinoma AJCC v8; Stage IV Hepatocellular Carcinoma AJCC v8; Advanced Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (3)

• 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.

  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.

  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.

  From baseline, up to 12 weeks

Secondary Outcomes (3)

• Incidence of grade ≥ 3 treatment related adverse events (AEs)

  From baseline, up to 12 weeks

• Incidence of immune related AEs

  From baseline, up to 12 weeks

• Incidence of serious AEs

  From baseline, up to 12 weeks

Study Arms (2)

Arm A (Adjunct interventions)

EXPERIMENTAL

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

Arm B (Standard interventions)

ACTIVE COMPARATOR

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

Interventions

Cholecalciferol DIETARY_SUPPLEMENT

Given PO

Also known as: 9,10-Secocholesta-5,7,10(19)-trien-3-ol, Calciol, Delsterol, Vitamin D3

Arm A (Adjunct interventions)

Computed Tomography PROCEDURE

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

Arm A (Adjunct interventions); Arm B (Standard interventions)

Desloratadine DRUG

Given PO

Also known as: Clarinex, Sch 34117

Arm A (Adjunct interventions)

Immunotherapy OTHER

Given standard of care immunotherapy

Also known as: Immunological, Immunological Therapy, Immunologically Directed Therapy

Arm A (Adjunct interventions); Arm B (Standard interventions)

Magnesium Sulfate DRUG

Given IV

Also known as: Magnesium SO4, Magnesium Sulfate whiskers, MAGNESIUM SULFATE, UNSPECIFIED FORM

Arm A (Adjunct interventions)

Magnetic Resonance Imaging PROCEDURE

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

Arm A (Adjunct interventions); Arm B (Standard interventions)

Propranolol DRUG

Given PO

Also known as: 1-[(1-Methylethyl)amino]-3-(1-naphthalenyloxy)-2-propanol

Arm A (Adjunct interventions)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

Arm A (Adjunct interventions); Arm B (Standard interventions)

Infusion Procedure PROCEDURE

Immunotherapy infusion given prior to 12 PM

Also known as: Infused, Infusion

Arm A (Adjunct interventions)

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed locally advanced or metastatic melanoma or advanced hepatocellular cancer (HCC); histologic/cytologic confirmation not required for HCC
• Eligible and planned to begin therapy with PD1/PDL-1 inhibitors as standard of care first-line therapy, either as monotherapy or in combination with other approved immune checkpoint inhibitors or bevacizumab
• Age ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Absolute neutrophil count ≥ 1,000/mcl
• Hemoglobin ≥ 8.0 g/dL
• Platelets ≥ 75,000/mcl
• Total bilirubin ≤ 1.5 × upper limit of normal (ULN) or ≤ 3 × ULN in Gilbert's syndrome
• Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\])/ alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) ≤ 2.5 × ULN for patients without liver metastasis ≤ 5 × ULN for patients with liver metastasis
• Creatinine clearance \> 30 mL/min per Cockcroft-Gault
• Females of childbearing potential must agree to sexual abstinence (defined below) or be willing to use a highly effective method of contraception from the start of therapy through 90 days after the completion of therapy.
• Non-childbearing potential is defined as:
• Postmenopausal, defined as no menses for 12 months without an alternative medical cause. A high follicle-stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.
• Surgically sterile. Surgical sterilization methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy.
• Acceptable highly effective birth control methods include:

You may not qualify if:

• Prior systemic anticancer therapy for locally advanced or metastatic disease. Therapy in the neoadjuvant or adjuvant setting is allowed if the last dose of neo/adjuvant therapy is at least 6 months prior to first dose of study treatment
• 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).
• Note: Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is allowed
• History of grade ≥ 3 immune-related adverse event(s) associated with prior immunotherapy, unless these events did not require hospitalization, were manageable with medical therapy, and adequately resolved within 14 days
• Medical requirement for beta blockers or histamine 1 (H1) blockers
• Has active central nervous system (CNS) metastases and/or any history of leptomeningeal disease
• Note: Patients with previously treated brain metastases may participate provided they are radiologically stable (i.e. no evidence of progression for ≥ 4 weeks by repeat imaging performed during study screening), clinically stable, and not requiring steroid treatment within 14 days prior to first dose of study treatment
• Has received a live vaccine administered within 28 days of planned treatment start or while participating in the study
• Patients must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants
• History of or current condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate
• Contraindications to the use of beta-blockers, including but not limited to unstable angina pectoris, uncontrolled heart failure (Grade III or IV), hypotension (systolic blood pressure \< 100 mmHg), bradycardia
• Patients must not be receiving other concomitant biologic therapy, hormonal therapy, chemotherapy, other anti-cancer therapy or any other investigational agents while on this protocol

Sponsors & Collaborators

• University of Southern California: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

MeSH Terms

Conditions

Melanoma; Carcinoma, Hepatocellular

Interventions

Specimen Handling; Cholecalciferol; desloratadine; Immunotherapy; Adjuvants, Immunologic; Magnesium Sulfate; Magnetic Resonance Spectroscopy; Propranolol

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Liver Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Lipids; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Factors; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Magnesium Compounds; Inorganic Chemicals; Sulfates; Sulfuric Acids; Sulfur Acids; Sulfur Compounds; Spectrum Analysis; Chemistry Techniques, Analytical; Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

• Diana Hanna

  University of Southern California

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Patients will be randomized in a 1:1 ratio to Arm A (Adjuncts/Early ICI Infusion) or Arm B (No Adjuncts/ SOC ICI Infusion).
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 17, 2026
• First Posted: September 23, 2026
• Study Start (Estimated): November 1, 2026
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): November 1, 2028
• Last Updated: September 23, 2026

Record last verified: 2026-09

Locations

US (1)