Advanced Hepatocellular CarcinomaPhase 2NCT07836712
Multiple Adjunct Therapies to Improve Immunotherapy Treatment in Patients With Locally Advanced or Metastatic Melanoma or Advanced Hepatocellular Cancer
A Phase 2 study testing Biospecimen Collection, Cholecalciferol and Computed Tomography in people with Advanced Hepatocellular Carcinoma and Advanced Melanoma, run by University of Southern California at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Hepatocellular Carcinoma, Advanced Melanoma, Locally Advanced Melanoma
- What is being tested?
- Biospecimen Collection, Cholecalciferol and Computed Tomography
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 46 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Nov 2026to 1 Nov 2028
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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:
- Oral, intravaginal, or transdermal combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation
- Oral, injectable, or implantable progestogen-only hormonal contraception associated with inhibition of ovulation
- Intrauterine device
- Intrauterine hormone-releasing system
- Bilateral tubal occlusion
- Vasectomized partner (provided that partner is the sole sexual partner of the female of reproductive potential and that the vasectomized partner has received medical assessment of the surgical success)
- 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
- Males who have female partners of childbearing potential must agree to use a highly effective method of contraception from the start of therapy through 90 days after the completion of therapy
- Ability to understand and the willingness to sign a written informed consent
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033
Diana Hanna, 323-865-3000
Diana Hanna
About this study
Official title: ADD-IT1: A Randomized Study of Adjuncts to Immunotherapy in Patients With Advanced Cancers
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.
Read the detailed description
PRIMARY OBJECTIVE:
- 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:
- 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:
- 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.
- Conditions
- Advanced Hepatocellular Carcinoma, Advanced Melanoma, Locally Advanced Melanoma, Metastatic Melanoma, Stage III Hepatocellular Carcinoma AJCC v8, Stage IV Hepatocellular Carcinoma AJCC v8
- Being tested
- Biospecimen Collection, Cholecalciferol, Computed Tomography, Desloratadine, Immunotherapy
- Medical subject headings
- Melanoma, Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection
Undergo blood sample collection
CholecalciferolDietary supplement
Also called 9,10-Secocholesta-5,7,10(19)-trien-3-ol, Calciol, Delsterol, Vitamin D3
Given PO
Computed TomographyProcedure or surgery
Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography
Undergo CT scan
DesloratadineDrug
Also called Clarinex, Sch 34117
Given PO
ImmunotherapyOther
Also called Immunological, Immunological Therapy, Immunologically Directed Therapy
Given standard of care immunotherapy
Infusion ProcedureProcedure or surgery
Also called Infused, Infusion
Immunotherapy infusion given prior to 12 PM
Infusion ProcedureProcedure or surgery
Also called Infused, Infusion
Infusion given per standard of care timing
Magnesium SulfateDrug
Also called Magnesium SO4, Magnesium Sulfate whiskers, MAGNESIUM SULFATE, UNSPECIFIED FORM
Given IV
Magnetic Resonance ImagingProcedure or surgery
Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan
Undergo MRI
PropranololDrug
Also called 1-[(1-Methylethyl)amino]-3-(1-naphthalenyloxy)-2-propanol
Given PO
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Procedure: Biospecimen Collection; Procedure: Computed Tomography; Other: Immunotherapy; Procedure: Infusion Procedure; Procedure: Magnetic Resonance Imaging |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: From baseline, up to 12 weeks
Secondary outcomes (3)
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.
Measured: 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.
Measured: 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.
Measured: From baseline, up to 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Sep 2026
- Study start1 Nov 2026 (estimated)
- Primary completion1 Nov 2027 (estimated)
- Study completion1 Nov 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Hepatocellular CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 46 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Southern California
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Diana Hanna, Principal investigator, University of Southern California
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07836712
- Sponsor's protocol ID
- 0C-26-9
- Other IDs
- NCI-2026-06680, 0C-26-9, P30CA014089
- Status last verified
- Sep 2026
- First submitted
- 17 Sep 2026
- Last updated
- 23 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No