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.
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
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
Parallel
Biospecimen Collection
Procedure/SurgeryUndergo blood sample collection
Cholecalciferol
Dietary supplementGiven PO
Computed Tomography
Procedure/SurgeryUndergo CT scan
Desloratadine
DrugGiven PO
Immunotherapy
Other interventionGiven standard of care immunotherapy
Infusion Procedure
Procedure/SurgeryImmunotherapy infusion given prior to 12 PM
Infusion Procedure
Procedure/SurgeryInfusion given per standard of care timing
Magnesium Sulfate
DrugGiven IV
Magnetic Resonance Imaging
Procedure/SurgeryUndergo MRI
Propranolol
DrugGiven PO
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.
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.
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.
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.
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.
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.
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University of Southern California
Lead sponsor
National Cancer Institute (NCI)
Collaborator
This trial is not recruiting at the moment. You can still explore other options:
