What side effects are associated with this type of intervention?

Common treatments for melanoma include immune checkpoint inhibitors, targeted therapies, and chemotherapy. Immune checkpoint inhibitors, such as nivolumab and pembrolizumab, can cause side effects like fatigue, rash, diarrhea, and immune-related adverse events affecting organs like the liver and lungs. Targeted therapies, such as BRAF and MEK inhibitors, may lead to side effects including fever, fatigue, joint pain, and skin issues. Chemotherapy can cause nausea, vomiting, hair loss, and increased risk of infection. For treatments similar to Propranolol and Naltrexone, beta-adrenergic blockers can cause fatigue, dizziness, and cold extremities, while opioid receptor antagonists may lead to gastrointestinal issues and, in some cases, withdrawal symptoms.

What prior FDA approvals exist?

The FDA has approved various treatments for melanoma, particularly targeting specific genetic mutations and pathways. For instance, the combination of dabrafenib and trametinib has been approved for patients with BRAF V600-mutant melanoma. These drugs target the BRAF mutation and the MEK pathway, respectively. While the trial involving Propranolol and Naltrexone is exploring a novel approach by combining a beta-adrenergic blocker and an opioid receptor antagonist with immune checkpoint inhibitors, there is no direct mention of prior FDA approvals for this specific combination in the provided context.

What other types of research exist?

Promising novel alternatives for melanoma treatment in 2024 include immune checkpoint inhibitors such as pembrolizumab and nivolumab, which target PD-1, and combination therapies like nivolumab with ipilimumab (CTLA-4 inhibitor). Additionally, targeted therapies for specific mutations, such as BRAF inhibitors (dabrafenib) combined with MEK inhibitors (trametinib), are also showing significant efficacy.

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Naltrexone + Propranolol Combined With Immunotherapy for Melanoma

Phase 1

Recruiting

Led By Sarah Weiss, MD

Research Sponsored by Sarah Weiss

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Histologically confirmed diagnosis of unresectable stage III or stage IV melanoma

Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

Must not have

Concurrent, active malignancies in addition to those being studied, except for cutaneous squamous cell carcinoma or basal cell carcinoma

History of grade 3-4 neurologic or cardiac toxicity or life-threatening liver toxicity poorly responsive to steroids with prior anti-PD-1 therapy

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a new treatment for patients with advanced melanoma. The treatment combines drugs that block stress signals with drugs that help the immune system fight cancer. Researchers want to see if this combination is safe and effective.

Who is the study for?

Adults with advanced melanoma, either treatment-naïve or previously treated, can join this trial. They must have measurable cancer lesions and normal organ function. Women of childbearing age should use effective contraception or abstain from sex for six months post-treatment; men also need to agree to contraception use. Participants cannot have other active cancers, untreated brain metastases, severe past reactions to anti-PD-1 therapy, certain infections like hepatitis B/C, or be on steroids at enrollment.

What is being tested?

The trial tests the combination of propranolol (a beta-blocker) and naltrexone (an opioid blocker) with standard immunotherapy in patients with melanoma. It aims to see if stress receptor blockade enhances immune response against tumors. Patients will receive these medications alongside immune checkpoint inhibitors ipilimumab and nivolumab.

What are the potential side effects?

Potential side effects include low blood pressure or slowed heart rate due to propranolol; nausea or headaches from naltrexone; plus typical immunotherapy side effects such as fatigue, skin reactions, inflammation in organs like lungs (pneumonitis), liver issues, hormonal changes and potential autoimmune responses.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My melanoma is at an advanced stage and cannot be surgically removed.

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I am fully active or have some restrictions but can still care for myself.

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I am eligible for treatment with ipilimumab and nivolumab.

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My blood tests show normal organ function.

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I am a male and agree to use contraception for six months after my last treatment dose.

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I can provide a biopsy from my cancer for the study, or discuss alternatives if not possible.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have no other cancers except for skin cancer.

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I've had severe nerve, heart, or liver side effects from previous anti-PD-1 therapy.

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My cancer has spread to the lining of my brain and spinal cord.

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I have lung inflammation that is not caused by an infection.

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I have received a live vaccine recently.

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I have an acute or chronic Hepatitis B or C infection.

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I still have side effects from previous treatments that haven't gone away.

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I have an autoimmune disease but haven't needed strong medication for it in the last year.

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I do not have severe asthma, heart issues, uncontrolled diabetes or depression, and I'm not allergic to propranolol.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

4Treatment groups

Experimental Treatment

Group I: Cohort 4 - Propranolol + Naltrexone 25 mgExperimental Treatment2 Interventions

Patients will receive intravenous ipilimumab 3 mg/kg + nivolumab 1 mg/kg every 21 days for up to 4 cycles followed by intravenous nivolumab monotherapy 480 mg every 28 days. Propranolol will be administered as 30 mg orally twice a day, continuously. Naltrexone will be administered as 25 mg orally once a day, continuously.

Group II: Cohort 3 - Propranolol + Naltrexone 9 mgExperimental Treatment2 Interventions

Group III: Cohort 2 - Propranolol + Naltrexone 4.5 mgExperimental Treatment2 Interventions

Group IV: Cohort 1 - PropranololExperimental Treatment1 Intervention

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Naltrexone

2005

Completed Phase 4

~2420

Propranolol

2010

Completed Phase 4

~1290

0 / 15Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Propranolol, a beta-adrenergic blocker, works by inhibiting the effects of stress hormones like adrenaline, which can promote tumor growth and metastasis. Naltrexone, an opioid receptor antagonist, blocks opioid receptors that can modulate immune responses and potentially enhance anti-tumor immunity. These mechanisms are significant for melanoma patients because they target the stress and immune pathways that can influence cancer progression. By combining these drugs with immune checkpoint inhibitors, the treatment aims to reduce tumor growth and improve the body's immune response to melanoma, offering a potentially more effective therapeutic strategy.