Naltrexone and Propranolol Combined With Immunotherapy

ConditionAdvanced Melanoma

Trial statusRecruiting

Trial phasePhase 1

Trial typeInterventional

Biological sexAll

Age18+

SponsorSarah Weiss

About this trial

Various forms of stress can promote cancer development and growth and negatively impact the immune system's response to tumors. Beta-adrenergic and opioid receptors co-exist in many cells including immune cells and are integral components of the body's response to stress. Pre-clinical studies have demonstrated that dual blockade of these receptors can decrease tumor growth and modulate the anti-tumor immune response. This clinical trial investigates the safety and potential therapeutic benefits of combining a beta-adrenergic blocker (propranolol) and an opioid receptor antagonist (naltrexone) with immune checkpoint inhibitors in patients with advanced melanoma.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Age of 18 years or older and able to understand and sign the informed consent form.

Histologically confirmed diagnosis of unresectable stage III or stage IV melanoma.

Candidate for standard of care therapy with ipilimumab 3 mg/kg + nivolumab 1 mg/kg.

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

Disqualifiers

Presence of untreated brain metastases, unless discussed with the Principal Investigator (PI) and meet specific criteria for inclusion (treatment-naïve patients with brain metastases <10 mm, asymptomatic, without significant edema, hemorrhage, shift, or requirement for steroids or anti-seizure medications, and not in eloquent areas). These patients may potentially forego initial local treatment of the brain metastases and have them reassessed after consultation with the Neurosurgery and Radiation Oncology teams.

Use of corticosteroids to control immune-related adverse events at enrollment. Participants who previously required corticosteroids for symptom control must be off steroids for at least two weeks. Low-dose steroid use (=10 mg of prednisone or equivalent) as corticosteroid replacement therapy for primary or secondary adrenal insufficiency is allowed.

Failure to recover (i.e., Grade 1 or at baseline) from adverse events due to prior treatment.

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

Trial design

Design model

Sequential

Treatments tested in this trial

Propranolol
Drug
Propranolol will be administered to patients in all cohorts.
Naltrexone
Drug
Naltrexone will be administered to patients in cohorts 2, 3, and 4.

Treatment groups

12 Participants

are divided into 4 treatment groups

Group A: Cohort 1 - PropranololExperimental treatment 1 intervention

Group B: Cohort 2 - Propranolol + Naltrexone 4.5 mgExperimental treatment 2 interventions

Group C: Cohort 3 - Propranolol + Naltrexone 9 mgExperimental treatment 2 interventions

Group D: Cohort 4 - Propranolol + Naltrexone 25 mgExperimental treatment 2 interventions

Trial outcomes

Primary outcomes

Safety as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5.0

Time frame

initial 28 days of treatment and then for up to 2 years

Dose-limiting toxicity of naltrexone in combination with propranolol and ipilimumab plus nivolumab

Time frame

initial 28 days of treatment

Recommended phase 2 dose of naltrexone in combination with propranolol and ipilimumab plus nivolumab

Time frame