- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05968690
Naltrexone and Propranolol Combined With Immunotherapy
A Phase I Study to Evaluate the Safety of Naltrexone and Propranolol in Combination With Standard of Care Ipilimumab and Nivolumab in Patients With Advanced Melanoma
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Estimated)
Phase
- Phase 1
Contacts and Locations
Study Contact
- Name: Sarah Weiss, MD
- Phone Number: 732-235-2465
- Email: saweiss@cinj.rutgers.edu
Study Locations
-
-
New Jersey
-
New Brunswick, New Jersey, United States, 08903
- Recruiting
- Rutgers Cancer Institute of New Jersey
-
Contact:
- Sarah Weiss, MD
- Phone Number: 732-235-2465
- Email: saweiss@cinj.rutgers.edu
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- 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.
- Treatment-naïve or has received any number of prior lines of therapy. Prior targeted therapy is allowed, but small molecule inhibitors must be discontinued within two weeks before starting the study.
- Life expectancy of at least 6 months.
- Presence of at least one accessible site of disease to provide an on-study biopsy for tumor tissue. The biopsy may be waived after discussion with the Principal Investigator (PI) if it is deemed unfeasible. The site may be a target lesion as long as it will not be rendered unmeasurable by the biopsy procedure.
- Willingness to undergo tumor biopsy (if archival tumor is not available) prior to initiation of therapy and while on the study.
- Willingness to provide an archival specimen block, if available, for research purposes.
Normal organ function, defined as:
- Absolute neutrophil count (ANC) >1500/mcL
- Platelets >100,000/mcL
- Hemoglobin (Hb) >9 g/dL
- Albumin >2.5 mg/dL
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <2.5 times the upper limit of normal (ULN)
- Serum total bilirubin <1.5 times ULN or direct bilirubin < ULN for subjects with total bilirubin levels >1.5 times ULN.
- Female participants of childbearing potential should have a negative serum pregnancy test within 72 hours prior to receiving the first dose of study medication.
- Female participants of childbearing potential should be willing to use a highly effective form of contraception (hormonal or intrauterine device) along with a condom in their male partner, or be surgically sterile, or abstain from heterosexual activity for a period of at least six months after the last dose of study medication.
- Male participants should agree to use an adequate method of contraception starting with the first dose of study therapy through at least six months after the last dose of study drug.
- Participants must have at least one measurable lesion at baseline by computed tomography (CT) or magnetic resonance imaging (MRI) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. Tumor sites situated in a previously irradiated area or in an area subjected to other loco-regional therapy are not considered measurable unless there has been demonstrated progression in the lesion.
- Prior focal radiotherapy is allowed.
Exclusion Criteria:
- 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.
- Presence of leptomeningeal disease.
- Active autoimmune disease unrelated to the use of immune checkpoint inhibitors that has required systemic treatment in the past year (e.g., use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
Contraindications to the use of propranolol, including:
- Cardiogenic shock.
- Sinus bradycardia greater than first-degree block.
- Severe bronchial asthma.
- Known hypersensitivity to propranolol.
- Requirement for current use of an alternative beta-blocker.
- Uncontrolled diabetes.
- Uncontrolled depression.
- Unstable angina or myocardial infarction within 3 months of Day 1 Cycle 1.
For enrollment into Cohort 2-4 ONLY: Contraindications to the use of naltrexone, including:
- Participants currently receiving opioid analgesics or anticipated to require opioid analgesics in the near future.
- Participants currently dependent on opioids, including those currently maintained on opiate agonists (e.g., methadone) or partial agonists (e.g., buprenorphine).
- Participants in acute opioid withdrawal.
- Individuals with a history of sensitivity to naltrexone.
- Pregnancy or breastfeeding. If a woman becomes pregnant or suspects she is pregnant while participating in this study, she should inform her treating physician immediately. Breastfeeding must be discontinued if the mother is enrolled in this trial due to the potential risk for adverse events in nursing infants.
- Receipt of any other investigational agents or participation in a study of an investigational agent or use of an investigational device within four weeks of the first dose of treatment.
- Concurrent condition (including medical illness, active infection requiring treatment with intravenous antibiotics, or presence of laboratory abnormalities) or history of a prior condition that places the patient at unacceptable risk if treated with the study drug or confounds the ability to interpret data from the study.
- Concurrent, active malignancies in addition to those being studied, except for cutaneous squamous cell carcinoma or basal cell carcinoma.
- Active (non-infectious) pneumonitis.
- Hepatitis B (HBV) or Hepatitis C (HCV) acute or chronic infection.
- Receipt of a live vaccine
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Cohort 1 - Propranolol
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. |
Propranolol will be administered to patients in all cohorts.
|
Experimental: Cohort 2 - Propranolol + Naltrexone 4.5 mg
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 4.5 mg orally once a day, continuously. |
Propranolol will be administered to patients in all cohorts.
Naltrexone will be administered to patients in cohorts 2, 3, and 4.
|
Experimental: Cohort 3 - Propranolol + Naltrexone 9 mg
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 9 mg orally once a day, continuously. |
Propranolol will be administered to patients in all cohorts.
Naltrexone will be administered to patients in cohorts 2, 3, and 4.
|
Experimental: Cohort 4 - Propranolol + Naltrexone 25 mg
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. |
Propranolol will be administered to patients in all cohorts.
Naltrexone will be administered to patients in cohorts 2, 3, and 4.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
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
|
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
|
initial 28 days of treatment
|
Recommended phase 2 dose of naltrexone in combination with propranolol and ipilimumab plus nivolumab
Time Frame: up to 2 years from start of treatment
|
up to 2 years from start of treatment
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Time Frame: up to 2 years from start of treatment
|
up to 2 years from start of treatment
|
Progression-Free Survival (PFS)
Time Frame: up to 2 years from start of treatment
|
up to 2 years from start of treatment
|
Overall Survival (OS)
Time Frame: up to 2 years from start of treatment
|
up to 2 years from start of treatment
|
Other Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Exploratory objectives are to assess the impact of propranolol + naltrexone on the anti-tumor immune response through correlative biomarker studies performed on tumor and blood.
Time Frame: up to 2 years from start of treatment
|
up to 2 years from start of treatment
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Sarah Weiss, MD, Rutgers Cancer Institute of New Jersey
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Neuroendocrine Tumors
- Nevi and Melanomas
- Melanoma
- Physiological Effects of Drugs
- Adrenergic beta-Antagonists
- Adrenergic Antagonists
- Adrenergic Agents
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Anti-Arrhythmia Agents
- Antihypertensive Agents
- Vasodilator Agents
- Peripheral Nervous System Agents
- Sensory System Agents
- Narcotic Antagonists
- Alcohol Deterrents
- Propranolol
- Naltrexone
Other Study ID Numbers
- 092302
- Pro2023001214 (Other Identifier: Rutgers, The State University of New Jersey)
- NCI-2023-06872 (Other Identifier: NCI CTRP (Clinical Trial Reporting Program))
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Advanced Melanoma
-
Vanderbilt-Ingram Cancer CenterNational Cancer Institute (NCI); National Comprehensive Cancer NetworkTerminatedRecurrent Melanoma | Stage IIIA Melanoma | Stage IIIB Melanoma | Stage IIIC Melanoma | Stage IIB Melanoma (Locally Advanced) | Stage IIC Melanoma (Locally Advanced) | Stage IV Melanoma (Limited, Resectable)United States
-
BiocadRecruitingMelanoma | Melanoma (Skin) | Melanoma Stage IV | Melanoma Stage III | Melanoma Metastatic | Melanoma Unresectable | Melanoma AdvancedIndia, Russian Federation, Belarus
-
Regeneron PharmaceuticalsBristol-Myers SquibbCompletedMelanoma | Metastatic Melanoma | Unresectable Melanoma | Advanced MelanomaUnited States
-
Regeneron PharmaceuticalsBristol-Myers SquibbActive, not recruitingMelanoma | Metastatic Melanoma | Unresectable Melanoma | Advanced MelanomaUnited States
-
MorphotekTerminatedMelanoma | Metastatic Melanoma | Advanced Melanoma | Malignant Metastatic MelanomaUnited States
-
Millennium Pharmaceuticals, Inc.CompletedAdvanced Metastatic Melanoma | Advanced Non-hematologic MalignanciesUnited States
-
University of Colorado, DenverMerck Sharp & Dohme LLCActive, not recruitingStage IV Melanoma | Advanced Melanoma | Stage III MelanomaUnited States
-
Azienda Ospedaliera di PerugiaNot yet recruitingAdvanced Melanoma | Early MelanomaItaly, Sweden, France, Germany, Netherlands, Poland, Spain
-
Cancer Trials IrelandCompletedMetastatic Melanoma | Advanced MelanomaIreland
-
Shanghai Junshi Bioscience Co., Ltd.UnknownMetastatic Melanoma | Advanced MelanomaChina
Clinical Trials on Propranolol
-
University of UtahTerminated
-
University Hospital, GenevaSuspendedStage IB Skin Melanoma | Stages III Skin Melanoma | Stages II Skin MelanomaSwitzerland
-
Mela, Mansfield, M.D.UnknownPosttraumatic Stress Disorder | Traumatic MemoryCanada
-
Academisch Medisch Centrum - Universiteit van Amsterdam...Completed
-
Govind Ballabh Pant HospitalUnknownHepatic EncephalopathyIndia
-
Douglas Mental Health University InstituteInstitut de Recherche Robert-Sauvé en Santé et en Sécurité du TravailRecruitingTrauma and Stressor Related Disorders | Post-traumatic Stress Disorders | Adjustment Disorders | Acute Stress DisorderCanada
-
Taipei Veterans General Hospital, TaiwanUnknownCirrhosis | Acute Kidney Injury | Esophageal VaricesTaiwan
-
Vanderbilt UniversityCompleted
-
Kent State UniversityAkron Children's Hospital; Ohio Board of RegentsCompletedPosttraumatic Stress Disorders
-
Assiut UniversityUnknown