Low Dose Naltrexone for Metastatic Melanoma, Castrate Resistant Prostate Cancer and Renal Cancer

Low Dose Naltrexone for Metastatic Melanoma, Castrate Resistant Prostate Cancer and Renal Cancer: A Phase II Brown University Oncology Group Research Project

will scientifically evaluate whether Low Dose Naltrexone (LDN) has activity in refractory solid tumors within the context of a phase II clinical study

Study Overview

• Status: Terminated
• Conditions: Melanoma; Prostate Cancer; Renal Cancer
• Intervention / Treatment: Drug: Naltrexone

Detailed Description

Three types of solid tumors will be studied in this protocol: Melanoma, castrate resistant prostate cancer and kidney cancer. Systemic chemotherapy may weaken the immune system reducing the potential for response to LDN. Therefore, patients must either have not had previous chemotherapy or patients must not have received more than 1 prior chemotherapy regimen which must have been completed at least 6 months prior to LDN. Systemic chemotherapy has at best modest activity in melanoma, CRPC and renal cancer.

• Melanoma will be evaluated since the responding patient at the Miriam Hospital had melanoma. Immunomodulatory agents such as ipilimumab have already demonstrated a survival advantage in melanoma.
• Castrate Resistant Prostate Cancer (CRPC): It is common in CRPC for patients to have rising PSA after failure of androgen deprivation. These patients may be asymptomatic or minimally symptomatic and there is reluctance to initiate treatment with systemic chemotherapy with standard docetaxel since this agent has substantial toxicity and will impair quality of life. Waiting until symptomatic disease progression in patients with CRPC and rising PSA is a commonly utilized strategy. These patients are excellent candidates for a treatment with minimal toxicity such as LDA. The immunomodulatory agent Sipuleucel also improves survival in prostate cancer suggesting that an agent such as LDN could also be helpful.
• Renal cancer will also be studied since this is a disease that has activity with immunomodulants such as IL-2 and interferon. Targeted therapies are generally used for renal cancer. Chemotherapy has minimal activity so most patients are chemotherapy-naive.

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Rhode Island
    • Providence, Rhode Island, United States, 02912
      • Miriam Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Conditions for Patient Eligibility

Each patient must meet all of the following inclusion criteria to be enrolled in the study:

• Histologically or pathologically confirmed melanoma, renal cancer or prostate cancer.
• Patients with melanoma or renal cancer must have metastatic disease.
• Patients with melanoma or renal cancer must have radiographically measurable advanced disease. Patients with measurable cutaneous lesions are also evaluable patients with prostate cancer must be castrate refractory and must have radiographically assessable metastatic disease or must have rising PSA on two sequential measurements.
• No prior chemotherapy, or have not received cytotoxic chemotherapy within the 6 months prior to entry..
• No radiation for 3 weeks prior to beginning Naltrexone
• No requirement for opioid analgesics orNo use of opioid analgesics for at least 10 days.
• Absolute neutrophil count ≥ 1,000/uL, platelet ≥ 75,000/uL.
• Total bilirubin ≤ 1.5x upper institutional limit (ULN) and AST or ALT ≤ 3x ULN;
• No prior history of hepatic failure, cirrhosis or hepatic encephalopathy
• ECOG performance status 0 to 2.
• Creatinine < 1.5 x ULN
• Life expectancy of at least 8 weeks.
• Age ≥ 18 years
• Women of childbearing potential must have a negative pregnancy test.
• Men and women of childbearing potential must be willing to consent to using effective contraception while on treatment and for at least 1 months thereafter.
• Voluntary written informed consent.
• Conditions for Patient Ineligibility Patients meeting any of the following exclusion criteria are not to be enrolled in the study.
• Must not have uncontrolled severe, intercurrent illness.
• Women who are breast-feeding.
• Patients who have undergone major surgery or radiotherapy within the last 3 weeks.
• Patients on concurrent anticancer therapy.
• Patients with known, untreated brain metastasis
• Co-medication that may interfere with study results; e.g opioids
• Known hypersensitivity to any component of naltrexone
• Current or prior alcohol dependence
• Patients who could benefit from conventional therapy are not eligible.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Low Dose Naltrexone; LDN, 5 mg/day-(1 cycle = 28 days).

Drug: Naltrexone; 4.1 Low Dose Naltrexone (LDN) LDN, 5 mg/day, at approximately 9pm, on an empty stomach, until disease progression, unacceptable toxicity, need for initiation of narcotic analgesia, or removal from protocol treatment according to section 12.0. (1 cycle = 28 days). LDN, 5mg/ml, will be prepared by the Lifespan hospital pharmacy for patient use for this study.; Other Names: Revia and Vivitrol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Responses to Low Dose Naltrexone for Patients With Advanced Melanoma, Castrate Refractory Prostate Cancer (CRPC) or Renal Cancer Via RECIST	Response will be assessed via RECIST 1.1 criteria utilizing interval CT scans and physical exam after every 3 cycles of treatment (i.e. every 12 weeks).	approximately every 3 months CT, every month physical, up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To Assess the Toxicity Associated With Low Dose Naltrexone for Melanoma, CRPC and Renal Cancer.	Defined by number of patients who experienced a SAE	3 months

Collaborators and Investigators

• Sponsor: Brown University
• Investigators: Study Director: Howard Safran, MD, Brown University

Study record dates

Study Major Dates

• Study Start: November 1, 2012
• Primary Completion (Actual): October 1, 2013
• Study Completion (Actual): October 1, 2013

Study Registration Dates

• First Submitted: July 24, 2012
• First Submitted That Met QC Criteria: July 24, 2012
• First Posted (Estimate): July 26, 2012

Study Record Updates

• Last Update Posted (Actual): March 4, 2022
• Last Update Submitted That Met QC Criteria: February 23, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: Prostate Cancer; Melanoma; Renal Cancer
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Male; Prostatic Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Kidney Neoplasms; Carcinoma, Renal Cell; Prostatic Neoplasms; Melanoma; Physiological Effects of Drugs; Peripheral Nervous System Agents; Sensory System Agents; Narcotic Antagonists; Alcohol Deterrents; Naltrexone
• Other Study ID Numbers: BrUOG 275