Melanoma, Prostate Cancer, Renal Cancer
Conditions
Keywords
Melanoma, Prostate Cancer, Renal Cancer
Brief summary
will scientifically evaluate whether Low Dose Naltrexone (LDN) has activity in refractory solid tumors within the context of a phase II clinical study
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.
Interventions
DRUGNaltrexone
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.
Sponsors
Brown University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Responses to Low Dose Naltrexone for Patients With Advanced Melanoma, Castrate Refractory Prostate Cancer (CRPC) or Renal Cancer Via RECIST | approximately every 3 months CT, every month physical, up to 6 months | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To Assess the Toxicity Associated With Low Dose Naltrexone for Melanoma, CRPC and Renal Cancer. | 3 months | Defined by number of patients who experienced a SAE |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Low Dose Naltrexone LDN, 5 mg/day-(1 cycle = 28 days).
Naltrexone | 7 |
| Total | 7 |
Baseline characteristics
| Characteristic | Low Dose Naltrexone |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 7 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age, Continuous | 79.4 years |
| Region of Enrollment United States | 7 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 7 / 7 |
| serious Total, serious adverse events | 0 / 7 |
Outcome results
Primary
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).
Time frame: approximately every 3 months CT, every month physical, up to 6 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Melanoma: Low Dose Naltrexone | Number of Responses to Low Dose Naltrexone for Patients With Advanced Melanoma, Castrate Refractory Prostate Cancer (CRPC) or Renal Cancer Via RECIST | progression of disease by PSA | 0 participants |
| Melanoma: Low Dose Naltrexone | Number of Responses to Low Dose Naltrexone for Patients With Advanced Melanoma, Castrate Refractory Prostate Cancer (CRPC) or Renal Cancer Via RECIST | stable disease by RECIST | 0 participants |
| Melanoma: Low Dose Naltrexone | Number of Responses to Low Dose Naltrexone for Patients With Advanced Melanoma, Castrate Refractory Prostate Cancer (CRPC) or Renal Cancer Via RECIST | progression via RECIST | 0 participants |
| Melanoma: Low Dose Naltrexone | Number of Responses to Low Dose Naltrexone for Patients With Advanced Melanoma, Castrate Refractory Prostate Cancer (CRPC) or Renal Cancer Via RECIST | progression clinical | 1 participants |
| Prostate Cancer- Low Dose Naltrexone | Number of Responses to Low Dose Naltrexone for Patients With Advanced Melanoma, Castrate Refractory Prostate Cancer (CRPC) or Renal Cancer Via RECIST | progression clinical | 0 participants |
| Prostate Cancer- Low Dose Naltrexone | Number of Responses to Low Dose Naltrexone for Patients With Advanced Melanoma, Castrate Refractory Prostate Cancer (CRPC) or Renal Cancer Via RECIST | stable disease by RECIST | 2 participants |
| Prostate Cancer- Low Dose Naltrexone | Number of Responses to Low Dose Naltrexone for Patients With Advanced Melanoma, Castrate Refractory Prostate Cancer (CRPC) or Renal Cancer Via RECIST | progression of disease by PSA | 6 participants |
| Prostate Cancer- Low Dose Naltrexone | Number of Responses to Low Dose Naltrexone for Patients With Advanced Melanoma, Castrate Refractory Prostate Cancer (CRPC) or Renal Cancer Via RECIST | progression via RECIST | 1 participants |
Secondary
To Assess the Toxicity Associated With Low Dose Naltrexone for Melanoma, CRPC and Renal Cancer.
Defined by number of patients who experienced a SAE
Time frame: 3 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Melanoma: Low Dose Naltrexone | To Assess the Toxicity Associated With Low Dose Naltrexone for Melanoma, CRPC and Renal Cancer. | 0 Participants |