- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00256230
Disulfiram in Patients With Metastatic Melanoma
Evaluation of Disulfiram in Patients With Metastatic Melanoma and at Least One Prior Systemic Therapy, Phase I/II
Melanoma remains a malignancy that is largely resistant to chemotherapy. Metastatic disease responds poorly to the treatments used today with only 2 out of 30 drugs tested, DTIC and nitrosoureas, showing response rates greater than 10%, and complete responses are rare. DTIC-based regimen has been recognized as a standard chemotherapy for advanced melanoma, and temozolomide demonstrated efficacy equal to that of DTIC and is an oral alternative agent that also crosses the blood brain barrier. Randomized phase III trials have shown no survival benefit of adding other agents (cisplatin, BCNU, and tamoxifen). Biochemotherapy is being developed extensively with moderate improvement in the responsive rate (approximately 50%) and is under evaluation in randomized trial to identify whether there is survival benefit to this strategy, compared with chemotherapy alone. Recently, a randomized phase III study comparing chemotherapy (cisplatin, dacarbazine, and tamoxifen) with biochemotherapy (the same chemotherapy regimen plus high-dose IL-2 and interferon alfa) have shown 44% response rate for biochemotherapy vs. 27% for chemotherapy. However, the tendency toward an increased response rate in patients who received biochemotherapy did not translate into an increase in overall survival, and there was, in fact, a trend for a survival advantage in patients receiving chemotherapy alone (median survival: 10.7 vs 15.8 months). New agents (or combinations) need to be developed for this refractory malignancy.
The purpose of this study is to determine the response rate and evaluate the toxicity of disulfiram (DSF) in the treatment of Stage IV melanoma.
The advantages of using DSF in this phase I/II trial are the following:
- DSF has been used as a drug for many years for the treatment of alcoholism. Its mechanism, pharmacokinetics, toxicity/tolerable dose are well known, and this drug is relatively non-toxic by itself at therapeutic dose. Doses of greater than 3000mg/m2 can cause reversible confusion.
- DSF can be taken orally; therefore, it is convenient to administer.
- DSF can penetrate the blood-brain barrier (unlike dacarbazine and many other chemotherapy agents); therefore, it might have an active effect on CNS metastasis.
This study is designed to include women and minorities, but is not designed to measure differences of intervention effect.
Study Overview
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
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California
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Orange, California, United States, 92868
- Chao Family Comprehensive Cancer Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Subjects must be between the ages of 18 and 80.
- Patient must have pathologically proven and surgically incurable malignant melanoma, which is Stage IV.
- Patient must have bidimensionally measurable disease. All measurable lesions must be assessed (by physical examination, CT scan, radionuclide scan or plain X-ray) within 28 days prior to registration. Non-measurable sites must be assessed within 42 days prior to registration. The patient's disease status must be completely assessed and reported.
- All patients must undergo a CT of abdomen and chest within 28 days prior to registration.
- All patients must undergo either a CT or MRI of the brain within 28 days of registration. Patients with or without brain metastasis are both recruited for this protocol.
- Patients must have received at least one prior systemic therapy (chemotherapy, biologic/immunotherapy, or a combination regimen) for metastatic disease. Prior systemic therapy must have been completed at least 28 days before registration.
- Patients may have received prior biologic or immunotherapy given in an adjuvant fashion. Prior adjuvant therapy must have been completed at least 28 days prior to registration
- Patients may have received prior radiation therapy. If all known sites of disease have been previously radiated, there must be objective evidence of progression for the patient to be eligible. Radiation therapy must have been completed at least 28 days before registration.
- Patients may have received prior surgery. Prior surgery must have been completed at least 28 days before registration.
- Performance status must be 0-2 according to Zubrod Criteria.
- If day 28 or 42 falls on a weekend or holiday, the limit may be extended to the next working day.
- Patients must be informed of the investigational nature of this study and sign and give written informed consent in accordance with institutional and federal guidelines.
Exclusion Criteria:
- Patients with severe myocardial disease or coronary occlusion, psychoses, and hypersensitivity to disulfiram or other thiuram derivatives used in pesticides and rubber vulcanization are excluded from the study.
- Patients who cannot abstain from alcohol intake during the entire duration of this protocol are not qualified for this study.
- Patients requiring ongoing therapy with other investigational drugs are excluded.
- Pregnant or nursing women are not eligible to participate in this trial because the safe use of this drug in pregnancy has not been established.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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EXPERIMENTAL: Disulfiram
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DSF pills at 250 mg will be given orally, two times a day.
If this dose is tolerated, the dose will be escalated until the maximum tolerated dose is reached.
Treatment will continue every day for 3 months or longer unless the disease gets worse, the side effects are too dangerous for the subject, or the subject decides to discontinue treatment.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Determine response rate
Time Frame: Every 8 weeks during therapy
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Complete response (CR)-Complete disappearance of all measurable and evaluable disease.
No disease related symptoms.
No evidence of non-evaluable disease, including normalization of markers and other abnormal lab values.
Partial response (PR)-Applies only to patients with at least one measurable lesion.
Greater than or equal to 50% decrease under baseline in the sum of products of perpendicular diameters of all measurable lesions.
No progression of evaluable disease.
For both CR and PR, no new lesions.
All assessments use the same techniques as baseline.
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Every 8 weeks during therapy
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Evaluate the toxicity of disulfiram administration
Time Frame: Lab tests-Weeks 2, 4, 8, 12, 16, 20 and 24; X-rays/scans-Every 8 weeks
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Accelerated titration designs are used for the maximum tolerated dose. Patients will remain at one dose level for one week before escalated to the next higher dose level, providing that no grade II or III toxicity occurs. Phase II is to use the maximum tolerated dose of DSF (as described above) to determine the response rate. Evaluation of toxicities will be continued. Dose reduction (switch to the next lower dose) will be carried out if patient develops grade III/IV toxicities, and this dose reduction applies to both phase I and phase II. |
Lab tests-Weeks 2, 4, 8, 12, 16, 20 and 24; X-rays/scans-Every 8 weeks
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: John Fruehauf, MD, Chao Family Comprehensive Cancer Center
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ESTIMATE)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
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
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Alcohol Deterrents
- Acetaldehyde Dehydrogenase Inhibitors
- Disulfiram
Other Study ID Numbers
- UCI 01-01
- 2001-2038 (OTHER: University of California, Irvine)
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 Stage IV Melanoma
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Emory UniversityGenentech, Inc.Active, not recruitingStage IV Skin Melanoma | Stage IIIB Skin Melanoma | Stage IIIC Skin Melanoma | Unresectable Melanoma | Stage III Melanoma | Stage IIIA Skin Melanoma | Cutaneous Melanoma, Stage III | Cutaneous Melanoma, Stage IVUnited States
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Roswell Park Cancer InstituteNational Cancer Institute (NCI); National Comprehensive Cancer NetworkTerminatedRecurrent Melanoma | Stage IV Melanoma | Metastatic Intraocular Melanoma | Recurrent Intraocular Melanoma | Stage IV Intraocular Melanoma | Stage IIIA Melanoma | Stage IIIB Melanoma | Stage IIIC Melanoma | Extraocular Extension Melanoma | Stage IIIA Intraocular Melanoma | Stage IIIB Intraocular Melanoma | Stage...United States
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Mayo ClinicNational Cancer Institute (NCI)CompletedRecurrent Melanoma | Stage IV Melanoma | Stage IIIA Melanoma | Stage IIIB Melanoma | Stage IIIC Melanoma | Stage IIB Melanoma | Stage IIC Melanoma | Stage IIA MelanomaUnited States
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M.D. Anderson Cancer CenterNational Cancer Institute (NCI)CompletedStage IV Cutaneous Melanoma AJCC v6 and v7 | Ocular Melanoma | Stage IIIC Cutaneous Melanoma AJCC v7 | Cutaneous Melanoma | Mucosal Melanoma | Stage IIIB Cutaneous Melanoma AJCC v7 | Stage IV Uveal Melanoma AJCC v7 | Stage IIIB Uveal Melanoma AJCC v7 | Stage IIIC Uveal Melanoma AJCC v7 | Stage III Acral... and other conditionsUnited States
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University of Southern CaliforniaNational Cancer Institute (NCI)CompletedRecurrent Melanoma | Stage IV Melanoma | Mucosal Melanoma | Ciliary Body and Choroid Melanoma, Medium/Large Size | Ciliary Body and Choroid Melanoma, Small Size | Iris Melanoma | Metastatic Intraocular Melanoma | Recurrent Intraocular Melanoma | Stage IV Intraocular Melanoma | Stage IIIA Melanoma | Stage... and other conditionsUnited States
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Academic and Community Cancer Research UnitedNational Cancer Institute (NCI)CompletedMetastatic Melanoma | Stage IV Cutaneous Melanoma AJCC v6 and v7 | Unresectable Melanoma | Mucosal Melanoma | Stage IV Uveal Melanoma AJCC v7United States
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Fred Hutchinson Cancer CenterNational Cancer Institute (NCI); Incyte Corporation; University of VirginiaCompletedStage IV Skin Melanoma | Recurrent Melanoma | Stage IIIB Skin Melanoma | Stage IIIC Skin Melanoma | Mucosal Melanoma | Stage IV Uveal Melanoma | Stage IIIA Skin Melanoma | Stage IIIA Uveal Melanoma | Stage IIIB Uveal Melanoma | Stage IIIC Uveal Melanoma | Recurrent Uveal MelanomaUnited States
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Elizabeth Buchbinder, MDGenentech, Inc.RecruitingStage IV Melanoma | Clinical Stage III Cutaneous Melanoma AJCC v8 | Unresectable Stage III Cutaneous Melanoma | Unresectable Stage IV Cutaneous MelanomaUnited States
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M.D. Anderson Cancer CenterNational Cancer Institute (NCI)Active, not recruitingClinical Stage III Cutaneous Melanoma AJCC v8 | Pathologic Stage IIIB Cutaneous Melanoma AJCC v8 | Pathologic Stage IIIC Cutaneous Melanoma AJCC v8 | Pathologic Stage IIID Cutaneous Melanoma AJCC v8 | Pathologic Stage III Cutaneous Melanoma AJCC v8 | Pathologic Stage IIIA Cutaneous Melanoma... and other conditionsUnited States
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Yale UniversityNational Cancer Institute (NCI)CompletedRecurrent Melanoma | Stage IV Melanoma | Stage IIIA Melanoma | Stage IIIB Melanoma | Stage IIIC MelanomaUnited States
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Cervel Neurotech, Inc.Completed
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Cervel Neurotech, Inc.CompletedMajor Depressive DisorderUnited States, Australia
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Psykiatrisk Center GentofteUnknown
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Hadassah Medical OrganizationAugusta Hospital, BerlinCompletedNon-small Cell Lung CancerIsrael