- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00571116
Disulfiram Plus Arsenic Trioxide In Patients With Metastatic Melanoma and at Least One Prior Systemic Therapy
Evaluation of Disulfiram Plus Arsenic Trioxide In Patients With Metastatic Melanoma and at Least One Prior Systemic Therapy (Phase 1b)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
PRIMARY OBJECTIVES:
I. Evaluate the tolerability of disulfiram and arsenic trioxide administration as a therapeutic combination. (Phase IB)
SECONDARY OBJECTIVES:
l. Determine the response rate (complete and partial responses) and time to progression of previously treated patients with metastatic malignant melanoma when treated with disulfiram plus Arsenic Trioxide. (Phase II)
OUTLINE: This is a dose-escalation study of arsenic trioxide.
Patients receive disulfiram orally (PO) twice daily and arsenic trioxide intravenously (IV) over 1-2 hours on Monday through Friday, alternating two weeks on treatment followed by two weeks off treatment. Courses repeat every 12 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months thereafter.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
California
-
Orange, California, United States, 92868
- Chao Family Comprehensive Cancer Center, University of California, Irvine
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Subjects 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 subject's disease status must be completely assessed and reported.
- All subjects must undergo a CT of abdomen and chest within 28 days prior to registration.
- All subjects must undergo either a CT or MRI of the brain within 28 days of registration. Subjects with asymptomatic brain metastasis are eligible for this protocol but their metastasis must be clinically stable and asymptomatic. Subjects with Central Nervous System (CNS) metastasis must have been evaluated by neurosurgery prior to entry to confirm that they are a candidate for this trial. Treatment of symptomatic CNS metastasis that is required before protocol entry.
- Subjects must have progressed based on Response Evaluation Criteria in Solid Tumors (RECIST) criteria after at least one prior systemic therapy (chemotherapy, biologic/immunotherapy, or a combination regimen) for metastatic disease. This includes development of any new lesion or a 20% increase in the sum of the subject's measurable disease compared to their previous nadir. New CNS metastasis could be the reason for disease progression, but they must be stable clinically and satisfy criteria delineated in section 5.4. Prior systemic therapy must have been completed at least 28 days before registration.
- Subjects 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
- Subjects 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 subject to be eligible. Radiation therapy must have been completed at least 28 days before registration.
- Subjects 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 Southwest Oncology Group Criteria
Performance Status:
GRADE SCALE
0 Fully active; able to carry on all pre-disease activities without restriction.
- Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light housework, office work.
- Ambulatory and capable of all self care but unable to carry out any work activities. Up and about more than 50% of waking hours.
- Capable of only limited self care; confined to bed or chair more than 50% of waking hours.
- Completely disabled. Cannot carry on any self care. Totally confined to bed or chair.
Dead
Subjects must have a normal ECG, without evidence of congestive heart failure.
- Normal heart rate (less than 100 per minute)
- Normal sinus rhythm
- Normal interval from the beginning of the Q wave to the termination of the S wave, representing the time for ventricular depolarization (QRS) interval
Subjects with QT prolongation > 500msec on their ECG will be considered ineligible.
Exclusion Criteria:
- 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.
- Subjects 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.
- Subjects who can not abstain from alcohol intake during the entire duration of this protocol are not qualified for this study.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Disulfiram and arsenic trioxide
Patients receive disulfiram 250 mg PO twice daily and arsenic trioxide IV over 1-2 hours on Monday through Friday, alternating two weeks on treatment followed by two weeks off treatment. Courses repeat every 12 weeks in the absence of disease progression or unacceptable toxicity. The Arsenic trioxide dose will be escalated or reduced until a tolerable dose is reached. Arsenic trioxide will be administered at a starting dose of 0.05 mg/kg. If the initial dose is tolerated, the patient will be dose escalated to 0.10 mg/kg/day. If the first dose escalation is tolerated, then a second dose escalation will be attempted to 0.15 mg/kg/day, the current dose recommended for leukemia. Dosing will be continued for two weeks on alternating with two weeks off as long as tolerated to a maximum of 60 doses. |
Given PO
Other Names:
Given IV
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Dose Escalation: Identification of Maximum Tolerated Dose
Time Frame: Up to 6 years
|
The dose will be escalated or reduced until a tolerable dose is reached.
Dose toleration is determined by the absence of any grade III/IV toxicities.
Arsenic trioxide will be administered intravenously at a starting dose of 0.05 mg/kg daily, 5 days per week, for 2 weeks.
The patients then have 2 weeks off, followed by two weeks of daily administration.
If the initial dose is tolerated, the patient will be dose escalated for the second two weeks of drug administration to 0.10 mg/kg/day for two additional weeks, followed by two weeks off.
If the first dose escalation is tolerated, then a second dose escalation will be attempted to 0.15 mg/kg/day, the current dose recommended for leukemia.
The 0.15 mg/kg/day dose will be continued for two weeks on alternating with two weeks off as long as this is tolerated to a maximum of 60 doses.
For patients developing grade III/IV toxicity at a given dose level, they will be dose reduced by one level and remain on that dose for the trial.
|
Up to 6 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Response rate (complete or partial response)
Time Frame: Up to 6 years
|
Will be calculated as percentage of the study population.
Data will be summarized in tabular form for publication.
|
Up to 6 years
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: John P Fruehauf, M.D. PhD, 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 (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
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Alcohol Deterrents
- Acetaldehyde Dehydrogenase Inhibitors
- Arsenic Trioxide
- Disulfiram
Other Study ID Numbers
- UCI 06-08
- 2006-5033 (Other Identifier: University of California, Irvine)
- NCI-2010-00338 (Other Identifier: NCI Clinical Trials Reporting Program (CTRP))
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
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 Metastatic Melanoma
-
Mohammed M MilhemGenentech, Inc.TerminatedMelanoma | Metastatic Melanoma | BRAF-mutated Metastatic Melanoma | V600EBRAF-mutated Metastatic MelanomaUnited States
-
National Cancer Institute (NCI)TerminatedMetastatic Uveal Melanoma | Metastatic Ocular MelanomaUnited States
-
Delcath Systems Inc.Active, not recruitingMetastatic Uveal Melanoma | Metastatic Ocular MelanomaUnited States
-
MorphotekTerminatedMelanoma | Metastatic Melanoma | Advanced Melanoma | Malignant Metastatic MelanomaUnited States
-
GlaxoSmithKlineWithdrawnCancer | Metastatic Uveal Melanoma | GNA11 Mutation-positive Metastatic Melanoma | GNAQ Mutation-positive Metastatic Melanoma
-
Elizabeth DavisBristol-Myers SquibbTerminatedMetastatic Melanoma | Advanced Melanoma | Metastatic Melanoma Stratified by MHC-II ExpressionUnited States
-
Mayo ClinicNational Cancer Institute (NCI)Active, not recruitingMetastatic Melanoma | Metastatic Uveal Melanoma | Unresectable Melanoma | Clinical 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... and other conditionsUnited States
-
Fred Hutchinson Cancer CenterAmazon.com Services LLCRecruitingAnatomic Stage IV Breast Cancer AJCC v8 | Prognostic Stage IV Breast Cancer AJCC v8 | Metastatic Cutaneous Melanoma | Unresectable Cutaneous Melanoma | Clinical Stage III Cutaneous Melanoma AJCC v8 | Pathologic Stage IIIC Cutaneous Melanoma AJCC v8 | Pathologic Stage IIID Cutaneous Melanoma AJCC... and other conditionsUnited States
-
Provectus Biopharmaceuticals, Inc.Active, not recruitingMetastatic Colorectal Cancer | Hepatocellular Carcinoma | Metastatic Lung Cancer | Metastatic Breast Cancer | Metastatic Melanoma | Metastatic Uveal Melanoma | Metastatic Pancreatic Cancer | Metastatic Colon Cancer | Metastatic Ocular Melanoma | Cancer Metastatic to the LiverUnited States
-
National Cancer Institute (NCI)Active, not recruitingMetastatic Cutaneous Melanoma | Clinical Stage III Cutaneous Melanoma AJCC v8 | Recurrent Cutaneous Melanoma | Clinical Stage IV Cutaneous Melanoma AJCC v8 | Recurrent Mucosal Melanoma | Metastatic Mucosal Melanoma | Non-Cutaneous Melanoma | Metastatic Non-Cutaneous Melanoma | Recurrent Non-Cutaneous...United States, Canada, Ireland
Clinical Trials on Disulfiram
-
Psykiatrisk Center GentofteUnknown
-
Yale UniversityNational Institute on Drug Abuse (NIDA)Completed
-
University of RochesterNot yet recruitingAge-Related Macular Degeneration | Retinitis Pigmentosa | Retinal Dystrophies | Alcohol Use Disorder | Stargardt DiseaseUnited States
-
University of WashingtonRecruitingInherited Retinal Dystrophy Primarily Involving Sensory RetinaUnited States
-
Hadassah Medical OrganizationAugusta Hospital, BerlinCompletedNon-small Cell Lung CancerIsrael
-
Baylor College of MedicineCompletedCocaine AddictionUnited States
-
University of UtahCompleted
-
John P. FruehaufCompleted
-
Universidad de GuanajuatoLaboratorios Doctor MacíasEnrolling by invitation
-
First People's Hospital of HangzhouCollege of Pharmaceutical Sciences at Zhejiang University; The Innovation Institute...Not yet recruitingChemotherapy;Advanced Gastric Cancer;Cisplatin;DisulfiramChina