Stage IV MelanomaPhase 1/2NCT00256230
Disulfiram in Patients With Metastatic Melanoma
A Phase 1/2 study testing Disulfiram (DSF) in people with Stage IV Melanoma, run by John P. Fruehauf at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Stage IV Melanoma
- What is being tested?
- Disulfiram (DSF)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2002to Aug 2007
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 12Show fewer
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Chao Family Comprehensive Cancer Center
Orange, California, 92868
About this study
Official title: 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.
Read more
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.
- Conditions
- Stage IV Melanoma
- Being tested
- Disulfiram (DSF)
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Disulfiram (DSF)Drug
Also called bis(diethylthiocarbamoyl) disulfide
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.
| Study group | Role | What they receive |
|---|---|---|
| Disulfiram | Experimental | Not described Receives: Drug: Disulfiram (DSF) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine response rate
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.
Measured: Every 8 weeks during therapy
Secondary outcomes (1)
Evaluate the toxicity of disulfiram administration
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.
Measured: Lab tests-Weeks 2, 4, 8, 12, 16, 20 and 24; X-rays/scans-Every 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Nov 2005 (estimated)
- Study startJan 2002
- Primary completionAug 2007
- Study completionAug 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Stage IV MelanomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- John P. Fruehauf
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, John P. Fruehauf, University of California, Irvine
- Investigators
- John Fruehauf, MD, Principal investigator, Chao Family Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00256230
- Sponsor's protocol ID
- UCI 01-01
- Other IDs
- 2001-2038
- Status last verified
- Dec 2011
- First submitted
- 17 Nov 2005
- Last updated
- 8 Dec 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 8 Dec 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Disulfiram in Patients With Metastatic Melanoma and at Least One Prior Systemic Therapy, Phase I/II
- ClinicalTrials.gov ID
- NCT00256230
- Acronym / sponsor ID
- UCI 01-01
- Conditions
- Stage IV Melanoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 7 participants (actual)
- Lead sponsor
- John P. FruehaufUniversity, hospital or other
- Study start
- Jan 2002
- Primary completion
- Aug 2007 (actual)
- Study completion
- Aug 2007 (actual)
- First posted
- 21 Nov 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Disulfiram | Experimental | Drug: Disulfiram (DSF) |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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.
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Disulfiram (DSF)Also: bis(diethylthiocarbamoyl) disulfideDSF 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. | Drug | Disulfiram |
Primary outcome
Determine response rate
Time frame: Every 8 weeks during therapy
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.
1 secondary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Dec 2016.
Related trials for Stage IV Melanoma
RecruitingPhase 1
IL-17 Blockade to Decrease irAEs (REPLAY)
Metastatic Melanoma
RecruitingPhase 3
A Study With Combinations of Anti-LAG-3 and Anti-PD-1 Antibodies in Adult Participants With Advanced or Metastatic Melanoma (Harmony Head-to-Head)
Melanoma
RecruitingPhase 1
Pharmacokinetics, Safety, and Immunogenicity Comparison of Bmab1700 and Opdivo® as Adjuvant Monotherapy in Participants With Melanoma
Melanoma
Active, not recruitingPhase 1/2
A Study of ST-1898 for Unresectable or Metastatic Melanoma
Unresectable or Metastatic Melanoma
RecruitingPhase 2
Phase II Trial of Combination Anti-PD-1 and Aldesleukin for Metastatic Melanoma and Renal Cell Carcinoma
Metastatic Melanoma, Advanced Locoregional Melanoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
John Fruehauf, MD principal investigator
Chao Family Comprehensive Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Disulfiram (DSF) in people with Stage IV Melanoma, run by John P. Fruehauf at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Dec 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Determine response rate (time frame: Every 8 weeks during therapy). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Dec 2016.