Metastatic MelanomaPhase 1NCT00571116
Disulfiram Plus Arsenic Trioxide In Patients With Metastatic Melanoma and at Least One Prior Systemic Therapy
A Phase 1 study testing Disulfiram and Arsenic trioxide in people with Metastatic Melanoma, run by University of California, Irvine at 1 site in United States.
Trial summary
This phase I trial is studying the side effects and best dose of arsenic trioxide when given together with disulfiram in treating patients with metastatic and progressive melanoma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Melanoma
- What is being tested?
- Disulfiram and Arsenic trioxide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2006to Aug 2012
- Phase
- Phase 1
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Chao Family Comprehensive Cancer Center, University of California, Irvine
Orange, California, 92868
About this study
Official title: Evaluation of Disulfiram Plus Arsenic Trioxide In Patients With Metastatic Melanoma and at Least One Prior Systemic Therapy (Phase 1b)
This phase I trial is studying the side effects and best dose of arsenic trioxide when given together with disulfiram in treating patients with metastatic and progressive melanoma. Drugs used in chemotherapy, such as disulfiram and arsenic trioxide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells.
Read the detailed description
PRIMARY OBJECTIVES:
- Evaluate the tolerability of disulfiram and arsenic trioxide administration as a therapeutic combination. (Phase IB)
SECONDARY OBJECTIVES:
- 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.
- Conditions
- Metastatic Melanoma
- Being tested
- Disulfiram, Arsenic trioxide
- Keywords
- Metastatic Melanoma, Disulfiram, Arsenic Trioxide, Metastatic Melanoma and at Least One Prior Systemic Therapy
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DisulfiramDrug
Also called Antabuse, 25953, 97-77-8, bis(diethylthiocarbamoyl) disulfide
Given PO
Arsenic trioxideDrug
Also called TRISENOX, 1327-53-3, 57974, 706363
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Disulfiram and arsenic trioxide | Experimental | 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. Receives: Drug: Disulfiram; Drug: Arsenic trioxide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose Escalation: Identification of Maximum Tolerated Dose
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.
Measured: Up to 6 years
Secondary outcomes (1)
Response rate (complete or partial response)
Will be calculated as percentage of the study population. Data will be summarized in tabular form for publication.
Measured: Up to 6 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Dec 2007 (estimated)
- Study startSep 2006
- Primary completionAug 2012
- Study completionAug 2012
Why it stopped: Halted because of slow accrual and lack of study funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic MelanomaStudies of the same condition, open and under way.
- More trials run by University of California, IrvineThe sponsor's other registered studies.
- 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, Irvine
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, John P. Fruehauf, University of California, Irvine
- Investigators
- John P Fruehauf, M.D. PhD, Principal investigator, Chao Family Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00571116
- Sponsor's protocol ID
- UCI 06-08
- Other IDs
- 2006-5033, NCI-2010-00338
- Status last verified
- May 2019
- First submitted
- 6 Dec 2007
- Last updated
- 7 Aug 2019
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Disulfiram Plus Arsenic Trioxide In Patients With Metastatic Melanoma and at Least One Prior Systemic Therapy (Phase 1b)
- ClinicalTrials.gov ID
- NCT00571116
- Acronym / sponsor ID
- UCI 06-08
- Conditions
- Metastatic Melanoma
- Keywords
- Metastatic Melanoma, Disulfiram, Arsenic Trioxide, Metastatic Melanoma and at Least One Prior Systemic Therapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Halted because of slow accrual and lack of study funding
- Enrolment
- 9 participants (actual)
- Lead sponsor
- University of California, IrvineUniversity, hospital or other
- Study start
- Sep 2006
- Primary completion
- Aug 2012 (actual)
- Study completion
- Aug 2012 (actual)
- First posted
- 11 Dec 2007 (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.
This phase I trial is studying the side effects and best dose of arsenic trioxide when given together with disulfiram in treating patients with metastatic and progressive melanoma. Drugs used in chemotherapy, such as disulfiram and arsenic trioxide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells.
Detailed description
PRIMARY OBJECTIVES:
- Evaluate the tolerability of disulfiram and arsenic trioxide administration as a therapeutic combination. (Phase IB)
SECONDARY OBJECTIVES:
- 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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Disulfiram and arsenic trioxide | Experimental | Drug: Disulfiram, Drug: Arsenic trioxidePatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- 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
Key exclusion criteria (3 listed)
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 |
|---|---|---|
| DisulfiramAlso: Antabuse, 25953, 97-77-8, bis(diethylthiocarbamoyl) disulfideGiven PO | Drug | Disulfiram and arsenic trioxide |
| Arsenic trioxideAlso: TRISENOX, 1327-53-3, 57974, 706363Given IV | Drug | Disulfiram and arsenic trioxide |
Primary outcome
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.
1 secondary outcome
Response rate (complete or partial response)
Time frame: Up to 6 years
Results and safety
The study was stopped early (reason given: Halted because of slow accrual and lack of study funding). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2019.
- Individual participant dataSharing planned: No
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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 P Fruehauf, M.D. PhD 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 study testing Disulfiram and Arsenic trioxide in people with Metastatic Melanoma, run by University of California, Irvine 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 21 inclusion and 3 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: stopped early, as of the sponsor's last update on 7 Aug 2019. 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 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.
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 was stopped early (reason given: Halted because of slow accrual and lack of study funding). Results are not available in the source record.
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?
Dose Escalation: Identification of Maximum Tolerated Dose (time frame: Up to 6 years). 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 7 Aug 2019.