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Disulfiram Plus Arsenic Trioxide In Patients With Metastatic Melanoma and at Least One Prior Systemic Therapy

This study has been terminated.
(Halted because of slow accrual and lack of study funding)
Sponsor:
Information provided by (Responsible Party):
Chao Family Comprehensive Cancer Center, University of California, Irvine
ClinicalTrials.gov Identifier:
NCT00571116
First received: December 6, 2007
Last updated: April 3, 2013
Last verified: April 2013
  Purpose

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.


Condition Intervention Phase
Metastatic Melanoma
Drug: Disulfiram
Drug: Arsenic trioxide
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Evaluation of Disulfiram Plus Arsenic Trioxide In Patients With Metastatic Melanoma and at Least One Prior Systemic Therapy (Phase 1b)

Resource links provided by NLM:


Further study details as provided by University of California, Irvine:

Primary Outcome Measures:
  • Tolerability of disulfiram in combination with arsenic trioxide [ Time Frame: Up to 6 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Response rate (complete or partial response) [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
    Will be calculated as percentage of the study population. Data will be summarized in tabular form for publication.


Enrollment: 15
Study Start Date: September 2006
Study Completion Date: August 2012
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Disulfiram and arsenic trioxide
Patients receive disulfiram 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.
Drug: Disulfiram
Given PO
Other Names:
  • Antabuse
  • 25953
  • 97-77-8
  • bis(diethylthiocarbamoyl) disulfide
  • DS
  • tetraethylthioperoxydicarbonic diamide
  • tetraethylthiuram disulfide
  • Teturamin
  • TTD
Drug: Arsenic trioxide
Given IV
Other Names:
  • TRISENOX
  • 1327-53-3
  • 57974
  • 706363
  • Arsenic (III) Oxide
  • Arsenic Sesquioxide
  • Arsenous Acid
  • Arsenous Acid Anhydride
  • Arsenous Oxide
  • AS2O3
  • White Arsenic

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.

  1. 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.
  2. Ambulatory and capable of all self care but unable to carry out any work activities. Up and about more than 50% of waking hours.
  3. Capable of only limited self care; confined to bed or chair more than 50% of waking hours.
  4. Completely disabled. Cannot carry on any self care. Totally confined to bed or chair.
  5. Dead

    • Subjects must have a normal ECG, without evidence of congestive heart failure.

      1. Normal heart rate (less than 100 per minute)
      2. Normal sinus rhythm
      3. Normal interval from the beginning of the Q wave to the termination of the S wave, representing the time for ventricular depolarization (QRS) interval
      4. 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00571116

Locations
United States, California
Chao Family Comprehensive Cancer Center, University of California, Irvine
Orange, California, United States, 92868
Sponsors and Collaborators
University of California, Irvine
Investigators
Principal Investigator: John P Fruehauf, M.D. PhD Chao Family Comprehensive Cancer Center
  More Information

No publications provided

Responsible Party: Chao Family Comprehensive Cancer Center, User Account Contact, University of California, Irvine
ClinicalTrials.gov Identifier: NCT00571116     History of Changes
Other Study ID Numbers: UCI 06-08, 2006-5033, NCI-2010-00338
Study First Received: December 6, 2007
Last Updated: April 3, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of California, Irvine:
Metastatic Melanoma
Disulfiram
Arsenic Trioxide
Metastatic Melanoma and at Least One Prior Systemic Therapy

Additional relevant MeSH terms:
Melanoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neuroectodermal Tumors
Neuroendocrine Tumors
Nevi and Melanomas
Arsenic trioxide
Disulfiram
Alcohol Deterrents
Antineoplastic Agents
Central Nervous System Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014