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0794GCC: Pentamidine in Treating Patients With Relapsed or Refractory Melanoma

This study has been completed.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Edward Sausville, University of Maryland
ClinicalTrials.gov Identifier:
NCT00729807
First received: August 7, 2008
Last updated: August 30, 2016
Last verified: August 2016
  Purpose

RATIONALE: Drugs used in chemotherapy, such as pentamidine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

PURPOSE: This phase II trial is studying how well pentamidine works in treating patients with relapsed or refractory melanoma.


Condition Intervention Phase
Melanoma (Skin)
Drug: pentamidine
Genetic: gene expression analysis
Genetic: polymerase chain reaction
Genetic: western blotting
Other: bioluminescence
Other: immunoenzyme technique
Other: immunohistochemistry staining method
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Treatment of Melanoma With Wild-type p53 and Detectable S100B Using Pentamidine: a Phase II Trial With Correlative Biomarker Endpoints

Resource links provided by NLM:


Further study details as provided by University of Maryland:

Primary Outcome Measures:
  • CR, PR, Stable Disease [ Time Frame: Every 6-8 weeks ] [ Designated as safety issue: No ]
    Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease, neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease, taking as reference the smallest sum of the longest diameter since the treatment started. (Therasse, P., Arbuck, S.G., Eisenhauer, E.A., Wanders, J., Kaplan, R.S., Rubinstein, J., Van Glabbeke, M., van Oosterom, A.T., Christian, M.C., Gwyther, S.G. (2000) J Natl Cancer Inst 92, 205-16)


Secondary Outcome Measures:
  • Wild-type p53 and S100B Status at Baseline [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Zero participants analyzed. Data was not analyzed owing to the small number of patients actually treated with pentamidine; most patients screened could not enter owing to inability to define p53 status in a timely fashion and emergence of immunotherapeutics as an active modality in melanoma. Data Safety Monitoring board recommended closure to accrual after documentation of hypotensions and hypoglycemia in the small cohort of patients actually treated.

  • Serial Serum S100B Levels [ Time Frame: Days 3, 8, and 12 of Cycles 1 and 2 ] [ Designated as safety issue: No ]
    Zero participants analyzed. Data was not analyzed owing to the small number of patients actually treated with pentamidine; most patients screened could not enter owing to inability to define p53 status in a timely fashion and emergence of immunotherapeutics as an active modality in melanoma. Data Safety Monitoring board recommended closure to accrual after documentation of hypotension and hypoglycemia in the small cohort of patients actually treated.

  • Pre- and Post-treatment Changes in the Concentration of S100B and p21 in Tumor Biopsy Samples [ Time Frame: pre- and pos-treatment ] [ Designated as safety issue: No ]
    Zero participants analyzed. Data was not analyzed owing to the small number of patients actually treated with pentamidine; most patients screened could not enter owing to inability to define p53 status in a timely fashion and emergence of immunotherapeutics as an active modality in melanoma. Data Safety Monitoring board recommended closure to accrual after documentation of hypotension and hypoglycemia in the small cohort of patients actuallyly treated.

  • Progression Time in Patients [ Time Frame: pre- to post-treatment ] [ Designated as safety issue: No ]
    To observe the time to progression in these patients. However, in the six patients treated they either all had progression of disease or stable when they came off study (i.e., the drug did not work, there was no basis to collect the data to time to progression (they went on to different treatments or hospice.) One patient was inevaluable due to going on hospice, four had disease progression disease and one had stable disease and patients must come off per protocol if they do not show a response to the drug.


Enrollment: 6
Study Start Date: July 2008
Study Completion Date: November 2012
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pentamidine
4 mg/kg/day IV pentamidine isethionate infused slowly over 2 hours. Each treatment cycle will consist of 2 weeks of therapy, five days per week, followed by 2 weeks of observation.
Drug: pentamidine Genetic: gene expression analysis Genetic: polymerase chain reaction Genetic: western blotting Other: bioluminescence Other: immunoenzyme technique Other: immunohistochemistry staining method Other: laboratory biomarker analysis

Detailed Description:

OBJECTIVES:

Primary

  • To determine the response rate in patients with relapsed or refractory melanoma that expresses wild-type p53 and S100 calcium binding protein B (S100B) treated with pentamidine.

Secondary

  • To observe the effect of this drug on the expression of S100B and p21 in tumor biopsy samples.
  • To observe the effect of this drug on S100B detectable in serum.
  • To observe the time to progression in these patients.
  • To assess the toxicities associated with the administration of this drug in these patients.

OUTLINE: Patients receive pentamidine IV over 2 hours 5 days a week for 2 weeks. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Patients undergo tumor tissue and blood sample collection periodically for correlative laboratory studies. Samples are assessed for p53 status and S100B, p53, and p21 expression by immunohistochemistry, polymerase chain reaction, western blotting, luminescence assay, and ELISA.

After completion of study treatment, patients are followed for 30 days.

  Eligibility

Ages Eligible for Study:   18 Years to 120 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed melanoma

    • Relapsed or refractory disease
  • Tumor expresses wild-type p53
  • Measurable S100B by immunohistochemistry
  • Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 20 mm by conventional techniques or as ≥ 10 mm by spiral CT scan
  • Tumor amenable to biopsy
  • Must have been evaluated for potentially curative resection
  • No unstable or symptomatic brain metastases (e.g., seizures, headache related to tumor, or presence of neurologic deficits attributable to tumor)

    • Patients with stable brain metastases (by CT scan or MRI) are eligible provided they were treated with local therapy > 4 weeks ago AND do not require maintenance steroid treatment

PATIENT CHARACTERISTICS:

  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Life expectancy > 12 weeks
  • White Blood Cell count (WBC) ≥ 3,000/mcL
  • Absolute Neutrophil Count (ANC) ≥ 1,500/mcL
  • Platelet count ≥ 80,000/mcL
  • Hemoglobin ≥ 8 g/dL
  • Total bilirubin ≤ 1.5 times normal
  • aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 times upper limit of normal
  • Creatinine ≤ 1.5 times normal or creatinine clearance ≥ 60 mL/min
  • Not pregnant or nursing
  • Fertile patients must use effective contraception during and for ≥ 3 months after completion of study treatment
  • Able to take oral medications on a regular basis
  • No history of allergic reactions attributed to pentamidine
  • Mean Corrected QT Interval (QTc) ≤ 470 msec (with Bazett's correction) on screening ECG
  • No history of familial long QT syndrome
  • Proteinuria ≤ 1 on two consecutive dipsticks taken ≥ 1 week apart
  • No concurrent uncontrolled illness including, but not limited to, any of the following:

    • Hypertension
    • Ongoing or active infection
    • Symptomatic congestive heart failure
    • Unstable angina pectoris
    • Renal failure
    • Cardiac arrhythmia
    • Psychiatric illness/social situations that would limit compliance with study requirements

PRIOR CONCURRENT THERAPY:

  • Recovered from all prior therapy
  • Any number of prior chemotherapy regimens allowed
  • More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C)
  • More than 4 weeks since prior radiotherapy or major surgery
  • More than 30 days since prior participation in an investigational trial
  • No concurrent medication that may markedly affect renal function (e.g., vancomycin, amphotericin, zoledronic acid)
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • No other concurrent investigational agents
  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: NCT00729807

Locations
United States, Maryland
Greenebaum Cancer Center at University of Maryland Medical Center
Baltimore, Maryland, United States, 21201
Sponsors and Collaborators
Edward Sausville
National Cancer Institute (NCI)
Investigators
Principal Investigator: Edward A. Sausville, MD, PhD University of Maryland Greenebaum Cancer Center
  More Information

Responsible Party: Edward Sausville, Principal Investigator, University of Maryland
ClinicalTrials.gov Identifier: NCT00729807     History of Changes
Other Study ID Numbers: H-29873;HP-00040559  CDR0000602047  HP-00047658  CINJ-090803  0220090161  R21CA135624 
Study First Received: August 7, 2008
Results First Received: December 17, 2015
Last Updated: August 30, 2016
Health Authority: United States: Data and Safety Monitoring Board
United States: Federal Government
United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by University of Maryland:
recurrent melanoma

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Pentamidine
Antifungal Agents
Anti-Infective Agents
Antiprotozoal Agents
Antiparasitic Agents
Trypanocidal Agents

ClinicalTrials.gov processed this record on December 02, 2016