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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00729807
Recruitment Status : Terminated (Study was closed at the suggestion of DSMB prior to obtaining target enrollment)
First Posted : August 8, 2008
Results First Posted : October 21, 2016
Last Update Posted : August 16, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University of Maryland, Baltimore

Brief Summary:

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 or disease Intervention/treatment Phase
Melanoma (Skin) Drug: pentamidine Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 6 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: This is an open label Phase II trial that will utilize a Simon two stage acquisition of patients with evaluable relapsed and/or refractory melanoma.
Masking: None (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
Actual Study Start Date : July 2008
Actual Primary Completion Date : August 2012
Actual Study Completion Date : November 2012


Arm Intervention/treatment
Experimental: Pentamidine Drug: pentamidine



Primary Outcome Measures :
  1. Response Rate in Patients Treated With Pentamidine [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months ]
    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 :
  1. Number of Participants With Both p21 and S100B Expression in Accessible Tumor Biopsies Pre Pentamidine Exposure in Cycle 1 [ Time Frame: Pre-Study, an average of 12 days ]
    Core Needle Tumor Biopsy

  2. Number of Participants With p21 and S100B Expression in Accessible Tumor Biopsies Post Pentamidine Exposure [ Time Frame: Day 12 Cycle 1 ]
    Core needle tumor biopsy - at Day 12 at first cycle of treatment

  3. Expression of S100B Pre Pentamidine Exposure [ Time Frame: Pre-Study ]
    Serum for S100B

  4. Expression of S100B [ Time Frame: Cycle 1 Day 8, Cycle 1 Day 12, Cycle 2 Day 8, Cycle 2 Day 12 ]
    Serum for S100B level

  5. Number of Participants With Serious and Non Serious Adverse Events [ Time Frame: Up to 6 months ]
    Metabolic Panel, Physical Exam, Vitals

  6. Time to Progression [ Time Frame: Every 8 weeks, assesed up to 6 months ]

    Radiologic intervention using RECIST (x-ray, CT, MRI)

    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; Overall Response (OR) = CR + PR.", or similar definition that is accurate and appropriate.




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Ages Eligible for Study:   18 Years to 120 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00729807


Locations
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United States, Maryland
Greenebaum Cancer Center at University of Maryland Medical Center
Baltimore, Maryland, United States, 21201
Sponsors and Collaborators
University of Maryland, Baltimore
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Edward A. Sausville, MD, PhD University of Maryland Greenebaum Cancer Center
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Responsible Party: University of Maryland, Baltimore
ClinicalTrials.gov Identifier: NCT00729807    
Other Study ID Numbers: H-29873;HP-00040559
CDR0000602047 ( Registry Identifier: PDQ (Physician Data Query) )
HP-00047658 ( Other Identifier: University of Maryland Human Research Protections Office )
CINJ-090803 ( Other Identifier: Cancer Institute of New Jersey )
0220090161 ( Other Identifier: UMDNJ IRB Number )
R21CA135624 ( U.S. NIH Grant/Contract )
First Posted: August 8, 2008    Key Record Dates
Results First Posted: October 21, 2016
Last Update Posted: August 16, 2019
Last Verified: June 2019
Keywords provided by University of Maryland, Baltimore:
recurrent melanoma
Additional relevant MeSH terms:
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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