Clinical trial NCT00729807: 0794GCC: Pentamidine in Treating Patients With Relapsed or Refractory Melanoma
Official title: Treatment of Melanoma With Wild-type p53 and Detectable S100B Using Pentamidine: a Phase II Trial With Correlative Biomarker Endpoints
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Melanoma (Skin)
Keywords: recurrent melanoma
Lead sponsor: University of Maryland, Baltimore
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2008-08-08
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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.
Primary purpose: TREATMENT

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.

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 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

Primary outcomes:
measure: Response Rate in Patients Treated With Pentamidine
timeFrame: 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
Secondary outcomes:
measure: Number of Participants With Both p21 and S100B Expression in Accessible Tumor Biopsies Pre Pentamidine Exposure in Cycle 1
timeFrame: Pre-Study, an average of 12 days
measure: Number of Participants With p21 and S100B Expression in Accessible Tumor Biopsies Post Pentamidine Exposure
timeFrame: Day 12 Cycle 1
measure: Expression of S100B Pre Pentamidine Exposure
timeFrame: Pre-Study
measure: Expression of S100B
timeFrame: Cycle 1 Day 8, Cycle 1 Day 12, Cycle 2 Day 8, Cycle 2 Day 12
measure: Number of Participants With Serious and Non Serious Adverse Events
timeFrame: Up to 6 months
measure: Time to Progression
timeFrame: Every 8 weeks, assesed up to 6 months
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Greenebaum Cancer Center at University of Maryland Medical Center
state: Maryland
Study officials:
affiliation: University of Maryland Greenebaum Cancer Center
name: Edward A. Sausville, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: