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

University of Maryland Baltimore (UMB)

Status and phase

Terminated

Phase 2

Conditions

Melanoma (Skin)

Treatments

Drug: pentamidine

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00729807

HP-00047658 (Other Identifier)

H-29873 HP-00040559;

CDR0000602047 (Registry Identifier)

0220090161 (Other Identifier)

CINJ-090803 (Other Identifier)

R21CA135624 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment

6 patients

Sex

All

Ages

18 to 120 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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