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

Melanoma (Skin) Clinical Trial

Official title:

Treatment of Melanoma With Wild-type p53 and Detectable S100B Using Pentamidine: a Phase II Trial With Correlative Biomarker Endpoints

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00729807
• Other study ID #: H-29873;HP-00040559
• Secondary ID: CDR0000602047HP-
• Status: Terminated
• Phase: Phase 2
• Start date: July 2008
• Est. completion date: November 2012

Study information

• Verified date: June 2019
• Source: University of Maryland, Baltimore
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 6
• Est. completion date: November 2012
• Est. primary completion date: August 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Melanoma
• Melanoma (Skin)

Intervention

Drug:
• pentamidine

Locations

Country	Name	City	State
United States	Greenebaum Cancer Center at University of Maryland Medical Center	Baltimore	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
University of Maryland, Baltimore	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response Rate in Patients Treated With Pentamidine	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)	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	Number of Participants With Both p21 and S100B Expression in Accessible Tumor Biopsies Pre Pentamidine Exposure in Cycle 1	Core Needle Tumor Biopsy	Pre-Study, an average of 12 days
Secondary	Number of Participants With p21 and S100B Expression in Accessible Tumor Biopsies Post Pentamidine Exposure	Core needle tumor biopsy - at Day 12 at first cycle of treatment	Day 12 Cycle 1
Secondary	Expression of S100B Pre Pentamidine Exposure	Serum for S100B	Pre-Study
Secondary	Expression of S100B	Serum for S100B level	Cycle 1 Day 8, Cycle 1 Day 12, Cycle 2 Day 8, Cycle 2 Day 12
Secondary	Number of Participants With Serious and Non Serious Adverse Events	Metabolic Panel, Physical Exam, Vitals	Up to 6 months
Secondary	Time to Progression	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.	Every 8 weeks, assesed up to 6 months