0794GCC: Pentamidine in Treating Patients With Relapsed or Refractory Melanoma
Primary Purpose
Melanoma (Skin)
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
pentamidine
Sponsored by

About this trial
This is an interventional treatment trial for Melanoma (Skin) focused on measuring recurrent melanoma
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
Sites / Locations
- Greenebaum Cancer Center at University of Maryland Medical Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Pentamidine
Arm Description
Outcomes
Primary Outcome Measures
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)
Secondary Outcome Measures
Number of Participants With Both p21 and S100B Expression in Accessible Tumor Biopsies Pre Pentamidine Exposure in Cycle 1
Core Needle Tumor Biopsy
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
Expression of S100B Pre Pentamidine Exposure
Serum for S100B
Expression of S100B
Serum for S100B level
Number of Participants With Serious and Non Serious Adverse Events
Metabolic Panel, Physical Exam, Vitals
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.
Full Information
NCT ID
NCT00729807
First Posted
August 7, 2008
Last Updated
August 14, 2019
Sponsor
University of Maryland, Baltimore
Collaborators
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT00729807
Brief Title
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
2. Study Status
Record Verification Date
June 2019
Overall Recruitment Status
Terminated
Why Stopped
Study was closed at the suggestion of DSMB prior to obtaining target enrollment
Study Start Date
July 2008 (Actual)
Primary Completion Date
August 2012 (Actual)
Study Completion Date
November 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Maryland, Baltimore
Collaborators
National Cancer Institute (NCI)
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Melanoma (Skin)
Keywords
recurrent melanoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
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)
Allocation
N/A
Enrollment
6 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Pentamidine
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
pentamidine
Primary Outcome Measure Information:
Title
Response Rate in Patients Treated With Pentamidine
Description
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)
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
Secondary Outcome Measure Information:
Title
Number of Participants With Both p21 and S100B Expression in Accessible Tumor Biopsies Pre Pentamidine Exposure in Cycle 1
Description
Core Needle Tumor Biopsy
Time Frame
Pre-Study, an average of 12 days
Title
Number of Participants With p21 and S100B Expression in Accessible Tumor Biopsies Post Pentamidine Exposure
Description
Core needle tumor biopsy - at Day 12 at first cycle of treatment
Time Frame
Day 12 Cycle 1
Title
Expression of S100B Pre Pentamidine Exposure
Description
Serum for S100B
Time Frame
Pre-Study
Title
Expression of S100B
Description
Serum for S100B level
Time Frame
Cycle 1 Day 8, Cycle 1 Day 12, Cycle 2 Day 8, Cycle 2 Day 12
Title
Number of Participants With Serious and Non Serious Adverse Events
Description
Metabolic Panel, Physical Exam, Vitals
Time Frame
Up to 6 months
Title
Time to Progression
Description
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.
Time Frame
Every 8 weeks, assesed up to 6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
120 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Edward A. Sausville, MD, PhD
Organizational Affiliation
University of Maryland Greenebaum Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Greenebaum Cancer Center at University of Maryland Medical Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
12. IPD Sharing Statement
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0794GCC: Pentamidine in Treating Patients With Relapsed or Refractory Melanoma
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