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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

About this trial

This is an interventional treatment trial for Melanoma (Skin) focused on measuring recurrent melanoma

Eligibility Criteria

18 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

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

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

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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