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

NCT00729807 | Terminated Phase 2 Results DMC

• 6 other identifiers: H-29873;HP-00040559CDR0000602047HP-00047658CINJ-0908030220090161R21CA135624
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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.

Conditions

Melanoma (Skin)

Keywords

recurrent melanoma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Number of Participants With Both p21 and S100B Expression in Accessible Tumor Biopsies Pre Pentamidine Exposure in Cycle 1

  Pre-Study, an average of 12 days

• Number of Participants With p21 and S100B Expression in Accessible Tumor Biopsies Post Pentamidine Exposure

  Day 12 Cycle 1

• Expression of S100B Pre Pentamidine Exposure

  Pre-Study

• Expression of S100B

  Cycle 1 Day 8, Cycle 1 Day 12, Cycle 2 Day 8, Cycle 2 Day 12

• Number of Participants With Serious and Non Serious Adverse Events

  Up to 6 months

Study Arms (1)

Pentamidine

EXPERIMENTAL

Drug: pentamidine

Interventions

pentamidine DRUG

Pentamidine

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• University of Maryland, Baltimore: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Greenebaum Cancer Center at University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

Pentamidine

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Benzamidines; Amidines; Organic Chemicals

Limitations and Caveats

Unable to reach the target number of participants needed before study was closed at the suggestion of DSMB

Results Point of Contact

• Title: Edward A. Sausville, M.D., Ph.D.
• Organization: University of Maryland Greenebaum Cancer Center

esausville@umm.edu

410-328-7394

Study Officials

• Edward A. Sausville, MD, PhD

  University of Maryland Greenebaum Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: August 7, 2008
• First Posted: August 8, 2008
• Study Start: July 1, 2008
• Primary Completion: August 1, 2012
• Study Completion: November 1, 2012
• Last Updated: August 16, 2019
• Results First Posted: October 21, 2016

Record last verified: 2019-06

Locations

US (1)