Description:
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.
Title
- 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
Clinical Trial IDs
- ORG STUDY ID:
H-29873;HP-00040559
- SECONDARY ID:
CDR0000602047
- SECONDARY ID:
HP-00047658
- SECONDARY ID:
CINJ-090803
- SECONDARY ID:
0220090161
- SECONDARY ID:
R21CA135624
- NCT ID:
NCT00729807
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| pentamidine | | Pentamidine |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Pentamidine | Experimental | | |
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
| Maximum Eligible Age: | 120 Years |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Response Rate in Patients Treated With Pentamidine |
| 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 |
| Safety Issue: | |
| 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) |
Secondary Outcome Measures
| Measure: | Number of Participants With Both p21 and S100B Expression in Accessible Tumor Biopsies Pre Pentamidine Exposure in Cycle 1 |
| Time Frame: | Pre-Study, an average of 12 days |
| Safety Issue: | |
| Description: | Core Needle Tumor Biopsy |
| Measure: | Number of Participants With p21 and S100B Expression in Accessible Tumor Biopsies Post Pentamidine Exposure |
| Time Frame: | Day 12 Cycle 1 |
| Safety Issue: | |
| Description: | Core needle tumor biopsy - at Day 12 at first cycle of treatment |
| Measure: | Expression of S100B Pre Pentamidine Exposure |
| Time Frame: | Pre-Study |
| Safety Issue: | |
| Description: | Serum for S100B |
| Measure: | Expression of S100B |
| Time Frame: | Cycle 1 Day 8, Cycle 1 Day 12, Cycle 2 Day 8, Cycle 2 Day 12 |
| Safety Issue: | |
| Description: | Serum for S100B level |
| Measure: | Number of Participants With Serious and Non Serious Adverse Events |
| Time Frame: | Up to 6 months |
| Safety Issue: | |
| Description: | Metabolic Panel, Physical Exam, Vitals |
| Measure: | Time to Progression |
| Time Frame: | Every 8 weeks, assesed up to 6 months |
| Safety Issue: | |
| 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. |
Details
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Terminated |
| Lead Sponsor: | University of Maryland, Baltimore |
Trial Keywords
Last Updated
August 16, 2019
