Oblimersen in Treating Patients With Merkel Cell Carcinoma

Study Overview
=================
Brief Summary
-----------------
This phase II trial is studying how well oblimersen works in treating patients with Merkel cell cancer. Biological therapies, such as oblimersen, may interfere with the growth of tumor cells and slow the growth of Merkel cell carcinoma (skin cancer).

Detailed Description
-----------------
PRIMARY OBJECTIVES: I. Determine the overall response rate in patients with Merkel cell carcinoma treated with oblimersen. SECONDARY OBJECTIVES: I. Determine the time to progression in patients treated with this drug. II. Determine the response duration in patients treated with this drug. III. Determine the safety and tolerability of this drug in these patients. IV. Determine the pharmacodynamic effects of this drug on bcl-2 expression and apoptosis in tumor biopsy specimens from these patients. OUTLINE: This is an open-label, multicenter study. Patients receive oblimersen IV continuously on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Official Title
-----------------
A Phase II Study of G3139 (Genasense ™) in Patients With Merkel Cell Carcinoma

Conditions
-----------------
Recurrent Neuroendocrine Carcinoma of the Skin, Stage I Neuroendocrine Carcinoma of the Skin, Stage II Neuroendocrine Carcinoma of the Skin, Stage III Neuroendocrine Carcinoma of the Skin, Stage IV Neuroendocrine Carcinoma of the Skin

Intervention / Treatment
-----------------
* Biological: oblimersen sodium
* Other: pharmacological study
* Other: laboratory biomarker analysis


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically or cytologically confirmed Merkel cell carcinoma Metastatic OR regionally recurrent disease Localized disease not amenable to curative therapy (surgery or radiotherapy) also allowed Measurable disease At least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan No known brain metastases Previously resected or irradiated brain metastases allowed if stable for at least the past 3 months and no evidence of neurological compromise exists Performance status - Karnofsky 60-100% Absolute neutrophil count >= 1,500/mm^3 Platelet count >= 100,000/mm^3 WBC >= 3,000/mm^3 AST/ALT =< 2.5 times upper limit of normal Bilirubin normal INR =< 1.5 Creatinine normal Creatinine clearance >= 60 mL/min No atrial fibrillation unless stable for at least the past 6 months No symptomatic congestive heart failure No unstable angina pectoris No cardiac arrhythmia Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Adequate venous access No peripheral neuropathy > grade 1 No active or ongoing infection No other concurrent uncontrolled illness No prior grade 3 or 4 anaphylactic reaction to phosphorothioate oligonucleotide No psychiatric illness or social situation that would preclude study compliance More than 3 weeks since prior chemotherapy and recovered More than 3 weeks since prior radiotherapy and recovered No prior radiotherapy to 25% or more of bone marrow More than 3 weeks since prior investigational therapy and recovered No prior oblimersen No other concurrent investigational agents No concurrent anticoagulation except 1 mg of warfarin for mediport patency No concurrent combination antiretroviral therapy for HIV-positive patients

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (oblimersen sodium)<br>Patients receive oblimersen IV continuously on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. | Biological: oblimersen sodium<br>* Given IV<br>* Other names: Genasense;Other: pharmacological study<br>* Correlative studies<br>* Other names: pharmacological studies;Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate |  | Up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to progression | Progression-free survival probabilities will be computed using Kaplan-Meier methods. | Interval between the start of treatment and until the criteria for progression are met, assessed up to 3 years | 
| Occurrence of adverse events, assessed using revised NCI CTC version 3.0 |  | Within 30 days of treatment |