Oblimersen in Treating Patients With Merkel Cell Carcinoma

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

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).

Study Overview

• Status: Completed
• Conditions: Recurrent Neuroendocrine Carcinoma of the Skin; Stage III Neuroendocrine Carcinoma of the Skin; Stage IV Neuroendocrine Carcinoma of the Skin; Stage II Neuroendocrine Carcinoma of the Skin; Stage I Neuroendocrine Carcinoma of the Skin
• Intervention / Treatment: Other: laboratory biomarker analysis; Biological: oblimersen sodium; Other: pharmacological study

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.

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan-Kettering Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (oblimersen sodium); Patients receive oblimersen IV continuously on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Other: laboratory biomarker analysis; Correlative studies; Biological: oblimersen sodium; Given IV; Other Names: augmerosen; G3139; G3139 bcl-2 antisense oligodeoxynucleotide; Genasense; Other: pharmacological study; Correlative studies; Other Names: pharmacological studies

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Ki Chung, Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start: January 1, 2004
• Primary Completion (Actual): January 1, 2007

Study Registration Dates

• First Submitted: March 8, 2004
• First Submitted That Met QC Criteria: March 8, 2004
• First Posted (Estimate): March 9, 2004

Study Record Updates

• Last Update Posted (Estimate): June 4, 2013
• Last Update Submitted That Met QC Criteria: June 3, 2013
• Last Verified: June 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Virus Diseases; Infections; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; DNA Virus Infections; Tumor Virus Infections; Neuroendocrine Tumors; Polyomavirus Infections; Carcinoma; Skin Neoplasms; Carcinoma, Neuroendocrine; Carcinoma, Merkel Cell; Antineoplastic Agents; Oblimersen
• Other Study ID Numbers: NCI-2012-01446; N01CM62207 (U.S. NIH Grant/Contract); N01CM62206 (U.S. NIH Grant/Contract); 03-105; CDR0000354418; NCI-5907; MSKCC-03105