Evaluation of Trastuzumab In Patients With HER2 Positive Persistent Or Recurrent Vulvar Paget's Disease

A Phase II Evaluation of Trastuzumab In Patients With HER2 Positive Persistent Or Recurrent Vulvar Paget's Disease

This is a phase II open-label study of the activity and safety of trastuzumab in patients with vulvar Paget's disease with overexpression of HER2 on biopsy.

Study Overview

• Status: Withdrawn
• Conditions: Paget's Disease of the Vulva
• Intervention / Treatment: Drug: trastuzumab

Detailed Description

The primary objective will be to estimate the anti-tumor activity of trastuzumab by evaluating the response to trastuzumab therapy in patients with recurrent or persistent vulvar Paget's disease demonstrating HER2/neu overexpression by immunohistochemistry and/ or FISH ((fluorescence in situ hybridization).

The secondary objectives:

• To evaluate the quality of life, based on the severity of the patients' vulvar itching on a 4-point verbal rating scale from 0 to 3 (0=no itching, 1=mild itching/ bothersome, 2=moderate itching/ troublesome, 3=severe itching/ extremely troublesome) as well as on the severity of the patients' vulvar pain on a numeric pain scale from 0-10 (0=no pain, 1-3=mild pain, 4-6=moderate pain, 7-10=severe pain).
• To assess the frequency and severity of observed adverse effects
• To assess the frequency/ incidence of HER2 in Paget's disease of the vulva

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Smilow Cancer Hospital at Yale New Haven

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• recurrent or persistent vulvar Paget's disease with overexpression of HER2 by immunohistochemistry and or fluorescence in situ hybridization (FISH)
• Biopsy for histologic confirmation
• Measurable disease
• Karnofsky score of 50-100
• recovered from effects of recent surgery, radiotherapy, or chemotherapy
• free of active infection requiring antibiotics
• adequate bone marrow function,renal function,hepatic function,cardiac function,WOCBP-neg.serum pregnancy,meet requirements in section 7.0

Exclusion Criteria:

• no measurable disease
• tumors not HER2 positive by immunohistochemistry FISH
• prior therapy with any anti-HER2 monoclonal antibody preparation
• Karnofsky score of 0-40
• other invasive malignancies, with the exception of non-melanoma skin cancer
• Patients requiring supplemental oxygen
• unstable medical conditions in the opinion of the treating physician place them at unacceptably increased risk from trastuzumab therapy
• Patients with active or unstable cardiac disease, or myocardial infarction within 6 months

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: Trastuzumab; Open Label	Drug: trastuzumab; monoclonal antibody

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
measurement of the longest diameter for all target lesions	Where possible measurement of the target lesion size in 2 perpendicular diameters will be required for follow up. A Change in the product of these 2 diameters affords some estimate of change in tumor size and hence therapeutic efficacy. Response criteria will be based on the RECIST modified response evaluation criteria (appendix I).The reporting of these changes will be on an individual case basis and will be in terms of the best response achieved by that case.	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the safety profile of trastuzumab in persistent or recurrent vulvar Paget's disease	To assess the safety profile for all patients who receive any amount of trastuzumab will be evaluable for toxicity.At each visit, a brief focused history will be obtained and any indication of treatment related toxicity will be evaluated by appropriate examination and/or laboratory/radiographic studies using the CTCAE v4.0 toxicity grades for both laboratory and non-laboratory data.The evaluation period should extend from date of first treatment until 30 days (or longer if so specified) from the last dose, or until resolution from all acute toxicities associated with the drug administration.	5 years

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: Genentech, Inc.
• Investigators: Principal Investigator: Thomas J. Rutherford, MD, PhD, Yale University

Study record dates

Study Major Dates

• Study Start: August 1, 2011
• Primary Completion (Anticipated): September 1, 2014
• Study Completion (Anticipated): September 1, 2015

Study Registration Dates

• First Submitted: August 31, 2011
• First Submitted That Met QC Criteria: August 31, 2011
• First Posted (Estimate): September 1, 2011

Study Record Updates

• Last Update Posted (Estimate): June 16, 2014
• Last Update Submitted That Met QC Criteria: June 12, 2014
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Keywords: HER2 positive; HER2+; HER2 overexpression; measurable disease; Histologic confirmation; persistent vulvar Paget's disease; recurrent vulvar Paget's disease
• Additional Relevant MeSH Terms: Antineoplastic Agents; Antineoplastic Agents, Immunological; Trastuzumab
• Other Study ID Numbers: 1004006704