Gefitinib in Treating Patients With Locally Advanced or Metastatic Synovial Sarcoma

Phase II Study Of Iressa (ZD 1839) In Locally Advanced And/Or Metastatic Synovial Sarcoma Expressing HER1/EGFR1

RATIONALE: Biological therapies such as gefitinib may interfere with the growth of the tumor cells and slow the growth of synovial sarcoma.

PURPOSE: Phase II trial to study the effectiveness of gefitinib in treating patients who have locally advanced or metastatic synovial sarcoma.

Study Overview

• Status: Completed
• Conditions: Sarcoma
• Intervention / Treatment: Drug: gefitinib

Detailed Description

OBJECTIVES:

• Determine the therapeutic activity of gefitinib, in terms of progression-free rate, in patients with locally advanced or metastatic synovial sarcoma expressing HER1.
• Determine the toxicity of this drug in these patients.
• Determine the objective response, in terms of time to onset and duration of response, in patients treated with this drug.
• Determine the overall survival of patients treated with this drug.

OUTLINE: This is a non-randomized, multicenter study.

Patients receive oral gefitinib twice daily. Treatment continues in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 14-44 patients will be accrued for this study within 18 months.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1200
    • Cliniques universitaires Saint-Luc
  • Leuven, Belgium, B-3000
    • U.Z. Gasthuisberg
• France
  • Bordeaux, France, 33076
    • Institut Bergonie
  • Lyon, France, 69373
    • Centre Léon Bérard
  • Marseille, France, 13385
    • CHU de la Timone
  • Nice, France, 06189
    • Centre Antoine Lacassagne
  • Paris, France, 75248
    • Institut Curie - Section Medicale
  • Villejuif, France, F-94805
    • Institut Gustave Roussy
• Netherlands
  • Amsterdam, Netherlands, 1066 CX
    • Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital
  • Leiden, Netherlands, 2300 RC
    • Leiden University Medical Center
  • Nijmegen, Netherlands, NL-6500 HB
    • Nijmegen Cancer Center at Radboud University Medical Center
  • Rotterdam, Netherlands, 3008 AE
    • Daniel Den Hoed Cancer Center at Erasmus Medical Center
• United Kingdom
  • England
    • Leeds, England, United Kingdom, LS9 7TF
      • Leeds Cancer Centre at St. James's University Hospital
    • London, England, United Kingdom, SW3 6JJ
      • Royal Marsden NHS Foundation Trust - London
    • London, England, United Kingdom, WIT 3AA
      • Meyerstein Institute of Oncology at University College of London Hospitals
    • Manchester, England, United Kingdom, M20 4BX
      • Christie Hospital N.H.S. Trust

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

DISEASE CHARACTERISTICS:

• Histologically proven advanced or metastatic synovial sarcoma that is not amenable to surgery, radiotherapy, or combined modality treatment with curative intent
• HER1 antigen expression
• Must have received at least 1 prior chemotherapy regimen comprising doxorubicin and/or ifosfamide

• At least 1 measurable lesion with evidence of progression within 3 months of study

  • Osseous lesions and pleural effusions are not considered measurable
• No symptomatic or known CNS metastases

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• WHO 0-2

Life expectancy

• Not specified

Hematopoietic

• WBC greater than 3,000/mm^3
• Granulocyte count greater than 1,000/mm^3
• Platelet count greater than 100,000/mm^3

Hepatic

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• Albumin at least 25 g/L

Renal

• Creatinine no greater than 2 times ULN OR
• Creatinine clearance greater than 65 mL/min

Cardiovascular

• No history of severe cardiovascular disease

Pulmonary

• No evidence of clinically active interstitial lung disease

  • Asymptomatic chronic stable radiographic changes allowed

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception
• No known severe hypersensitivity to gefitinib or any of its excipients
• No other primary malignant tumor except adequately treated carcinoma in situ of the cervix, basal cell skin cancer, or any other malignant tumor in complete remission for at least 3 years
• No other severe medical illness
• No psychosis
• No psychological, familial, sociological, or geographical condition that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• See Disease Characteristics
• At least 28 days since prior chemotherapy and recovered

Endocrine therapy

• Not specified

Radiotherapy

• At least 3 months since prior radiotherapy to measurable lesion and recovered
• No concurrent radiotherapy for soft tissue sarcoma
• Concurrent palliative radiotherapy to nontarget lesions allowed

Surgery

• Not specified

Other

• More than 28 days since prior unapproved or investigational drugs and recovered
• No concurrent phenytoin, carbamazepine, rifampin, barbiturates, or Hypericum perforatum (St. John's Wort)
• No other concurrent cytostatic agents
• No other concurrent tyrosine kinase activity inhibitors
• No other concurrent systemic therapy for soft tissue sarcoma

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Masking: NONE

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Progression-free rate at 12 weeks

Secondary Outcome Measures

Outcome Measure
Overall survival
Duration of response
Toxicity as assessed by CTC 2.0
Response as assessed by RECIST criteria
Time to onset of response

Collaborators and Investigators

• Sponsor: European Organisation for Research and Treatment of Cancer - EORTC
• Investigators: Study Chair: Jean-Yves Blay, MD, PhD, Centre Léon Bérard

Publications and helpful links

General Publications

• Ray-Coquard I, Le Cesne A, Whelan JS, Schoffski P, Bui BN, Verweij J, Marreaud S, van Glabbeke M, Hogendoorn P, Blay JY. A phase II study of gefitinib for patients with advanced HER-1 expressing synovial sarcoma refractory to doxorubicin-containing regimens. Oncologist. 2008 Apr;13(4):467-73. doi: 10.1634/theoncologist.2008-0065.

Study record dates

Study Major Dates

• Study Start: October 1, 2002
• Primary Completion (ACTUAL): October 1, 2005

Study Registration Dates

• First Submitted: January 24, 2003
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (ESTIMATE): January 27, 2003

Study Record Updates

• Last Update Posted (ESTIMATE): September 24, 2012
• Last Update Submitted That Met QC Criteria: September 20, 2012
• Last Verified: September 1, 2012

More Information

Terms related to this study

• Keywords: adult synovial sarcoma; stage IV adult soft tissue sarcoma; recurrent adult soft tissue sarcoma; stage III adult soft tissue sarcoma
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Connective Tissue; Sarcoma; Sarcoma, Synovial; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Gefitinib
• Other Study ID Numbers: EORTC-62022