Clinical trial NCT00052754: Gefitinib in Treating Patients With Locally Advanced or Metastatic Synovial Sarcoma
Official title: Phase II Study Of Iressa (ZD 1839) In Locally Advanced And/Or Metastatic Synovial Sarcoma Expressing HER1/EGFR1
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Sarcoma
Keywords: adult synovial sarcoma
stage III adult soft tissue sarcoma
recurrent adult soft tissue sarcoma
stage IV adult soft tissue sarcoma
Lead sponsor: European Organisation for Research and Treatment of Cancer - EORTC
Sponsor class: NETWORK
First posted: 2003-01-27
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Progression-free rate at 12 weeks
Secondary outcomes:
measure: Toxicity as assessed by CTC 2.0
measure: Response as assessed by RECIST criteria
measure: Time to onset of response
measure: Duration of response
measure: Overall survival
Other outcomes:
Locations:
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Leuven
country: Belgium
facility: U.Z. Gasthuisberg
city: Bordeaux
country: France
facility: Institut Bergonie
city: Lyon
country: France
facility: Centre Leon Berard
city: Marseille
country: France
facility: CHU de la Timone
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Paris
country: France
facility: Institut Curie - Section Medicale
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Amsterdam
country: Netherlands
facility: Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Nijmegen
country: Netherlands
facility: Nijmegen Cancer Center at Radboud University Medical Center
city: Rotterdam
country: Netherlands
facility: Daniel Den Hoed Cancer Center at Erasmus Medical Center
city: Leeds
country: United Kingdom
facility: Leeds Cancer Centre at St. James's University Hospital
state: England
city: London
country: United Kingdom
facility: Royal Marsden NHS Foundation Trust - London
state: England
city: London
country: United Kingdom
facility: Meyerstein Institute of Oncology at University College of London Hospitals
state: England
city: Manchester
country: United Kingdom
facility: Christie Hospital N.H.S. Trust
state: England
Study officials:
affiliation: Centre Leon Berard
name: Jean-Yves Blay, MD, PhD
role: STUDY_CHAIR
References:
citation: 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.