Clinical trial NCT00104949: Trastuzumab in Treating Patients With Locally Advanced or Metastatic Synovial Sarcoma
Official title: Phase II Study of Trastuzumab (NSC-688097) in Treatment of Locally Advanced or Metastatic Synovial Sarcoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Sarcoma
Keywords: adult synovial sarcoma
recurrent adult soft tissue sarcoma
stage III adult soft tissue sarcoma
stage IV adult soft tissue sarcoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: National Cancer Institute (NCI)
First posted: 2005-03-04
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: RATIONALE: Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Trastuzumab may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase II trial is studying how well trastuzumab works in treating patients with locally advanced or metastatic synovial sarcoma.

Detailed description: OBJECTIVES:

Primary

* Determine the response rate (confirmed complete response and partial response) in patients with HER2/neu-overexpressing locally advanced or metastatic synovial sarcoma treated with trastuzumab (Herceptin\^®).

Secondary

* Determine the frequency and severity of toxic effects of this drug in these patients.
* Determine overall survival and progression-free survival of patients treated with this drug.
* Correlate, preliminarily, SYT-SSX translocation, HER2/neu expression, and monophasic and biphasic phenotype with clinical outcomes in patients treated with this drug.

OUTLINE: This is a pilot, multicenter study.

Patients receive trastuzumab (Herceptin\^®) IV over 90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 6 weeks until disease progression and then every 6 months for up to 2 years from study entry.

PROJECTED ACCRUAL: A total of 20-40 patients will be accrued for this study within 10-40 months.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed synovial sarcoma meeting 1 of the following stage criteria:

  * Locally advanced disease, defined as 1 of the following:

    * Incurable by conventional multidisciplinary therapy, including surgery
    * Surgically resectable only with significant morbidity
  * Metastatic disease
* Tumor HER2/neu positive (2+ or 3+) by immunohistochemistry
* Tumor tissue must be available AND patient must be willing to allow specimen submission
* Measurable disease
* No known CNS metastases

PATIENT CHARACTERISTICS:

Age

* 18 and over

Performance status

* Zubrod 0-2

Life expectancy

* Not specified

Hematopoietic

* Absolute neutrophil count \> 1,000/mm\^3
* Hemoglobin \> 8 g/dL
* Platelet count \> 100,000/mm\^3

Hepatic

* Bilirubin \< 1.5 times upper limit of normal (ULN)
* SGOT and/or SGPT \< 1.5 times ULN (5 times ULN if liver metastases are present)

Renal

* Creatinine \< 1.5 times ULN OR
* Creatinine clearance \> 60 mL/min

Cardiovascular

* LVEF \> 45% by MUGA

Gastrointestinal

* No active peptic ulcer disease
* No active gastrointestinal bleeding
* No active inflammatory bowel disease

Other

* Not pregnant or nursing
* Fertile patients must use effective contraception
* No known HIV positivity
* No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer in complete remission

PRIOR CONCURRENT THERAPY:

Biologic therapy

* No concurrent filgrastim (G-CSF)

Chemotherapy

* At least 3 weeks since prior chemotherapy

Endocrine therapy

* Not specified

Radiotherapy

* At least 60 days since prior radiotherapy to the target lesion\*
* No concurrent radiotherapy NOTE: \*Lesion must have demonstrated disease progression after completion of therapy

Surgery

* At least 21 days since prior major surgery and recovered

Other

* At least 60 days since prior embolization or radiofrequency ablation to the target lesion\* NOTE: \*Lesion must have demonstrated disease progression after completion of therapy

Primary outcomes:
measure: Response rate (confirmed complete response and partial response)
Secondary outcomes:
measure: Progression-free survival at 1 and 2 years
measure: Overall survival at 1 and 2 years
measure: Toxicity
Other outcomes:
Locations:
Study officials:
affiliation: The Cleveland Clinic
name: Ernest C. Borden, MD
affiliation: University of Michigan Rogel Cancer Center
name: Rashmi Chugh, MD
affiliation: Dana-Farber Cancer Institute
name: George D. Demetri, MD
affiliation: Fox Chase Cancer Center
name: Margaret von Mehren, MD
affiliation: Tom Baker Cancer Centre - Calgary
name: Vivien H.C. Bramwell, MB, BS, PhD, FRCP
affiliation: Dana-Farber Cancer Institute
name: Karen H. Albritton, MD
References: