Clinical trial NCT00004163: Trastuzumab in Treating Patients With Advanced Salivary Gland Cancer
Official title: Herceptin In Patients With Advanced or Metastatic Salivary Gland Carcinomas
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Head and Neck Cancer
Keywords: stage III salivary gland cancer
stage IV salivary gland cancer
recurrent salivary gland cancer
salivary gland squamous cell carcinoma
salivary gland acinic cell tumor
low-grade salivary gland mucoepidermoid carcinoma
high-grade salivary gland mucoepidermoid carcinoma
salivary gland adenocarcinoma
salivary gland poorly differentiated carcinoma
salivary gland malignant mixed cell type tumor
salivary gland adenoid cystic carcinoma
Lead sponsor: Dana-Farber Cancer Institute
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: Genentech, Inc.
First posted: 2004-03-15
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Monoclonal antibodies, such as trastuzumab, can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells.

PURPOSE: Phase II trial to study the effectiveness of trastuzumab in treating patients who have advanced salivary gland cancer.

Detailed description: Due to the age of this study upon transfer from the NCI to DFCI, data was not accessible to find the exact primary completion date (PCD) or study completion date (SCD). The September 2001 date used for both is based on known enrollment dates and an estimate on median time to progression (TTP) in the setting of this clinical trial. Since participants were treated indefinitely until progression, TTP is deemed to reflect generally the time on treatment for evaluation of the primary response outcome. Furthermore, patients were followed for progression to estimate TTP, a secondary outcome measure.

OBJECTIVES: I. Determine the response rate to trastuzumab in patients with advanced or metastatic salivary gland cancer. II. Determine the time to progression in these patients after this regimen. III. Determine the toxicity of trastuzumab in these patients.

OUTLINE: Patients are stratified according to histology: intercalated duct (adenoid cystic carcinoma, acinic cell carcinoma, malignant mixed tumor, polymorphous low grade adenocarcinoma, undifferentiated carcinoma, adenocarcinoma) vs excretory duct (squamous cell carcinoma, mucoepidermoid carcinoma).

PROJECTED ACCRUAL: A total of 50 patients (25 per stratum) will be accrued for this study.

Eligibility criteria: Inclusion Criteria

* Histologic diagnosis of any of the following malignancies originating from salivary tissue: adenoid cystic carcinoma, mucoepidermoid carcinoma, acinic cell carcinoma, malignant mixed tumor, polymorphous low grade adenocarcinoma, undifferentiated carcinoma, squamous cell carcinoma, adenocarcinoma.
* Her2/neu determination: Patients must have overexpression of the Her2/neu protein in the tumor documented by the Dako polyclonal rabbit anti-Her2 antisera assay.

Overexpression may be documented by staining of the original paraffin embedded tumor from the time of diagnosis or from material obtained at the time of locoregional or distant recurrence.

Overexpression of HER2/neu will be per the Dako Herceptest guidelines. A Score of 2+ or 3+ will be defined as overexpression. All slides will be reviewed by members of the departments of pathology at either the Brigham and Women's Hospital or the Beth Israel Hospital in Boston.

* Patients must be incurable on the basis of unresectable local or distant disease as determined by the patient's surgeon.
* Patients must have an ECOG performance status of 0 to 1.
* Patients must have at least uni-dimensionally measurable disease documented within one month of initiation of treatment. Measurement may be by physical exam or radiologically. Attempts should be made to photo document all tumor sites assessed by physical examination with a metric ruler within the photo for measurement confirmation.
* Patients must be willing and able to go through the process of informed consent.
* Patients must have a life expectancy exceeding 3 months.
* Patients must be at least 18 years old.
* Patients must have adequate organ function as defined by the following tests to be performed within 14 days of therapy initiation:

  * Absolute neutrophil count \> 1999 cells x 10 61L
  * Platelet count \> 99,999 cells x 106/L
  * Hemoglobin \>8.5 gm/di or HCT \> 25%
  * Serum creatinine \< 1.5 x institutional upper limits of normal (ULN) or creatinine clearance measured by 24 hour urine collection as at least 50% of institutional lower limit of normal.
  * Total bilirubin \<2 x institutional ULN
  * AST (SGOT) \< 2 x institutional ULN \*
* If from documented liver involvement with cancer, may be up to \< 5 x institutional ULN Alkaline Phosphatase \< 5 x institutional ULN \*
* If from documented bone or liver involvement with cancer, no upper limit restriction.
* Baseline determination of normal left ventricular ejection fraction as evidenced MUGA or echocardiogram.

Exclusion Criteria:

* Patients must not have received more than two regimens of cytotoxic chemotherapy for salivary gland cancer. Previous immunologic, hormonal, homeopathic, natural, or alternative medicine therapies are acceptable provided treatment ended greater than 28 days prior to protocol therapy.
* Patients must not receive any form (including radiotherapeutic, immunologic, hormonal, homeopathic, natural, or alternative medicine) of anti-neoplastic therapy other than Herceptin while participating in this study.
* Patients must not have a history of any non-salivary invasive neoplasm within three years of trial entry, excepting curatively treated non-melanoma skin cancer and cervical cancer.
* Pregnant and breast feeding women are not eligible for this study. No pregnancy test is required. Women of childbearing potential must be counseled on the use of effective birth control prior to participation in this study.
* Patients with significant active illness (e.g. congestive heart failure, COPD, uncontrolled diabetes, AIDS, previous MI, cardiomyopathies, history of uncontrolled arrhythmias) are not eligible for this study.
* Patients who have received anthracyclines (e.g. doxorubicin, daunorubicin, epirubicin) are eligible but must have a baseline MUGA scan documenting normal cardiac contractility (at or above the normal institutional limit) within one month of trial enrollment. The upper limit of doxorubicin exposure should be no more than 360mg1m2

Primary outcomes:
measure: Response Rate
timeFrame: 2 years
Secondary outcomes:
measure: Time to Progression
timeFrame: 2 years
measure: Toxicity
timeFrame: 2 years
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale-New Haven Hospital
state: Connecticut
city: Port Saint Lucie
country: United States
facility: Hematology/Oncology Associates
state: Florida
city: Boston
country: United States
facility: Massachusetts General Hospital Cancer Center
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Hyannis
country: United States
facility: Cape Cod Health Care
state: Massachusetts
city: Nantucket
country: United States
facility: Nantucket Cottage Hospital
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University Barnard Cancer Center
state: Missouri
city: Binghamton
country: United States
facility: Lourdes Regional Cancer Center
state: New York
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Houston
country: United States
facility: University of Texas - MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Marshall R. Posner, MD
role: STUDY_CHAIR
References: