Trastuzumab in Treating Patients With Previously Treated, Locally Advanced, or Metastatic Cancer of the Urothelium

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Terminated

CT.gov ID

NCT00004856

Collaborator

(none)

Enrollment

Location

Arm

Study Details

Study Description

Brief Summary

Phase II trial to study the effectiveness of trastuzumab in treating patients who have previously treated, locally advanced, or metastatic cancer of the urothelium. Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells.

Condition or Disease	Intervention/Treatment	Phase
Distal Urethral Cancer Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter Proximal Urethral Cancer Recurrent Bladder Cancer Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter Recurrent Urethral Cancer Stage IV Bladder Cancer Transitional Cell Carcinoma of the Bladder Urethral Cancer Associated With Invasive Bladder Cancer	Biological: trastuzumab	Phase 2

Detailed Description

OBJECTIVES:

Determine the response rate in patients with previously treated, locally advanced or metastatic transitional cell carcinoma of the urothelium treated with trastuzumab (Herceptin).
Determine the safety of this drug in this patient population. III. Determine overall and progression-free survival of this patient population treated with this drug.

OUTLINE:

Patients receive a loading dose of trastuzumab (Herceptin) IV over 90 minutes on day 1 of week 1. For all subsequent doses, patients receive trastuzumab IV over 30 minutes weekly. Treatment may continue for more than 1 year in the absence of unacceptable toxicity or disease progression.

Patients are followed every 3 months for 1 year and then every 6 months thereafter.

Study Design

Study Type:

Interventional

Actual Enrollment :

40 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase II Trial of Trastuzumab (Herceptin; NSC #688097, IND #6667) in Patients With Previously Treated Advanced Urothelial Tract Transitional Cell Carcinoma

Study Start Date :

Jul 1, 2002

Actual Primary Completion Date :

Jul 1, 2002

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment: Herceptin Patients receive a loading dose of trastuzumab (Herceptin) IV over 90 minutes on day 1 of week 1. For all subsequent doses, patients receive trastuzumab IV over 30 minutes weekly. Treatment may continue for more than 1 year in the absence of unacceptable toxicity or disease progression.	Biological: trastuzumab Given IV Other Names: anti-c-erB-2 Herceptin MOAB HER2

Arm

Intervention/Treatment

Experimental: Treatment: Herceptin

Biological: trastuzumab

Given IV

Other Names:

anti-c-erB-2

Herceptin

MOAB HER2

Outcome Measures

Primary Outcome Measures

Objective response rate (complete or partial response) as assessed by RECIST criteria [1 year]

Secondary Outcome Measures

Toxicities as graded according to the NCI Common Toxicity Criteria [12 weeks]
Proportion of patients who are HER2 positive (3+ by IHC or FISH positive) [Baseline]
Overall survival (OS) [From date of initiation of treatment to date of death due to any cause, assessed up to 1 year]
Disease-free survival (DFS) [From date of initiation of treatment to date of progression or death due to any cause, whichever occurs first, assessed up to 1 year]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically confirmed transitional cell carcinoma (TCC) of the urothelium, including the bladder, urethra, ureter, or renal pelvis
No pure adenocarcinomas, pure squamous cell carcinomas, small cell carcinoma, or only small foci of TCC (less than 10% of tumor specimen)
Locally advanced (T4b) TCC of the bladder
Metastatic (N2 or N3 or M1)TCC of the urothelium
HER2 expression (3+) as determined by immunohistochemistry or gene amplification by fluorescent in situ hybridization
Must not be a candidate for potentially curative surgery or radiotherapy
Measurable disease
At least 1 unidimensionally measurable lesion of at least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan
The following lesions are considered nonmeasurable:
Bone lesions
Leptomeningeal disease
Ascites
Pleural/pericardial effusion
Lymphangitis cutis/pulmonis
Abdominal masses not confirmed and followed by imaging techniques
Cystic lesions
Primary bladder masses
Relapsed from or failed to achieve a complete or partial response after 1 prior systemic chemotherapy regimen for TCC, including cisplatin, carboplatin, paclitaxel, docetaxel, or gemcitabine
Prior adjuvant or neoadjuvant chemotherapy is considered 1 prior chemotherapy regimen
Prior single-agent chemotherapy as a radiosensitizer is not considered a prior systemic chemotherapy regimen
No known brain metastases
Performance status - CTC 0-2
More than 12 weeks
Absolute neutrophil count at least 1,000/mm^3
Platelet count at least 75,000/mm^3
Bilirubin no greater than 2 times upper limit of normal (ULN)
AST no greater than 2 times ULN
Creatinine clearance at least 30 mL/min
Ejection fraction at least 50% (or lower limit of normal) by echocardiogram or MUGA
No history of ongoing congestive heart failure
No active cardiac ischemia
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No other prior malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
HIV negative
No known autoimmune disease
No prior trastuzumab (Herceptin)
At least 14 days since prior radiotherapy
At least 30 days since prior chemotherapy
Prior doxorubicin allowed provided cumulative dose is no greater than 300 mg/m^2
Prior epirubicin allowed provided cumulative dose is no greater than 600 mg/m^2
No concurrent chemotherapy
No concurrent hormonal therapy except:
Steroids given for adrenal failure
Hormones administered for nondisease-related conditions (e.g., insulin for diabetes)
Intermittent dexamethasone as an antiemetic or for sensitivity reactions to study drug
No concurrent palliative radiotherapy
Prior radiotherapy allowed provided treated area is not only site of measurable disease
At least 14 days since prior surgery