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

National Cancer Institute (NCI)

Status and phase

Terminated

Phase 2

Conditions

Urethral Cancer Associated With Invasive Bladder Cancer

Proximal Urethral Cancer

Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter

Transitional Cell Carcinoma of the Bladder

Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter

Recurrent Bladder Cancer

Stage IV Bladder Cancer

Distal Urethral Cancer

Recurrent Urethral Cancer

Treatments

Biological: trastuzumab

Study type

Interventional

Funder types

NIH

Identifiers

NCT00004856

CALGB 90101

UCSF-99535

U10CA031946 (U.S. NIH Grant/Contract)

NCI-T99-0108

NCI-2011-02046

CDR0000067476

CALGB-90101

Details and patient eligibility

About

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.

Full description

OBJECTIVES:

I. Determine the response rate in patients with previously treated, locally advanced or metastatic transitional cell carcinoma of the urothelium treated with trastuzumab (Herceptin).

II. 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.

Enrollment

40 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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