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Phase II Evaluation of Trastuzumab (Herceptin), Paclitaxel, Carboplatin, and Gemcitabine in the Treatment of Advanced Urothelial Cancer


Phase 2
N/A
N/A
Not Enrolling
Both
Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter, Recurrent Bladder Cancer, Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter, Squamous Cell Carcinoma of the Bladder, Stage IV Bladder Cancer, Transitional Cell Carcinoma of the Bladder

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Trial Information

Phase II Evaluation of Trastuzumab (Herceptin), Paclitaxel, Carboplatin, and Gemcitabine in the Treatment of Advanced Urothelial Cancer


PRIMARY OBJECTIVES:

I. To assess the toxicity of the combination of Herceptin, paclitaxel, carboplatin, and
gemcitabine in patients with metastatic or locally recurrent urothelial cancers who
overexpress HER2.

SECONDARY OBJECTIVES:

I. The complete and partial response rates. II. The median and overall survival. III. To
prospectively evaluate the percentage of patients with metastatic/recurrent bladder cancer
who overexpress HER2 histologically (by immunohistochemistry and FISH) and serologically.

IV. To generate preliminary data on response to other therapy and survival for Her2 negative
patients.

OUTLINE:

Patients receive trastuzumab (Herceptin) IV over 30-90 minutes on days 1, 8, and 15;
paclitaxel IV over 3 hours and carboplatin IV over 15 minutes on day 1; and gemcitabine IV
over 30 minutes on days 1 and 8. Courses repeat every 3 weeks. Patients achieving a complete
response (CR) receive 3 courses past CR. Patients achieving a partial response or stable
disease continue on therapy until CR or disease progression or unacceptable toxicity.

Patients are followed for disease progression and survival. Patients with HER2-negative
disease are not eligible for treatment but are followed every 6 months for response and
survival.


Inclusion Criteria:



- Histologic diagnosis of urothelial carcinoma (TCC or Squamous) that is either
metastatic or locally recurrent and not curable by surgery or radiation therapy;
patients must have HER2 overexpression as documented by ANY of the following: 1. 2+
or 3+ staining by immunohistochemistry, or 2. a positive FISH score defined as > 2
with the Vysis system or > 4 with the Ventana system, or 3. an elevated serum HER2 of
> 16 ng/ml using the OSDI assay; please note:

- Tissue from either the primary or metastatic site must be tested for HER2 status
determination

- All patients must have a blood sample drawn for HER2 serologic testing

- If the available tissue is from the primary tumor and is HER2 negative and if
the serum is negative, to qualify for the study a biopsy of a metastatic site
should be done and the patient will be eligible ONLY if this demonstrates HER2
over-expression

- All sites and measurements of disease must be clearly documented in the
pre-study forms

- All prior local or adjuvant systemic therapy including the type of chemotherapy
must be clearly documented in the pre-study form Note: Patients with Her-2
negative tumors are not eligible for treatment on this protocol but their
response to other therapy and survival will also be evaluated

- Bidimensionally measurable or evaluable disease not previously radiated

- No prior systemic chemotherapy for metastatic disease; patients may have received
adjuvant chemotherapy if completed at least 6 months prior to beginning this protocol
treatment; type and number of courses of prior chemotherapy must be clearly
documented

- A performance status of 0-2 by Southwest Oncology Group criteria and a life
expectancy of greater than 12 weeks

- Serum creatinine =< 2.0 mg%

- Granulocyte count >= 1,500/mm^3

- Platelet >= 100,000/mm^3

- Total bilirubin =< 1.5 mg/dl

- No significant cardiac disease and must have adequate cardiac function (ejection
fraction >= 50% or higher than the lower limit of institutional normal) as determined
by a MUGA scan or 2-D echocardiogram within 4 weeks from registration, and no
evidence of symptomatic coronary artery disease (baseline EKG must show no active
ischemia); patients must not have history of congestive heart failure

- If patients have received prior radiation therapy, disease must be present outside of
radiated fields and at least 4 weeks must have elapsed since discontinuation of that
therapy; the nadirs of RT leukopenia and thrombocytopenia must be surpassed with
evidence of hematologic recovery

- No prior malignancy is allowed, except for adequately treated basal cell (or squamous
cell) skin cancer, in situ carcinoma of any site or other cancer for which the
patient is currently disease free

- Patient may not have unresolved bacterial infection

- Pregnant or lactating women may not participate; this is to avoid potential harm
since the effects of study drugs on the fetus or the nursing infant are not known;
women/men of reproductive potential may not participate unless they have agreed to
use an effective contraceptive method

- HIV -positive patients may not participate; this is to avoid additional complications
that immune suppression and HIV infection may cause due to the intense nature of the
chemotherapy in this trial

- Timing guidelines for pre-study labs (excluding HER2 determination) and measurements;

- To be completed within 14 days prior to registration; pre-study labs required
for determination of eligibility

- To be completed within 28 days prior to registration: x-rays, scans or physical
examination used for tumor

- All patients must be informed of the investigational nature of this study and must
sign an informed consent in accordance with institutional and federal guidelines

- All patients must be registered with the UM Cancer Center Clinical Trials Office at
734-647-8174 (Joanne Goodson) prior to instituting therapy

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Cardiac toxicity rate of this combination using MUGA or 2D ECHO

Outcome Time Frame:

Up to 7 years

Safety Issue:

Yes

Principal Investigator

Maha Hussain

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Michigan University Hospital

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-03187

NCT ID:

NCT00005831

Start Date:

March 2000

Completion Date:

Related Keywords:

  • Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter
  • Recurrent Bladder Cancer
  • Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter
  • Squamous Cell Carcinoma of the Bladder
  • Stage IV Bladder Cancer
  • Transitional Cell Carcinoma of the Bladder
  • Urinary Bladder Neoplasms
  • Carcinoma
  • Carcinoma, Squamous Cell
  • Carcinoma, Transitional Cell
  • Kidney Neoplasms
  • Ureteral Neoplasms
  • Urologic Neoplasms

Name

Location

University of Michigan University HospitalAnn Arbor, Michigan  48109