Trastuzumab and Combination Chemotherapy in Treating Patients With Locally Recurrent or Metastatic Urinary Tract Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00005831
First received: June 2, 2000
Last updated: January 11, 2013
Last verified: January 2013
  Purpose

Phase II trial to study the effectiveness of combining trastuzumab with combination chemotherapy in treating patients who have locally recurrent or metastatic urinary tract cancer. Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining monoclonal antibody therapy with combination chemotherapy may kill more tumor cells


Condition Intervention Phase
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
Biological: trastuzumab
Drug: paclitaxel
Drug: carboplatin
Drug: gemcitabine hydrochloride
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Evaluation of Trastuzumab (Herceptin), Paclitaxel, Carboplatin, and Gemcitabine in the Treatment of Advanced Urothelial Cancer

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Cardiac toxicity rate of this combination using MUGA or 2D ECHO [ Time Frame: Up to 7 years ] [ Designated as safety issue: Yes ]
  • Response rate [ Time Frame: Up to 7 years ] [ Designated as safety issue: No ]
    The response rate of this regimen will be estimated with a standard error no greater than 7.9%.


Secondary Outcome Measures:
  • Time to disease progression [ Time Frame: Up to 7 years ] [ Designated as safety issue: No ]
    Kaplan-Meier method will be used for the analysis and graphic presentation of this data.

  • Survival duration [ Time Frame: Up to 7 years ] [ Designated as safety issue: No ]
    Kaplan-Meier method will be used for the analysis and graphic presentation of this data.


Estimated Enrollment: 40
Study Start Date: March 2000
Primary Completion Date: August 2004 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (trastuzumab, combination chemotherapy)
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.
Biological: trastuzumab
Given IV
Other Names:
  • anti-c-erB-2
  • Herceptin
  • MOAB HER2
Drug: paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • TAX
  • Taxol
Drug: carboplatin
Given IV
Other Names:
  • Carboplat
  • CBDCA
  • JM-8
  • Paraplat
  • Paraplatin
Drug: gemcitabine hydrochloride
Given IV
Other Names:
  • dFdC
  • difluorodeoxycytidine hydrochloride
  • gemcitabine
  • Gemzar
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

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.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00005831

Locations
United States, Michigan
University of Michigan University Hospital
Ann Arbor, Michigan, United States, 48109
Sponsors and Collaborators
Investigators
Principal Investigator: Maha Hussain University of Michigan University Hospital
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00005831     History of Changes
Other Study ID Numbers: NCI-2012-03187, UMCC-9955, U01CA062487, N01CM17101, CDR0000067845
Study First Received: June 2, 2000
Last Updated: January 11, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Urinary Bladder Neoplasms
Carcinoma
Carcinoma, Squamous Cell
Carcinoma, Transitional Cell
Kidney Neoplasms
Ureteral Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Urinary Bladder Diseases
Urologic Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Squamous Cell
Kidney Diseases
Ureteral Diseases
Gemcitabine
Trastuzumab
Carboplatin
Paclitaxel
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors

ClinicalTrials.gov processed this record on July 20, 2014