Paclitaxel and Radiation Therapy With or Without Trastuzumab in Treating Patients Who Have Undergone Surgery for Bladder Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00238420
First received: October 12, 2005
Last updated: April 14, 2014
Last verified: March 2014
  Purpose

This phase I/II trial is studying the side effects of giving paclitaxel together with radiation therapy with or without trastuzumab and to see how well it works to kill any remaining tumor cells in patients who have undergone surgery for bladder cancer. Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Paclitaxel may also make tumor cells more sensitive to radiation therapy. Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving paclitaxel together with radiation therapy and trastuzumab may kill more tumor cells. Giving these treatments after surgery may kill any remaining tumor cells.


Condition Intervention Phase
Stage I Bladder Cancer
Stage II Bladder Cancer
Stage III Bladder Cancer
Transitional Cell Carcinoma of the Bladder
Drug: paclitaxel
Biological: trastuzumab
Radiation: radiation therapy
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Trial of a Combination of Paclitaxel and Trastuzumab With Daily Irradiation or Paclitaxel Alone With Daily Irradiation Following Transurethral Surgery for Non-Cystectomy Candidates With Muscle-Invasive Bladder Cancer

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Acute treatment-related toxicity [ Time Frame: At least 90 days ] [ Designated as safety issue: Yes ]
    For each patient group, the number of patients will be tabulated by the type and grade of toxicity.


Secondary Outcome Measures:
  • Treatment completion [ Time Frame: Up to at least 5 years ] [ Designated as safety issue: No ]
  • Complete response to treatment [ Time Frame: At 12 weeks ] [ Designated as safety issue: No ]
  • Disease-free survival [ Time Frame: From the date of treatment started to the date of documentation of progression or until the date of death, assessed up to at least 5 years ] [ Designated as safety issue: No ]
    Calculated using the Kaplan-Meier method.

  • Overall survival [ Time Frame: From the date of treatment started to the date of the failure event, assessed up to at least 5 years ] [ Designated as safety issue: No ]
    Calculated using the Kaplan-Meier method.


Enrollment: 74
Study Start Date: July 2005
Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group I (paclitaxel, trastuzumab, radiation therapy)
Patients receive paclitaxel IV over 1 hour on days 1, 8, 15, 22, 29, 36, and 43 and trastuzumab IV over 90 minutes on day 1 and then over 30 minutes on days 8, 15, 22, 29, 36, and 43. Patients also undergo radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, 43-47, and 50. Treatment continues in the absence of disease progression or unacceptable toxicity.
Drug: paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • TAX
  • Taxol
Biological: trastuzumab
Given IV
Other Names:
  • anti-c-erB-2
  • Herceptin
  • MOAB HER2
Radiation: radiation therapy
Undergo radiation therapy
Other Names:
  • irradiation
  • radiotherapy
  • therapy, radiation
Experimental: Group II (paclitaxel, radiation therapy)
Patients receive paclitaxel and undergo radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, 43-47, and 50.
Drug: paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • TAX
  • Taxol
Radiation: radiation therapy
Undergo radiation therapy
Other Names:
  • irradiation
  • radiotherapy
  • therapy, radiation

Detailed Description:

PRIMARY OBJECTIVE:

I. To determine the acute toxicity (=< 90 days from protocol treatment start) from chemoradiotherapy including paclitaxel +/- trastuzumab and irradiation in non-cystectomy patients with or without her2/neu overexpression.

SECONDARY OBJECTIVES:

I. To determine the ability of patients with bladder cancer who are non-cystectomy candidates to complete this treatment program.

II. To evaluate the efficacy of this treatment program in achieving a complete response of the primary tumor.

III. To measure the 5-year disease-free and overall survival of patients with bladder cancer treated with TURB followed by chemoradiotherapy.

IV. To estimate the value of tumor and/or serum biomarkers as predictors of initial tumor response and recurrence-free survival.

OUTLINE: This is a non-randomized, multicenter study. Patients are assigned to 1 of 2 treatment groups according to HER2/neu status (HER2/neu 2+ or 3+ staining [group 1] vs HER2/neu 0 or 1+ staining [group 2]).

GROUP I: Patients receive paclitaxel intravenously (IV) over 1 hour on days 1, 8, 15, 22, 29, 36, and 43 and trastuzumab (Herceptin®) IV over 90 minutes on day 1 and then over 30 minutes on days 8, 15, 22, 29, 36, and 43. Patients also undergo radiotherapy once daily on days 1-5, 8-12, 15-19, 22-26, 29-33, 36-40, 43-47, and 50. Treatment continues in the absence of disease progression or unacceptable toxicity.

GROUP II: Patients receive paclitaxel and undergo radiotherapy as in group 1.

After completion of study treatment, patients are followed at 4-5 weeks, every 3 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically confirmed primary transitional cell carcinoma (TCC) of the bladder

    • Histologic evidence of muscularis propria invasion
  • Meets 1 of the following stage criteria:

    • Stage T2-4a; NX, N0, or N1; and M0 disease
    • Clinical stage T1, grade 3/3 disease AND requires definitive local therapy
  • Tumor involvement of the prostatic urethra allowed provided the following criteria are met:

    • Tumor was visibly completely resected
    • No evidence of stromal invasion of the prostate
    • No evidence of distant metastases by chest x-ray (or chest CT scan) within 8 weeks prior to registration
    • No evidence of distant metastases by abdominal/pelvic CT scan (or MRI scan) within 8 weeks prior to registration
  • Has undergone transurethral bladder resection (as thorough as is judged safely possible) within the past 3-8 weeks, including bimanual examination with tumor mapping
  • Sufficient tumor tissue available for HER2/neu analysis
  • Not a candidate for radical cystectomy
  • Performance status - Zubrod 0-2
  • Absolute neutrophil count >= 1,800/mm^3
  • Platelet count >= 100,000/mm^3
  • Hemoglobin >= 8.0 g/dL (transfusion or other intervention allowed)
  • Bilirubin < 2.0 mg/dL
  • SGOT and SGPT < 2.5 times upper limit of normal
  • No hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
  • Creatinine =< 3.0 mg/dL
  • LVEF >= 40% by MUGA scan or echocardiogram
  • No unstable angina and/or congestive heart failure requiring hospitalization within the past 6 months
  • No transmural myocardial infarction within the past 6 months
  • Not pregnant or nursing
  • No nursing for 6 months after completion of study treatment (for patients receiving trastuzumab [Herceptin®])
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 6 months after completion of study treatment
  • Able to tolerate systemic chemotherapy and pelvic radiotherapy
  • No other invasive malignancy within the past 3 years except nonmelanoma skin cancer
  • No history of allergic reaction to study drugs
  • No history of inflammatory bowel disease
  • No acute bacterial or fungal infection requiring IV antibiotics
  • No AIDS
  • No other severe active comorbidity
  • No prior systemic chemotherapy with anthracyclines or taxanes
  • No prior systemic chemotherapy for TCC
  • No prior pelvic radiotherapy
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00238420

  Show 153 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: M. Dror Michaelson Radiation Therapy Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00238420     History of Changes
Other Study ID Numbers: NCI-2009-00730, NCI-2009-00730, RTOG-0524, CDR0000440988, RTOG 0524, RTOG-0524, U10CA021661
Study First Received: October 12, 2005
Last Updated: April 14, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Urinary Bladder Neoplasms
Carcinoma
Carcinoma, Transitional Cell
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Urinary Bladder Diseases
Urologic Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Paclitaxel
Trastuzumab
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 17, 2014