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

Sponsors and Collaborators:	Radiation Therapy Oncology Group National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00238420

Purpose

RATIONALE: 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.

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.

Condition	Intervention	Phase
Bladder Cancer	Biological: trastuzumab Drug: paclitaxel Radiation: radiation therapy	Phase I Phase II

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized
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:

Genetics Home Reference related topics: bladder cancer

MedlinePlus related topics: Bladder Cancer Cancer Radiation Therapy Surgery

Drug Information available for: Paclitaxel Trastuzumab

U.S. FDA Resources

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

Primary Outcome Measures:

Safety during weekly treatment [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Complete response rate by cystoscopy at 12 weeks [ Designated as safety issue: No ]

Estimated Enrollment:	88
Study Start Date:	July 2005
Estimated Primary Completion Date:	July 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Group 1: Experimental Patients receive paclitaxel 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.	Biological: trastuzumab Given IV Drug: paclitaxel Given IV Radiation: radiation therapy Given once daily
Group 2: Experimental 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 Radiation: radiation therapy Given once daily

Arms

Assigned Interventions

Group 1: Experimental

Patients receive paclitaxel 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.

Biological: trastuzumab

Given IV

Drug: paclitaxel

Given IV

Radiation: radiation therapy

Given once daily

Group 2: Experimental

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

Radiation: radiation therapy

Given once daily

Detailed Description:

OBJECTIVES:

Primary

Determine the acute toxicity of paclitaxel and radiotherapy with or without trastuzumab (Herceptin®) in patients who have undergone prior transurethral bladder resection for muscle-invasive transitional cell carcinoma of the bladder.

Secondary

Determine the ability of these patients to complete these regimens.
Determine the efficacy of these regimens, in terms of achieving a complete response of the primary tumor, in these patients.
Determine the 5-year disease-free and overall survival of patients treated with these regimens.
Determine the value of tumor and/or serum biomarkers as predictors of initial tumor response and recurrence-free survival of patients treated with these regimens.

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 1: Patients receive paclitaxel 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 2: 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.

PROJECTED ACCRUAL: A total of 88 patients (44 per treatment group) will be accrued for this study within approximately 3 years.

Eligibility

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

Criteria

DISEASE CHARACTERISTICS:

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 CT scan AND abdominal/pelvic CT scan
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

PATIENT CHARACTERISTICS:

Age

18 and over

Performance status

Zubrod 0-2

Life expectancy

Not specified

Hematopoietic

Absolute neutrophil count ≥ 1,800/mm^3
Platelet count ≥ 100,000/mm^3
Hemoglobin ≥ 8.0 g/dL (transfusion or other intervention allowed)

Hepatic

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

Renal

Creatinine ≤ 3.0 mg/dL

Cardiovascular

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

Other

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

PRIOR CONCURRENT THERAPY:

Biologic therapy

Not specified

Chemotherapy

No prior systemic chemotherapy with anthracyclines or taxanes
No prior systemic chemotherapy for TCC

Endocrine therapy

Not specified

Radiotherapy

No prior pelvic radiotherapy

Surgery

See Disease Characteristics

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00238420

Locations

United States, California
Auburn Radiation Oncology	Recruiting
Auburn, California, United States, 95603
Contact: Christopher Jones, MD 916-646-6600
Mercy Cancer Center at Mercy San Juan Medical Center	Recruiting
Carmichael, California, United States, 95608
Contact: Christopher Jones, MD 916-646-6600
Mercy General Hospital	Recruiting
Sacramento, California, United States, 95819
Contact: Christopher Jones, MD 916-646-6600
Solano Radiation Oncology Center	Recruiting
Vacaville, California, United States, 95687
Contact: Christopher Jones, MD 916-646-6600
Radiation Oncology Centers - Cameron Park	Recruiting
Cameron Park, California, United States, 95682
Contact: Christopher Jones, MD 916-646-6600
Radiological Associates of Sacramento Medical Group, Incorporated	Recruiting
Sacramento, California, United States, 95815
Contact: Christopher Jones, MD 916-646-6600
Radiation Oncology Center - Roseville	Recruiting
Roseville, California, United States, 95661
Contact: Christopher Jones, MD 916-646-6600

Sponsors and Collaborators

Radiation Therapy Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:	M. Dror Michaelson, MD, PhD	Massachusetts General Hospital
Investigator:	Alan Pollack, MD, PhD	Fox Chase Cancer Center
Investigator:	Douglas M. Dahl, MD	Massachusetts General Hospital

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Featured trial article This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Radiation Therapy Oncology Group ( Walter John Curran, Jr )
Study ID Numbers:	CDR0000440988, RTOG-0524
Study First Received:	October 12, 2005
Last Updated:	September 5, 2009
ClinicalTrials.gov Identifier:	NCT00238420 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

stage I bladder cancer
transitional cell carcinoma of the bladder
stage II bladder cancer
stage III bladder cancer

Study placed in the following topic categories:

Urinary Tract Neoplasm
Cystocele
Urinary Bladder Diseases
Urinary Bladder Neoplasms
Urogenital Neoplasms
Antimitotic Agents
Carcinoma, Transitional Cell
Urologic Neoplasms

Carcinoma
Urologic Diseases
Paclitaxel
Tubulin Modulators
Trastuzumab
Bladder Neoplasm
Antineoplastic Agents, Phytogenic
Transitional Cell Carcinoma

Additional relevant MeSH terms:

Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Urinary Bladder Diseases
Mitosis Modulators
Urinary Bladder Neoplasms
Urogenital Neoplasms
Antimitotic Agents
Urologic Neoplasms
Pharmacologic Actions

Neoplasms
Neoplasms by Site
Urologic Diseases
Paclitaxel
Therapeutic Uses
Tubulin Modulators
Trastuzumab
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on September 11, 2009