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

Bladder Urothelial Carcinoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00238420
• Other study ID #: NCI-2009-00730
• Secondary ID: NCI-2009-00730RT
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: July 26, 2005
• Est. completion date: May 20, 2022

Study information

• Verified date: May 2022
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

PRIMARY OBJECTIVES:

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 transurethral resection of the bladder 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: May 20, 2022
• Est. primary completion date: February 5, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

• Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) < 2.5 times upper limit of normal

• No hepatic insufficiency resulting in clinical jaundice and/or coagulation defects

• Creatinine =< 3.0 mg/dL

• Left ventricular ejection fraction (LVEF) >= 40% by multigated acquisition scan (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

Related Conditions & MeSH terms

• Bladder Urothelial Carcinoma
• Stage I Bladder Cancer AJCC v6 and v7
• Stage II Bladder Cancer AJCC v6 and v7
• Stage III Bladder Cancer AJCC v6 and v7
• Urinary Bladder Neoplasms

Intervention

Drug:
• Paclitaxel
Given IV

Radiation:
• Radiation Therapy
Undergo radiation therapy

Biological:
• Trastuzumab
Given IV

Locations

Country	Name	City	State
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	London Regional Cancer Program	London	Ontario
Canada	McGill University Department of Oncology	Montreal	Quebec
Canada	Atlantic Health Sciences Corporation-Saint John Regional Hospital	Saint John	New Brunswick
United States	Cleveland Clinic Akron General	Akron	Ohio
United States	Summa Health System - Akron Campus	Akron	Ohio
United States	McFarland Clinic PC - Ames	Ames	Iowa
United States	Providence Alaska Medical Center	Anchorage	Alaska
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Sutter Cancer Centers Radiation Oncology Services-Auburn	Auburn	California
United States	Rush - Copley Medical Center	Aurora	Illinois
United States	Summa Health System - Barberton Campus	Barberton	Ohio
United States	Billings Clinic Cancer Center	Billings	Montana
United States	Montana Cancer Consortium NCORP	Billings	Montana
United States	Northern Rockies Radiation Oncology Center	Billings	Montana
United States	Mid Dakota Clinic	Bismarck	North Dakota
United States	Saint Alexius Medical Center	Bismarck	North Dakota
United States	Sanford Bismarck Medical Center	Bismarck	North Dakota
United States	Illinois CancerCare-Bloomington	Bloomington	Illinois
United States	Saint Joseph Medical Center	Bloomington	Illinois
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Boston Medical Center	Boston	Massachusetts
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Bozeman Deaconess Hospital	Bozeman	Montana
United States	Providence Saint Joseph Medical Center/Disney Family Cancer Center	Burbank	California
United States	Cooper Hospital University Medical Center	Camden	New Jersey
United States	Sutter Cancer Centers Radiation Oncology Services-Cameron Park	Cameron Park	California
United States	Cleveland Clinic Mercy Hospital	Canton	Ohio
United States	Graham Hospital Association	Canton	Illinois
United States	Illinois CancerCare-Canton	Canton	Illinois
United States	Mercy San Juan Medical Center	Carmichael	California
United States	Illinois CancerCare-Carthage	Carthage	Illinois
United States	Memorial Hospital	Carthage	Illinois
United States	Sandra L Maxwell Cancer Center	Cedar City	Utah
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Novant Health Presbyterian Medical Center	Charlotte	North Carolina
United States	Clackamas Radiation Oncology Center	Clackamas	Oregon
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	MetroHealth Medical Center	Cleveland	Ohio
United States	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado
United States	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas
United States	Danville Regional Medical Center	Danville	Virginia
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	Heartland Cancer Research NCORP	Decatur	Illinois
United States	Iowa Lutheran Hospital	Des Moines	Iowa
United States	Iowa Methodist Medical Center	Des Moines	Iowa
United States	Iowa-Wide Oncology Research Coalition NCORP	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates-Des Moines	Des Moines	Iowa
United States	Medical Oncology and Hematology Associates-Laurel	Des Moines	Iowa
United States	Mercy Capitol	Des Moines	Iowa
United States	Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Cancer Center of Kansas - Dodge City	Dodge City	Kansas
United States	Delaware County Memorial Hospital	Drexel Hill	Pennsylvania
United States	Northeast Radiation Oncology Center	Dunmore	Pennsylvania
United States	Cancer Center of Kansas - El Dorado	El Dorado	Kansas
United States	Christiana Care - Union Hospital	Elkton	Maryland
United States	Eureka Hospital	Eureka	Illinois
United States	Illinois CancerCare-Eureka	Eureka	Illinois
United States	Saint Anne's Hospital	Fall River	Massachusetts
United States	Saint Francis Hospital	Federal Way	Washington
United States	Holy Cross Hospital	Fort Lauderdale	Florida
United States	Parkview Hospital Randallia	Fort Wayne	Indiana
United States	Radiation Oncology Associates PC	Fort Wayne	Indiana
United States	Fox Chase Cancer Center Buckingham	Furlong	Pennsylvania
United States	Galesburg Cottage Hospital	Galesburg	Illinois
United States	Illinois CancerCare-Galesburg	Galesburg	Illinois
United States	Western Illinois Cancer Treatment Center	Galesburg	Illinois
United States	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana
United States	Berdeaux, Donald MD (UIA Investigator)	Great Falls	Montana
United States	Great Falls Clinic	Great Falls	Montana
United States	Illinois CancerCare-Havana	Havana	Illinois
United States	Mason District Hospital	Havana	Illinois
United States	Hopedale Medical Complex - Hospital	Hopedale	Illinois
United States	University of Florida Health Science Center - Jacksonville	Jacksonville	Florida
United States	Duly Health and Care Joliet	Joliet	Illinois
United States	Jupiter Medical Center	Jupiter	Florida
United States	Borgess Medical Center	Kalamazoo	Michigan
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	University of Kansas Cancer Center	Kansas City	Kansas
United States	Cheshire Medical Center-Dartmouth-Hitchcock Keene	Keene	New Hampshire
United States	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois
United States	Kewanee Hospital	Kewanee	Illinois
United States	Vidant Oncology-Kinston	Kinston	North Carolina
United States	EvergreenHealth Medical Center	Kirkland	Washington
United States	Nevada Cancer Institute-Summerlin Campus	Las Vegas	Nevada
United States	Nevada Cancer Research Foundation NCORP	Las Vegas	Nevada
United States	University Medical Center of Southern Nevada	Las Vegas	Nevada
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	Beebe Medical Center	Lewes	Delaware
United States	University of Kentucky/Markey Cancer Center	Lexington	Kentucky
United States	Southwest Medical Center	Liberal	Kansas
United States	Logan Regional Hospital	Logan	Utah
United States	Illinois CancerCare-Macomb	Macomb	Illinois
United States	Mcdonough District Hospital	Macomb	Illinois
United States	Riddle Memorial Hospital	Media	Pennsylvania
United States	University of Miami Miller School of Medicine-Sylvester Cancer Center	Miami	Florida
United States	Mount Sinai Medical Center	Miami Beach	Florida
United States	Franciscan Saint Anthony Health-Michigan City	Michigan City	Indiana
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Providence Milwaukie Hospital	Milwaukie	Oregon
United States	Mobile Infirmary Medical Center	Mobile	Alabama
United States	Holy Family Medical Center	Monmouth	Illinois
United States	Illinois CancerCare-Monmouth	Monmouth	Illinois
United States	Virtua Memorial	Mount Holly	New Jersey
United States	Cottonwood Hospital Medical Center	Murray	Utah
United States	Intermountain Medical Center	Murray	Utah
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital	New Brunswick	New Jersey
United States	Christiana Care Health System-Christiana Hospital	Newark	Delaware
United States	Bromenn Regional Medical Center	Normal	Illinois
United States	Carle Cancer Institute Normal	Normal	Illinois
United States	Illinois CancerCare-Community Cancer Center	Normal	Illinois
United States	McKay-Dee Hospital Center	Ogden	Utah
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Orlando Health Cancer Institute	Orlando	Florida
United States	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois
United States	Ottawa Regional Hospital and Healthcare Center	Ottawa	Illinois
United States	Bay Medical Center	Panama City	Florida
United States	Singing River Hospital	Pascagoula	Mississippi
United States	Illinois CancerCare-Pekin	Pekin	Illinois
United States	OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center	Pekin	Illinois
United States	Pekin Hospital	Pekin	Illinois
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	OSF Saint Francis Medical Center	Peoria	Illinois
United States	OSF Saint Francis Radiation Oncology at Peoria Cancer Center	Peoria	Illinois
United States	Proctor Hospital	Peoria	Illinois
United States	Illinois CancerCare-Peru	Peru	Illinois
United States	Illinois Valley Hospital	Peru	Illinois
United States	Valley Radiation Oncology	Peru	Illinois
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	Providence Portland Medical Center	Portland	Oregon
United States	Providence Saint Vincent Medical Center	Portland	Oregon
United States	Hudson Valley Oncology Associates	Poughkeepsie	New York
United States	Illinois CancerCare-Princeton	Princeton	Illinois
United States	Perry Memorial Hospital	Princeton	Illinois
United States	Utah Valley Regional Medical Center	Provo	Utah
United States	The Reverend Roger Patrick Dorcy Cancer Center at Saint Mary-Corwin Medical Center	Pueblo	Colorado
United States	MultiCare Good Samaritan Hospital	Puyallup	Washington
United States	Valley Medical Center	Renton	Washington
United States	Sutter Cancer Centers Radiation Oncology Services-Roseville	Roseville	California
United States	Mercy General Hospital Radiation Oncology Center	Sacramento	California
United States	Sutter Medical Center Sacramento	Sacramento	California
United States	Saint George Regional Medical Center	Saint George	Utah
United States	Norris Cotton Cancer Center-North	Saint Johnsbury	Vermont
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	UH Seidman Cancer Center at Salem Regional Medical Center	Salem	Ohio
United States	Cancer Center of Kansas - Salina	Salina	Kansas
United States	LDS Hospital	Salt Lake City	Utah
United States	Utah Cancer Specialists-Salt Lake City	Salt Lake City	Utah
United States	Virginia Mason Medical Center	Seattle	Washington
United States	Welch Cancer Center	Sheridan	Wyoming
United States	Mercy Medical Center-Sioux City	Sioux City	Iowa
United States	Saint Luke's Regional Medical Center	Sioux City	Iowa
United States	Siouxland Regional Cancer Center	Sioux City	Iowa
United States	Illinois CancerCare-Spring Valley	Spring Valley	Illinois
United States	Saint Margaret's Hospital	Spring Valley	Illinois
United States	Memorial Medical Center	Springfield	Illinois
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	Springfield Regional Medical Center	Springfield	Ohio
United States	MultiCare Tacoma General Hospital	Tacoma	Washington
United States	Northwest NCI Community Oncology Research Program	Tacoma	Washington
United States	Saint Joseph Medical Center	Tacoma	Washington
United States	Carle Cancer Center	Urbana	Illinois
United States	Sutter Cancer Centers Radiation Oncology Services-Vacaville	Vacaville	California
United States	Compass Oncology Vancouver	Vancouver	Washington
United States	PeaceHealth Southwest Medical Center	Vancouver	Washington
United States	Inspira Medical Center Vineland	Vineland	New Jersey
United States	MedStar Georgetown University Hospital	Washington	District of Columbia
United States	Cancer Center of Kansas - Wellington	Wellington	Kansas
United States	Ascension Via Christi Hospitals Wichita	Wichita	Kansas
United States	Associates In Womens Health	Wichita	Kansas
United States	Cancer Center of Kansas - Wichita	Wichita	Kansas
United States	Cancer Center of Kansas-Wichita Medical Arts Tower	Wichita	Kansas
United States	Wesley Medical Center	Wichita	Kansas
United States	Wichita NCI Community Oncology Research Program	Wichita	Kansas
United States	Saint Francis Hospital - Wilmington	Wilmington	Delaware
United States	Cancer Center of Kansas - Winfield	Winfield	Kansas
United States	Cancer Treatment Center	Wooster	Ohio
United States	Lankenau Medical Center	Wynnewood	Pennsylvania
United States	Main Line Health NCORP	Wynnewood	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)	Radiation Therapy Oncology Group

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Acute Treatment-related Toxicity	In each group, the number of patients was tabulated by type and grade (gr) of treatment-related toxicity (CTCAE v3.0). Only the following types of toxicity within 90 days of treatment start were considered: = gr4 neutropenia, = gr4 febrile neutropenia, = gr3 diarrhea, = gr3 nausea/vomiting, = gr3 thrombocytopenia, = gr3 renal, pulmonary, hepatic, or neurologic toxicity, = gr3 rectal or genitourinary bleeding, = gr3 left ventricular failure, or = gr2 other cardiac toxicity. The study was designed to estimate the rate of acute treatment-related toxicity separately in each group of patients. Using the Fleming's one-sample multiple test procedure with Type I and II errors each set at 10%, 40 cases/group were required to reject the null hypothesis that the true toxicity rate is greater than 25% in favor of the alternative hypothesis that the true rate is no more than 10%. Six or more patients with the designated toxicities out of 40 would result in rejecting the null hypothesis.	From start of protocol treatment to 90 days
Secondary	Treatment Completion	The number of patients within each group who completed all elements of protocol treatment are reported.	From registration to end of treatment; up to 64 days."
Secondary	Complete Response to Treatment	The number of patients within each group who achieved a complete response to protocol treatment by 12 weeks are reported. Complete response is defined as no gross tumor at cystoscopy or negative biopsies or both by week 12 after completion of protocol treatment.	At 12 weeks from treatment start
Secondary	Progression-free Survival	Disease (failure) is defined as any bladder cancer progression determined by all measures of disease including physical exam, imaging, and biopsies. Disease-free survival time is defined as time from treatment start to the date of first progression, death, or last known follow-up (censored). Disease-free survival rates are estimated using the Kaplan-Meier method. Analysis occurred after all patients had been on study for at least 5 years. This is a non-randomized phase I/II trial in which the two patient groups are not compared.	From start of treatment to last follow-up. Maximum follow-up at time of analysis was 9.9 years.
Secondary	Overall Survival	Overall survival time is defined as time from treatment start to the date of death from any cause or last known follow-up (censored). Overall survival rates are estimated using the Kaplan-Meier method. Analysis occurred after all patients had been on study for at least 5 years. This is a non-randomized phase I/II trial in which the two patient groups are not compared.	From the date of treatment started to death, assessed up to at least 5 years