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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00238420
Recruitment Status : Completed
First Posted : October 13, 2005
Results First Posted : May 23, 2016
Last Update Posted : July 19, 2022
Sponsor:
Collaborator:
Radiation Therapy Oncology Group
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Tracking Information
First Submitted Date  ICMJE October 12, 2005
First Posted Date  ICMJE October 13, 2005
Results First Submitted Date  ICMJE December 10, 2015
Results First Posted Date  ICMJE May 23, 2016
Last Update Posted Date July 19, 2022
Actual Study Start Date  ICMJE July 26, 2005
Actual Primary Completion Date February 5, 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 15, 2016)
Acute Treatment-related Toxicity [ Time Frame: From start of protocol treatment to 90 days ]
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.
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 4, 2021)
  • Treatment Completion [ Time Frame: From registration to end of treatment; up to 64 days." ]
    The number of patients within each group who completed all elements of protocol treatment are reported.
  • Complete Response to Treatment [ Time Frame: At 12 weeks from treatment start ]
    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.
  • Progression-free Survival [ Time Frame: From start of treatment to last follow-up. Maximum follow-up at time of analysis was 9.9 years. ]
    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.
  • Overall Survival [ Time Frame: From the date of treatment started to death, assessed up to at least 5 years ]
    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.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Paclitaxel and Radiation Therapy With or Without Trastuzumab in Treating Patients Who Have Undergone Surgery for Bladder Cancer
Official Title  ICMJE 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
Brief 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.
Detailed 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • 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
Intervention  ICMJE
  • Drug: Paclitaxel
    Given IV
    Other Names:
    • Anzatax
    • Asotax
    • Bristaxol
    • Praxel
    • Taxol
    • Taxol Konzentrat
  • Radiation: Radiation Therapy
    Undergo radiation therapy
    Other Names:
    • Cancer Radiotherapy
    • ENERGY_TYPE
    • Irradiate
    • Irradiated
    • Irradiation
    • Radiation
    • Radiation Therapy, NOS
    • Radiotherapeutics
    • Radiotherapy
    • RT
    • Therapy, Radiation
  • Biological: Trastuzumab
    Given IV
    Other Names:
    • ABP 980
    • ALT02
    • Anti-c-ERB-2
    • Anti-c-erbB2 Monoclonal Antibody
    • Anti-ERB-2
    • Anti-erbB-2
    • Anti-erbB2 Monoclonal Antibody
    • Anti-HER2/c-erbB2 Monoclonal Antibody
    • Anti-p185-HER2
    • c-erb-2 Monoclonal Antibody
    • HER2 Monoclonal Antibody
    • Herceptin
    • Herceptin Biosimilar PF-05280014
    • Herceptin Trastuzumab Biosimilar PF-05280014
    • Herzuma
    • Kanjinti
    • MoAb HER2
    • Monoclonal Antibody c-erb-2
    • Monoclonal Antibody HER2
    • Ogivri
    • Ontruzant
    • PF-05280014
    • rhuMAb HER2
    • RO0452317
    • SB3
    • Trastuzumab Biosimilar ABP 980
    • Trastuzumab Biosimilar ALT02
    • trastuzumab biosimilar EG12014
    • Trastuzumab Biosimilar HLX02
    • Trastuzumab Biosimilar PF-05280014
    • Trastuzumab Biosimilar SB3
    • Trastuzumab Biosimilar SIBP-01
    • Trastuzumab-anns
    • Trastuzumab-dkst
    • Trastuzumab-dttb
    • Trastuzumab-pkrb
    • Trastuzumab-qyyp
    • Trazimera
Study Arms  ICMJE
  • 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.
    Interventions:
    • Drug: Paclitaxel
    • Radiation: Radiation Therapy
    • Biological: Trastuzumab
  • 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.
    Interventions:
    • Drug: Paclitaxel
    • Radiation: Radiation Therapy
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 15, 2016)
70
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE May 20, 2022
Actual Primary Completion Date February 5, 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00238420
Other Study ID Numbers  ICMJE NCI-2009-00730
NCI-2009-00730 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
RTOG-0524
CDR0000440988
RTOG 0524 ( Other Identifier: Radiation Therapy Oncology Group )
RTOG-0524 ( Other Identifier: CTEP )
U10CA180868 ( U.S. NIH Grant/Contract )
U10CA021661 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party National Cancer Institute (NCI)
Original Responsible Party Not Provided
Current Study Sponsor  ICMJE National Cancer Institute (NCI)
Original Study Sponsor  ICMJE Radiation Therapy Oncology Group
Collaborators  ICMJE Radiation Therapy Oncology Group
Investigators  ICMJE
Principal Investigator: M. D Michaelson Radiation Therapy Oncology Group
PRS Account National Cancer Institute (NCI)
Verification Date May 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP