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 15, 2016
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
Bladder Urothelial Carcinoma
Stage I Bladder Cancer
Stage II Bladder Cancer
Stage III Bladder Cancer
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: From start of protocol treatment to 90 days ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Treatment Completion [ Time Frame: From registration to end of treatment; up to 64 days." ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.

  • Five-year 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.

  • Five-year 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: 70
Study Start Date: July 2005
Study Completion Date: February 2014
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: HER2+ :RT, Paclitaxel, and Trastuzumab
Paclitaxel and trastuzumab chemotherapy with concurrent with radiation therapy
Drug: Paclitaxel
50 mg/m2 intravenously on days 1, 8, 15, 22, 29, 36, and 43 of radiation therapy
Other Names:
  • Anzatax
  • TAX
Biological: Trastuzumab
Intravenously 4 mg/kg on day 1 of radiation therapy, then 2 mg/kg on days 8, 15, 22, 29, 36, and 43 of radiation therapy.
Other Names:
  • ABP 980
  • PF-05280014
  • rhuMAb HER2
Radiation: Radiation Therapy
Once daily fractions of 1.8 Gy to small pelvic fields 5 days per week for 22 fractions, then once daily fractions of 1.8 Gy to reduced fields 5 days per week for 8 fractions, for a total of 64.8 Gy in 36 fractions.
Other Names:
  • Irradiate
  • Irradiated
  • Irradiation
  • RT
Experimental: HER2- :RT and Paclitaxel
Paclitaxel chemotherapy concurrent with radiation therapy
Drug: Paclitaxel
50 mg/m2 intravenously on days 1, 8, 15, 22, 29, 36, and 43 of radiation therapy
Other Names:
  • Anzatax
  • TAX
Radiation: Radiation Therapy
Once daily fractions of 1.8 Gy to small pelvic fields 5 days per week for 22 fractions, then once daily fractions of 1.8 Gy to reduced fields 5 days per week for 8 fractions, for a total of 64.8 Gy in 36 fractions.
Other Names:
  • Irradiate
  • Irradiated
  • Irradiation
  • RT

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, abbreviated as HER2+ and HER2-, respectively.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
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
  • 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 (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
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: NCT00238420

  Show 155 Study Locations
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: M. Dror Michaelson Radiation Therapy Oncology Group
  More Information

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
Results First Received: December 10, 2015
Last Updated: April 15, 2016
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on July 26, 2016