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

• 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: National Cancer Institute (NCI)
• Collaborator: Radiation Therapy Oncology Group
• Information provided by (Responsible Party): National Cancer Institute (NCI)

Tracking Information

• First Submitted Date: October 12, 2005
• First Posted Date: October 13, 2005
• Results First Submitted Date: December 10, 2015
• Results First Posted Date: May 23, 2016
• Last Update Posted Date: July 19, 2022
• Actual Study Start Date: July 26, 2005
• Actual Primary Completion Date: February 5, 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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: Not Provided

Current Secondary Outcome Measures (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: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Paclitaxel and Radiation Therapy With or Without Trastuzumab in Treating Patients Who Have Undergone Surgery for Bladder Cancer
• 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
• 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: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• 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

• 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

• 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

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 15, 2016): 70
• Original Enrollment: Not Provided
• Actual Study Completion Date: May 20, 2022
• Actual Primary Completion Date: February 5, 2014 (Final data collection date for primary outcome measure)

Eligibility 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 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

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, United States

Administrative Information

• NCT Number: NCT00238420
• Other Study ID Numbers: 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: Not Provided
• Current Responsible Party: National Cancer Institute (NCI)
• Original Responsible Party: Not Provided
• Current Study Sponsor: National Cancer Institute (NCI)
• Original Study Sponsor: Radiation Therapy Oncology Group
• Collaborators: Radiation Therapy Oncology Group

Investigators

• Principal Investigator: M. D Michaelson; Radiation Therapy Oncology Group

• PRS Account: National Cancer Institute (NCI)
• Verification Date: May 2022