S0121, Neoadjuvant Carboplatin, Paclitaxel, and Gemcitabine Followed by Cisplatin and Radiation Therapy in Treating Patients With Locally Advanced or Recurrent Carcinoma of the Urothelium

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Southwest Oncology Group
ClinicalTrials.gov Identifier:
NCT00055835
First received: March 6, 2003
Last updated: January 30, 2013
Last verified: January 2013
  Purpose

RATIONALE: Drugs used in chemotherapy, such as carboplatin, paclitaxel, gemcitabine, and cisplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Giving chemotherapy before radiation therapy, and combining chemotherapy with radiation therapy, may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of neoadjuvant gemcitabine, paclitaxel, and carboplatin followed by cisplatin and radiation therapy in treating patients who have locally advanced or recurrent carcinoma (cancer) of the urothelium.


Condition Intervention Phase
Bladder Cancer
Urethral Cancer
Drug: carboplatin
Drug: cisplatin
Drug: gemcitabine hydrochloride
Drug: paclitaxel
Procedure: neoadjuvant therapy
Radiation: radiation therapy
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Evaluation of Carboplatin, Paclitaxel and Gemcitabine Followed by Concurrent Cisplatin and Radiation Therapy in Patients With Locally Advanced or Recurrent Urothelial Malignancy

Resource links provided by NLM:


Further study details as provided by Southwest Oncology Group:

Enrollment: 7
Study Start Date: November 2002
Study Completion Date: June 2006
Primary Completion Date: June 2006 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: carboplatin
    *AUC=5 (by modified Calvert formula), IV, over 15 minutes; given q 21 days for a maximum of 3 cycles (1 cycle = 21 days)
    Other Name: Paraplatin
    Drug: cisplatin
    75 mg/m2 (maximum dose 150 mg), IV, rapid infusion; given q 21 days for 2 cycles (1 cycle = 21 days)
    Other Name: Platinol; CDDP
    Drug: gemcitabine hydrochloride
    800 mg/m2, IV, over 30 minutes; given on Days 1 & 8, q 21 days, for a maximum of 3 cycles (1 cycle = 21 days)
    Other Name: Gemzar
    Drug: paclitaxel
    200 mg/m2, IV, over 3 hours; given q 21 days for a maximum of 3 cycles (1 cycle = 21 days)
    Other Name: Taxol
    Procedure: neoadjuvant therapy
    Neoadjuvant chemotherapy (paclitaxel, carboplatin, and gemcitabine)
    Radiation: radiation therapy
    Radiation treatments will be delivered once daily. Treatment will be given 5 days per week at a dose of 180 to 200 cGy per day. All fields will be treated everyday.
Detailed Description:

OBJECTIVES:

  • Determine the overall survival of patients with locally advanced or recurrent carcinoma of the urothelium treated with neoadjuvant carboplatin, paclitaxel, and gemcitabine followed by concurrent cisplatin and radiotherapy.
  • Determine the feasibility of administering this regimen to these patients.
  • Determine the progression-free survival of patients treated with this regimen.
  • Determine the qualitative and quantitative toxic effects of this regimen in these patients.
  • Determine the response rate (confirmed and unconfirmed) of patients treated with the neoadjuvant regimen and those treated with the whole regimen.
  • Determine the proportion of patients who qualify for concurrent cisplatin and radiotherapy after receiving the neoadjuvant regimen.
  • Determine the potential value of suppressor gene expression analysis (p53 and retinoblastoma gene) and HER2 expression as indicators of prognosis and/or response in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive neoadjuvant chemotherapy comprising paclitaxel IV over 3 hours and carboplatin IV over 15 minutes on day 1 and gemcitabine IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for a maximum of 3 courses in the absence of disease progression or unacceptable toxicity.

Within 4-8 weeks after the completion of neoadjuvant chemotherapy, patients receive cisplatin IV over 30-60 minutes on day 1. Treatment repeats every 21 days for a maximum of 2 courses in the absence of disease progression or unacceptable toxicity. Patients also undergo concurrent radiotherapy 5 days a week for 6 weeks.

Patients are followed every 3 months for 2 years and then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 80 patients will be accrued for this study within 4 years.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Histologically confirmed primary or recurrent invasive carcinoma of the urothelium

    • Transitional, squamous, or mixed cell subtypes allowed
    • Primary disease site must be the urinary bladder or urethra
    • Disease confined to the true pelvis (T2-T4, N0-N3, M0)
    • Must meet at least 1 of the following criteria:

      • Nodal involvement at or below the level of the bifurcation of the iliac vessels
      • Medically or surgically inoperable
      • Patient refused cystectomy
  • Measurable or nonmeasurable disease
  • Evidence of tumor invasion of the muscularis by cystoscopy and biopsy and detailed bladder mapping within the past 56 days
  • No extrapelvic metastases
  • Eligible to receive radiotherapy

    • Planned radiotherapy at a SWOG-approved facility

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • Zubrod 0-2

Life expectancy

  • Not specified

Hematopoietic

  • Granulocyte count at least 1,500/mm^3
  • Platelet count at least lower limit of normal

Hepatic

  • Bilirubin no greater than upper limit of normal (ULN)
  • SGOT or SGPT no greater than 2.5 times ULN

Renal

  • Creatinine clearance at least 60 mL/min OR
  • Creatinine no greater than ULN

Gastrointestinal

  • No chronic diarrhea
  • No malabsorption
  • No extensive diverticular disease of the colon
  • No inflammatory bowel disease
  • No other pre-existing gastrointestinal disorders

Other

  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • No active infections requiring antibiotics
  • No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer currently in complete remission

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Not specified

Chemotherapy

  • No prior chemotherapy for patients with a current diagnosis of advanced bladder cancer that is also the initial diagnosis
  • No prior systemic chemotherapy except adjuvant therapy for recurrent disease completed more than 6 months ago
  • No prior carboplatin
  • No prior paclitaxel
  • No prior gemcitabine

Endocrine therapy

  • Not specified

Radiotherapy

  • See Disease Characteristics
  • No prior pelvic radiotherapy

Surgery

  • See Disease Characteristics
  • Recovered from prior surgery
  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: NCT00055835

  Show 92 Study Locations
Sponsors and Collaborators
Southwest Oncology Group
Investigators
Study Chair: Ulka N. Vaishampayan, MD Barbara Ann Karmanos Cancer Institute
  More Information

Additional Information:
No publications provided

Responsible Party: Southwest Oncology Group
ClinicalTrials.gov Identifier: NCT00055835     History of Changes
Other Study ID Numbers: CDR0000271309, S0121, U10CA032102
Study First Received: March 6, 2003
Last Updated: January 30, 2013
Health Authority: United States: Federal Government

Keywords provided by Southwest Oncology Group:
recurrent bladder cancer
stage III bladder cancer
squamous cell carcinoma of the bladder
stage II bladder cancer
recurrent urethral cancer
urethral cancer associated with invasive bladder cancer
distal urethral cancer
proximal urethral cancer
stage IV bladder cancer
transitional cell carcinoma of the bladder

Additional relevant MeSH terms:
Urinary Bladder Neoplasms
Urethral Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Urinary Bladder Diseases
Urologic Diseases
Urethral Diseases
Gemcitabine
Cisplatin
Carboplatin
Paclitaxel
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on July 28, 2014