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

SWOG Cancer Research Network

Status and phase

Completed

Phase 2

Conditions

Bladder Cancer

Urethral Cancer

Treatments

Drug: cisplatin

Drug: paclitaxel

Drug: gemcitabine hydrochloride

Drug: carboplatin

Radiation: radiation therapy

Procedure: neoadjuvant therapy

Study type

Interventional

Funder types

NETWORK

NIH

Identifiers

NCT00055835

CDR0000271309

S0121 (Other Identifier)

U10CA032102 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment

7 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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