Adjuvant Versus Progression-Triggered Gemcitabine Monotherapy for Locally Advanced Bladder Cancer

NCT00146276 | Unknown Phase 3

• 2 other identifiers: B9E-MC-S062AB 22/00
• Study Type: interventional
• Target: 178
• Locations: 1 country
• Sites: 1

Brief Summary

Primary Objective:

• To analyse time to tumor progression in patients cystectomized for locally advanced transitional cell carcinoma (TCC) of the bladder, who are not suitable for cisplatin-based chemotherapy (i.e. postoperative reduced renal function, advanced age). Patients are randomized to receive either adjuvant gemcitabine immediately after radical operation (treatment arm A) or no treatment (control arm B). Patients in the control arm are to be treated with gemcitabine as soon as tumor progression becomes evident clinically and/or radiologically. Secondary Objectives: The secondary objectives of this study are:
• Estimation of time-specific survival probabilities irrespective of causes of death.
• Assessment of toxicity and tolerability of gemcitabine
• Description of survival experience of patients in the control arm beyond the time of initiating chemotherapy.
• Assessment of quality of life (European Organization for Research and Treatment of Cancer \[EORTC\] Quality of Life Questionnaire \[QLQ\]-C30). Study Design: This is an open-label, prospective, multicenter, randomized, controlled phase 3 two-arm study using gemcitabine as a single agent in chemonaive cystectomy patients with locally advanced TCC of the bladder in an adjuvant setting. The patients will receive the following treatment: Arm A (treatment): gemcitabine 1250 mg/m2 intravenously once a week for 2 weeks (days 1 and 8) followed by 1-week rest period. Repeat cycle on day 22. Maximum of 6 cycles. Begin treatment until 3 months after radical operation (within first 6 weeks is recommended). Arm B (control): No immediate post-surgery treatment. Watchful waiting; treatment only conditionally in case of progression with gemcitabine (dose and schedule as in arm A).

Conditions

Bladder Cancer; Carcinoma, Transitional Cell

Keywords

bladder cancer; cystectomy; gemcitabine; adjuvant chemotherapy; locally advanced bladder cancer

Outcome Measures

Primary Outcomes (1)

• progression-free survival

Secondary Outcomes (3)

• overall survival

• toxicity and tolerability of gemcitabine

• quality of life (EORTC QLQ-C30, version 2.0)

Interventions

gemcitabine DRUG

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Status after radical cystectomy for transitional cell carcinoma of the bladder, stages pT3a, pT3b, pT4a and/or pN1, pN2 (but no more than 5 lymph nodes positive for tumor) \[International Union Against Cancer (UICC) criteria, 1997\]. Transitional cell carcinoma may be with or without squamous cell carcinoma and/or adenocarcinoma components. Complete tumor removal by radical operation has to be established macroscopically and microscopically (R0 resection).
• Patients regarded as inappropriate for cisplatin-based chemotherapy (i.e. impaired renal function with at least 30 ml/min calculated creatinine clearance and serum-creatinine less than 3.0 mg/dl, age \> 70) are eligible for study enrollment \[calculation of creatinine clearance according to Cockcroft and Gault formula\]. Decision left to the investigator's discretion.
• Patient has no prior history of systemic chemotherapy regimens. Previous local intravesical adjuvant chemotherapy or immunotherapy is allowed.
• Prior radiation therapy is allowed if it has been completed at least 12 weeks before enrollment into the study and the patient has recovered from all toxic effects.
• Performance status of 60 or higher on the Karnofsky Scale.
• Patient compliance, mental state, and geographic proximity allow adequate followup
• Adequate bone marrow reserve: white blood cell (WBC) count \>= 3.5 x 10\^9/L, platelets \>= 100 x 10\^9/L, and hemoglobin \>= 10 g/dL (or \>= 6.2 mmol/L or \>= 100 g/L).
• Adequate liver function with bilirubin \< 1.25 times above upper limit of normal range; alanine transaminase (ALT) or aspartate transaminase (AST) \< 2.5 times normal upper limit.
• Males or females at least 18 years of age who are considered fit for gemcitabine chemotherapy.
• Signed informed consent by the patient.

You may not qualify if:

• Tumor was not completely removed (visible tumor or enlarged lymph nodes left or positive margins microscopically-R1 or R2 resection)
• Patient has a distant metastasis or metastases.
• Tumor stage pT4b or more than 5 locoregional lymph nodes are positive for tumor.
• Adeno- and/or squamous cell carcinoma of the bladder without transitional cell carcinoma component (different responses to chemotherapy).
• Time interval between radical cystectomy and the first day of chemotherapy exceeds 3 months for patients enrolled in the treatment arm.
• Serum creatinine \>= 3.0 mg/dl (\>= 265 mmol/l)
• Active infection (at the discretion of the investigator) .
• Serious concomitant systemic disorders incompatible with the study (at the discretion of the investigator)
• Patients with a history of prior malignancy other than basal or squamous cell carcinoma of the skin, in situ carcinoma of the cervix or incidental carcinoma of the prostate must be clinically free of disease for at least 5 years prior to study entry.
• Use of any investigational agent in the month before enrollment into the study.
• White blood cell (WBC) count \< 3.5 x 10\^9/L or platelets \< 100 x 10\^9/L or hemoglobin \< 10 g/dL (or \< 6.2 mmol/L or \< 100 g/L).
• Bilirubin \>= 1.25 times above upper limit of normal range; alanine transaminase (ALT) or aspartate transaminase (AST) \>= 2.5 times upper limit of normal range

Sponsors & Collaborators

• Association of Urologic Oncology (AUO): lead
• Eli Lilly and Company: collaborator

Study Sites (1)

Saarland University

Homburg/Saar, Saarland, 66421, Germany

RECRUITING

Related Links

• see "Aktivierte Studien/Blase"

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Carcinoma, Transitional Cell

Interventions

Gemcitabine

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Michael Stöckle, MD

  Dept of Urology, Saarland University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jan Lehmann, MD

CONTACT

+49-(0)6841-1624700; jan.lehmann@uniklinikum-saarland.de

Michael Stöckle, MD

CONTACT

+49-(0)6841-1624700; michael.stoeckle@uniklinikum-saarland.de

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: September 2, 2005
• First Posted: September 7, 2005
• Study Start: July 1, 2000
• Last Updated: September 27, 2006

Record last verified: 2005-09

Locations

DE (1)