Clinical trial NCT00006351: SCH 66336 Plus Gemcitabine in Treating Patients With Advanced Cancer of the Urinary Tract
Official title: Phase II Study on SCH 66336 (Farnesyl Protein Transferase Inhibitor) and Gemcitabine as Second Line Treatment in Advanced Metastatic Urothelial Cancer - EORTC Study 16997
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Bladder Cancer
Transitional Cell Cancer of the Renal Pelvis and Ureter
Urethral Cancer
Keywords: recurrent bladder cancer
stage IV bladder cancer
transitional cell carcinoma of the bladder
recurrent urethral cancer
anterior urethral cancer
posterior urethral cancer
urethral cancer associated with invasive bladder cancer
metastatic transitional cell cancer of the renal pelvis and ureter
recurrent transitional cell cancer of the renal pelvis and ureter
Lead sponsor: European Organisation for Research and Treatment of Cancer - EORTC
Sponsor class: NETWORK
First posted: 2003-01-27
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining SCH 66336 and gemcitabine may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of SCH 66336 plus gemcitabine in treating patients who have advanced cancer of the urinary tract.

Detailed description: OBJECTIVES:

* Determine the feasibility and toxicity of SCH 66336 and gemcitabine in patients with advanced transitional cell carcinoma of the urinary tract.
* Determine the time to progression and objective response rate of this treatment regimen in these patients.
* Assess the pharmacokinetics of this regimen in these patients.

OUTLINE: This is a multicenter study.

Patients receive gemcitabine IV over 30 minutes on days 1, 8, and 15 and oral SCH 66336 twice a day (starting on day 2 of the first course, and starting on day 1 of all subsequent courses). Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Patients are followed every 8 weeks until disease progression.

PROJECTED ACCRUAL: A total of 7-31 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed metastatic or unresectable primary transitional cell carcinoma of the urinary tract, including bladder, ureter, and renal pelvis
* At least one measurable lesion

  * 20 mm or greater by conventional techniques OR
  * 10 mm or greater by spiral CT scan
* Must have received one (and only one) prior chemotherapy regimen for advanced or metastatic disease
* No clinical signs of brain metastases

PATIENT CHARACTERISTICS:

Age:

* 18 and over

Performance status:

* ECOG 0-2

Life expectancy:

* At least 3 months

Hematopoietic:

* Absolute neutrophil count at least 2,000/mm3
* Platelet count at least 100,000/mm3

Hepatic:

* Bilirubin less than 1.5 times upper limit of normal (ULN)
* Alkaline phosphatase and transaminases no greater than 2.5 times ULN (no greater than 5 times ULN with liver metastases)

Renal:

* Creatinine no greater than 1.7 mg/dL

Cardiovascular:

* Normal cardiac function
* No ischemic heart disease within the past 6 months
* Normal 12 lead ECG

Other:

* No prior gastrectomy or any gastrointestinal disease that may impair absorption of SCH 66336
* No unstable systemic disease
* No active uncontrolled infection
* No psychological, familial, sociological, or geographical condition that would preclude study
* No prior or concurrent other malignancy except cone biopsied carcinoma in situ of the cervix or adequately treated basal or squamous cell skin cancer
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* Not specified

Chemotherapy:

* See Disease Characteristics
* At least 4 weeks since prior chemotherapy
* No prior farnesyl protein transferase inhibitors or gemcitabine

Endocrine therapy:

* Not specified

Radiotherapy:

* At least 4 weeks since prior radiotherapy

Surgery:

* At least 2 weeks since prior major surgery

Other:

* No other concurrent anticancer agents
* No other concurrent investigational therapy

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: University Medical Center Nijmegen
Study officials:
affiliation: Daniel Den Hoed Cancer Center at Erasmus Medical Center
name: Ronald De Wit, MD, PhD
role: STUDY_CHAIR
affiliation: Universitair Medisch Centrum St. Radboud - Nijmegen
name: Pieter H. M. de Mulder, MD, PhD
role: STUDY_CHAIR
affiliation: Free University Medical Center
name: Godefridus Peters, PhD
role: STUDY_CHAIR
References:
citation: Theodore C, Geoffrois L, Vermorken JB, Caponigro F, Fiedler W, Chollet P, Ravaud A, Peters GJ, de Balincourt C, Lacombe D, Fumoleau P. Multicentre EORTC study 16997: feasibility and phase II trial of farnesyl transferase inhibitor & gemcitabine combination in salvage treatment of advanced urothelial tract cancers. Eur J Cancer. 2005 May;41(8):1150-7. doi: 10.1016/j.ejca.2005.02.015.