Fluorouracil, Leucovorin, Gemcitabine, and Cisplatin in Treating Patients With Metastatic or Unresectable Adenocarcinoma of the Urothelium or Urachal Remnant

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00082706
First received: May 14, 2004
Last updated: December 18, 2013
Last verified: December 2013
  Purpose

RATIONALE: Drugs used in chemotherapy, such as fluorouracil, leucovorin, gemcitabine, and cisplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving fluorouracil together with leucovorin, gemcitabine, and cisplatin works in treating patients with metastatic or unresectable adenocarcinoma of the urothelium or urachal remnant (part of the bladder).


Condition Intervention Phase
Bladder Cancer
Urethral Cancer
Urachal Cancer
Drug: 5-Fluorouracil (5-FU)
Drug: Leucovorin
Drug: Cisplatin
Drug: Gemcitabine
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of 5-FU, Leucovorin, Gemcitabine, and Cisplatin for Adenocarcinomas of the Urothelial Tract and Urachal Remnant

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Number of Patients with Response [ Time Frame: Every 2 cycles (6 weeks) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number of Patients with Dose-Limiting Toxicity [ Time Frame: Continous assessment during 21 day cycles ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 46
Study Start Date: April 2003
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 5-FU, Leucovorin, Gemcitabine + Cisplatin
5-FU continuous infusion over Days 1 - 5; Leucovorin once a day as a short infusion on Days 1 - 5; Cisplatin infusion over a few hours (usually 2-4 hours) once a day on Days 1 - 5; Gemcitabine infusion over 30 minutes on Days 1 & 5 only.
Drug: 5-Fluorouracil (5-FU)
Day: 1 - 5 Dose: 200 mg/m2 IVCI daily x 5 days
Other Names:
  • 5-FU
  • Adrucil
  • Efudex
Drug: Leucovorin
Day: 1 - 5 Dose:10 mg/m2 daily x 5 days
Other Names:
  • Citrvorum
  • Wellcovorin
Drug: Cisplatin
Day: 1 - 5 Dose: 20 mg/m2 daily x 5 days
Other Names:
  • Platinol-AQ
  • Platinol
  • CDDP
Drug: Gemcitabine
Day: 1 & 5 Dose: 200 mg/m2 (Two doses only)
Other Names:
  • Gemcitabine Hydrochloride
  • Gemzar

Detailed Description:

OBJECTIVES:

Primary

  • Determine the response rate and overall survival of patients with metastatic or unresectable adenocarcinoma of the urothelium or urachal remnant treated with fluorouracil, leucovorin calcium, gemcitabine, and cisplatin.

Secondary

  • Determine the toxicity of this regimen in these patients.

OUTLINE: Patients are stratified according to diagnosis (adenocarcinoma of the urothelium vs adenocarcinoma of the urachal remnant).

Patients receive fluorouracil by vein (IV) continuously, leucovorin calcium IV once daily, and cisplatin IV once daily on days 1-5 and gemcitabine IV on days 1 and 5. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3-6 months.

PROJECTED ACCRUAL: A total of 23-46 patients (7-18 with adenocarcinoma of the urachal remnant and 16-28 with adenocarcinoma of the urothelium) will be accrued for this study.

  Eligibility

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

Inclusion Criteria:

  1. Histologic proof of cancer originating from the urinary tract with adenocarcinoma as the predominant (>/= 50%) histology. Dr. Czerniak and/or Dr. Tamboli will be consulted in equivocal cases of mixed histology. The Study Chairman is the final arbiter in questions of mixed histology.
  2. Bi-dimensionally measurable disease. All patients must have measurable or evaluable disease. In general, liver and lung lesions should be at least 1 cm, and patients with node-only disease should have lesions of >/= 1.5 cm in greatest dimension. Patients with disease confined to bone may be eligible if a measurable lytic defect, or soft-tissue component in present. Those without measurable disease may be eligible if a serum marker is elevated (>/= 4 x ULN) (ie: CEA, CA-125, CA19-9, bhCG, etc).
  3. (# 2 cont'd) The Study Chairman is the final arbiter in questions related to measurability. Patients with a three-dimensional mass or pelvic sidewall fixation on bladder examination under anesthesia are considered to have measurable disease.
  4. Patients are eligible if they have evidence of metastatic disease, or if their tumor is surgically unresectable. In the absence of grossly metastatic disease, all patients should be seen and evaluated by a member of the Urology staff to assess their potential for resection.
  5. Patients must have adequate physiologic reserves as evidenced by: • Life expectancy of at least 9 months (based on co-morbidity) & at least 9 weeks based on the natural history of their cancer. • Zubrod Performance Status (PS) of </= 2; or 3 if of recent onset and due entirely to the cancer and not to comorbidity, and especially if the compromised performance status is due to uncontrolled pain which is expected to be rapidly reversible when therapy starts.
  6. (#5 cont'd) • Adequate bone marrow function as defined by absolute neutrophil count >/= 1,800 and platelet count >/= 150,000. Supranormal values judged to be of benign or inconsequential etiology are acceptable. • Transaminase (either SGPT or SGOT) </= 2x the upper limit of normal. • Conjugated bilirubin </= 2x the upper limit of normal. • Creatinine clearance (either measured or estimated using the formula of Cockcroft and Gault) of >/= 35 mL/min: CLcr = [(140-age) • wt(kg)]/[72 •Creat (mg/dL)] (For females, x 0.85)
  7. Patients must sign an informed consent indicating that they are aware of the investigational nature of this study, in keeping with the policies of this hospital.
  8. Patients must be at least 6 weeks out from pelvic irradiation, and must not have had more than 10% of the bone marrow irradiated.
  9. Patients with a history of cardiac disease, or evidence of ischemic heart disease on EKG must have adequate cardiac function with an EF >/= 40% to participate.
  10. Patient must be at least 18 years of age to participate in this study.

Exclusion Criteria:

  1. Patients with metastases to the bladder from a primary adenocarcinoma arising outside the urinary tract are ineligible.
  2. Overt psychosis or mental disability or otherwise incompetent to give informed consent.
  3. A life threatening illness (unrelated to tumor) that would prevent completion of protocol therapy.
  4. Pregnant or nursing women, as the drug therapy regimen, and support medications pose significant potential risks to the fetus and newborn.
  5. Patients with second malignancies are eligible provided that the expected outcome from the second cancer is such that this will not interfere in the delivery of this therapy, or the assessment of response.
  6. Patients with uncontrolled CNS metastases are not eligible.
  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: NCT00082706

Locations
United States, Texas
M. D. Anderson Cancer Center at University of Texas
Houston, Texas, United States, 77030-4009
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Principal Investigator: Arlene Siefker-Radtke, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00082706     History of Changes
Other Study ID Numbers: ID03-0111, P50CA091846, P30CA016672, MDA-ID-030111, CDR0000355828
Study First Received: May 14, 2004
Last Updated: December 18, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
adenocarcinoma of the bladder
recurrent bladder cancer
stage IV bladder cancer
recurrent urethral cancer
anterior urethral cancer
posterior urethral cancer
urethral cancer associated with invasive bladder cancer
stage III bladder cancer

Additional relevant MeSH terms:
Adenocarcinoma
Urinary Bladder Neoplasms
Urethral Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Urinary Bladder Diseases
Urologic Diseases
Urethral Diseases
Gemcitabine
Cisplatin
Fluorouracil
Leucovorin
Levoleucovorin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Vitamin B Complex
Vitamins

ClinicalTrials.gov processed this record on August 27, 2014