Neoadjuvant Chemotherapy Plus Nephroureterectomy for Locally Advanced Upper Tract Transitional Cell Cancer - Full Text View

Sponsored by:	Lahey Clinic
Information provided by:	Lahey Clinic
ClinicalTrials.gov Identifier:	NCT00696007

Purpose

The purpose of this study is to test the effectiveness, safety and side effects of two chemotherapy drugs (gemcitabine and cisplatin) when combined with surgery after chemotherapy for patients with upper urinary tract cancer. The hypothesis is that undergoing chemotherapy prior to surgery will have a beneficial effect on prognosis and may improve overall survival as in patients with bladder cancer, and will allow better tolerance of chemotherapy than if it were given after surgery.

Condition	Intervention	Phase
Transitional Cell Carcinoma	Drug: Gemcitabine and cisplatin Other: Retrospective comparison	Phase II

MedlinePlus related topics: Cancer

Drug Information available for: Cisplatin Gemcitabine hydrochloride Gemcitabine

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Parallel Assignment, Safety/Efficacy Study
Official Title:	Neoadjuvant Chemotherapy Plus Nephroureterectomy for Locally Advanced Upper Tract Transitional Cell Cancer

Further study details as provided by Lahey Clinic:

Primary Outcome Measures:

Neoadjuvant chemotherapy (Gemcitabine and Cisplatin) Regime (3 cycles) before Nephroureterectomy [ Time Frame: 5 years: follow ups 1st year/every 4 mths, 2nd & 3rd year to every 6 months, 4th & 5th yr-annually for patients who remain disease free ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Overall survival compared to institutional historical cohort of subjects who have undergone a nephroureterectomy alone. [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	120
Study Start Date:	April 2008
Estimated Study Completion Date:	April 2019
Estimated Primary Completion Date:	April 2018 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental A neoadjuvant chemotherapy (gemcitabine and cisplatin) regimen administered before surgery-nephroureterectomy for upper tract TCC	Drug: Gemcitabine and cisplatin Neoadjuvant chemotherapy (gemcitabine and cisplatin) administered before Nephroureterectomy. Chemotherapy regimen of three cycles of gemcitabine and cisplatin, dosed over a 3 month period Each cycle would consist of gemcitabine and cisplatin on day 1, with two other doses of gemcitabine on day 8 and day 15. Gemcitabine dosing would be 1,000 mg/m² and cisplatin would be dosed at 70 mg/m²
2 A retrospective cohort group (approximately 60 subjects) identified from an institutional cancer registry who have undergone a nephroureterectomy alone over the past five years	Other: Retrospective comparison 60 retrospective historical cohort group of subjects who have undergone a radical nephroureterectomy over the past five years

Arms

Assigned Interventions

1: Experimental

A neoadjuvant chemotherapy (gemcitabine and cisplatin) regimen administered before surgery-nephroureterectomy for upper tract TCC

Drug: Gemcitabine and cisplatin

Neoadjuvant chemotherapy (gemcitabine and cisplatin) administered before Nephroureterectomy.

Chemotherapy regimen of three cycles of gemcitabine and cisplatin, dosed over a 3 month period Each cycle would consist of gemcitabine and cisplatin on day 1, with two other doses of gemcitabine on day 8 and day 15.

Gemcitabine dosing would be 1,000 mg/m² and cisplatin would be dosed at 70 mg/m²

2

A retrospective cohort group (approximately 60 subjects) identified from an institutional cancer registry who have undergone a nephroureterectomy alone over the past five years

Other: Retrospective comparison

60 retrospective historical cohort group of subjects who have undergone a radical nephroureterectomy over the past five years

Detailed Description:

This study will look at improving overall survival of those undergoing nephroureterectomy for upper tract TCC (transitional cell carcinoma, comparing the pathological response of tumors treated with Neoadjuvant Chemotherapy (gemcitabine and cisplatin) before surgery. There have been reported studies of neoadjuvant chemotherapy in the treatment of upper tract TCC, there have been no studies to date that include the chemotherapy agents gemcitabine and cisplatin that are currently indicated in treating TCC of the bladder in the neoadjuvant and adjuvant setting. These agents have been proven to have a better overall safety profile and tolerability allowing more patients to complete their regimens. Secondarily, study will compare disease free overall survival among patients treated with neoadjuvant chemotherapy and surgery versus surgery alone. This study may elucidate the potential benefit of these agents when treating TCC of the upper tracts and may provide a survival advantage in this specific patient population as compared to a historical cohort.

Eligibility

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

Criteria

Inclusion Criteria:

ECOG performance status 0-2
Estimated GFR>60
High grade TCC on initial biopsy
Clinical stage T1-T3, Nx, Mx based on the AJCC Classification system
TCC confined to the ureter or renal pelvis
Grade II neuropathy or less

Exclusion Criteria:

Any other malignancy over the previous five years with a risk of relapse that exceeds 30%
History of previous cystectomy
Evidence of metastatic disease
History of pelvic irradiation or prior chemotherapy

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00696007

Contacts

Contact: Christopher G. Tretter, M.D.	781-744-8410	Christopher.G.Tretter@Lahey.org
Contact: Krista V. Marcello	781-744-3071	Krista.V.Marcello@Lahey.org

Locations

United States, Massachusetts
Lahey Clinic, Inc.	Recruiting
Burlington, Massachusetts, United States, 01805
Contact: Christopher G. Tretter, M.D. 781-744-8410 Christopher.G.Tretter@Lahey.org
Contact: Krista V. Marcello 781-744-3071 Krista.V.Marcello@Lahey.org
Sub-Investigator: Alireza Moinzadeh, M.D.
Sub-Investigator: Justin Gould, M.D.
Sub-Investigator: Andrea Sorcini, M.D.
Sub-Investigator: John Libertino, M.D.
Sub-Investigator: Ingolf Tuerk, M.D.
Sub-Investigator: Timothy Cooley, M.D.

Sponsors and Collaborators

Lahey Clinic

Investigators

Principal Investigator:

Christopher G. Tretter, M.D.

Lahey Clinic, Inc.

More Information

Publications:

Splinter TA, Pavone-Macaluso M, Jacqmin D, Roberts JT, Carpentier P, de Pauw M, Sylvester R. A European Organization for Research and Treatment of Cancer--Genitourinary Group phase 2 study of chemotherapy in stage T3-4N0-XM0 transitional cell cancer of the bladder: evaluation of clinical response. J Urol. 1992 Dec;148(6):1793-6.

Raman JD, Sosa RE, Vaughan ED Jr, Scherr DS. Pathologic features of bladder tumors after nephroureterectomy or segmental ureterectomy for upper urinary tract transitional cell carcinoma. Urology. 2007 Feb;69(2):251-4.

Brown GA, Busby JE, Wood CG, Pisters LL, Dinney CP, Swanson DA, Grossman HB, Pettaway CA, Munsell MF, Kamat AM, Matin SF. Nephroureterectomy for treating upper urinary tract transitional cell carcinoma: Time to change the treatment paradigm? BJU Int. 2006 Dec;98(6):1176-80.

Keeley FX, Kulp DA, Bibbo M, McCue PA, Bagley DH. Diagnostic accuracy of ureteroscopic biopsy in upper tract transitional cell carcinoma. J Urol. 1997 Jan;157(1):33-7.

Hall MC, Womack S, Sagalowsky AI, Carmody T, Erickstad MD, Roehrborn CG. Prognostic factors, recurrence, and survival in transitional cell carcinoma of the upper urinary tract: a 30-year experience in 252 patients. Urology. 1998 Oct;52(4):594-601.

Grossman HB, Natale RB, Tangen CM, Speights VO, Vogelzang NJ, Trump DL, deVere White RW, Sarosdy MF, Wood DP Jr, Raghavan D, Crawford ED. Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. N Engl J Med. 2003 Aug 28;349(9):859-66. Erratum in: N Engl J Med. 2003 Nov 6;349(19):1880.

Igawa M, Urakami S, Shiina H, Kishi H, Himeno Y, Ishibe T, Kadena H, Usui T. Neoadjuvant chemotherapy for locally advanced urothelial cancer of the upper urinary tract. Urol Int. 1995;55(2):74-7.

Responsible Party:	Lahey Clinic, Inc. ( Christopher G. Tretter, M.D. )
Study ID Numbers:	2008-039
Study First Received:	June 10, 2008
Last Updated:	July 21, 2008
ClinicalTrials.gov Identifier:	NCT00696007
Health Authority:	United States: Institutional Review Board

Keywords provided by Lahey Clinic:

Upper GU Tract Transitional Cell Carinoma
Nephroureterectomy
Chemotherapy
Gemcitabine
Cisplatin

Study placed in the following topic categories:

Cisplatin
Gemcitabine
Carcinoma, Transitional Cell

Transitional cell carcinoma
Neoplasms, Glandular and Epithelial
Carcinoma

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Neoplasms by Histologic Type
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs

Enzyme Inhibitors
Immunosuppressive Agents
Antiviral Agents
Pharmacologic Actions
Neoplasms
Radiation-Sensitizing Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on January 15, 2009