Gemcitabine and Cisplatin as Neoadjuvant Chemotherapy in Patients With High-Grade Upper Tract Urothelial Carcinoma

NCT01261728 | Completed Phase 2

• 1 other identifier: 10-208
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 9

Brief Summary

The purpose of this study is to see if getting chemotherapy with Gemcitabine and Cisplatin for four 21 day cycles for a total of 12 weeks can help shrink the tumor before undergoing surgery for kidney cancer.

Conditions

Urothelial Carcinoma

Keywords

Gemcitabine; Cisplatin; Bladder; radical nephroureterectomy; ureterectomy; 10-208

Outcome Measures

Primary Outcomes (1)

• To define the pathologic response rate (<pT2)

  of neoadjuvant Gemcitabine and Cisplatin regimen in patients with upper tract high-grade urothelial carcinoma. And is defined as the absence of high-grade carcinoma (\<pT2 disease) and the absence of microscopic lymph node metastases (N0) on the final nephroureterectomy specimen.

  The time to disease progression is measured from the time of initiation of chemotherapyuntil the first date that systemic recurrence is objectively documented.

Secondary Outcomes (3)

• To determine the time to disease progression

  Time to progression is measured from the time of initiation of chemotherapy until the 1st date that systemic recurrence is objectively documented. Systemic recurrence for this trial is defined as either metastatic or local pelvic recurrence.

• To determine overall survival of patients

  3 years

• To evaluate the safety and tolerability

  every 2 weeks per cycle

Study Arms (1)

Gemcitabine and Cisplatin

EXPERIMENTAL

This is a Phase II Study of Gemcitabine and Cisplatin (GC) as neoadjuvant chemotherapy in patients with upper tract high-grade urothelial carcinoma who are candidates for radical nephroureterectomy or distal ureterectomy.

Drug: Gemcitabine and Cisplatin

Interventions

Gemcitabine and Cisplatin DRUG

Patients will receive four cycles of GC administered every 21 days. Gemcitabine 1,000 mg/m2 and Cisplatin 35 mg/m2 will be administered intravenously on days 1 and 8. A total of four cycles of therapy will be administered at 21 day intervals followed by radical nephroureterectomy or distal ureterectomy.

Gemcitabine and Cisplatin

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed high-grade upper tract transitional cell carcinoma at MSKCC or a participating site and/or radiographically visible tumor stage T2-T4a N0/X M0 disease with positive selective urinary cytology or high-grade concomitant bladder tumor. Hydronephrosis associated with tumor on biopsy will be considered invasive by definition.
• Medically appropriate candidate for radical nephroureterectomy or ureterectomy as per MSKCC or a participating site attending urologic oncologist
• Karnofsky Performance Status ≥ 70%
• Age ≥ 18 years of age
• Required Initial Laboratory Values:
• Absolute neutrophil count ≥ 1500 cells/mm3
• Platelets ≥ 100,000 cells/mm3
• Hemoglobin ≥ 9.0g/dL
• Bilirubin ≤ 1.2
• Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x ULN for the institution
• Alkaline phosphatase ≤ 2.5 x ULN for the institution
• Serum creatinine ≤ 1.3 mg/dL if male or ≤ 1.1 mg/dL if female OR calculated creatinine clearance ≥ 55 ml/min/1.73m\^2 If female of childbearing potential, serum pregnancy test is negative.
• Patients with reproductive potential must use an effective method to avoid pregnancy for the duration of the trial.
• ml/min/1.73m2 using the formula: CKD epi : GFR = 141 X min(Scr/κ,1)α X max(Scr/κ,1)-1.209 X 0.993Age X 1.018 \[if female\] X 1.159 \[if black\]
• Scr is serum creatinine, k is 0.7 for females and 0.9 for males, a is -0.329 for females and -0.411 for males, min indicates the minimum of Scr/k or 1, and max indicates the maximum of Scr/k or 1.

You may not qualify if:

• Concomitant bladder urothelial carcinoma is acceptable if it is organ confined and surgically resectable.
• Presence of carcinoma in situ (CIS)
• Prior systemic chemotherapy (prior intravesical therapy is allowed)
• Prior radiation therapy to the bladder
• Evidence of NYHA functional class III or IV heart disease.
• Serious intercurrent medical or psychiatric illness, including serious active infection.
• Preexisting sensory grade 3 neuropathy
• Major surgery or radiation therapy \< 4 weeks of starting study treatment.
• Concomitant use of any other investigational drugs
• Any of the following within the 6 months prior to study drug administration:
• myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, or pulmonary embolism.
• Ongoing cardiac dysrhythmias of NCI CTCAE Version 4.0 grade ≥ 2.
• Uncontrolled hypertension (\>150/100 mmHg despite optimal medical therapy).
• Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness or other active infection. Patients with HIV but no evidence of AIDS will be considered candidates.
• Concurrent treatment on another clinical trial involving an intervention which may affect the primary endpoint. Supportive care trials or non-treatment trials, e.g. QOL, are allowed.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Mayo Clinic: collaborator
• Hartford Hospital: collaborator

Study Sites (9)

Mayo Clinic - Arizona

Scottsdale, Arizona, 85259, United States

Location

Hartford Hospital (Data Collection Only)

Hartford, Connecticut, United States

Location

Memorial Sloan Kettering at Basking Ridge

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Bergen

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Cancer Center @ Suffolk

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau (Consent and Follow-Up only)

Uniondale, New York, 11553, United States

Location

Lehigh Valley Health Network (Data Collection Only)

Allentown, Pennsylvania, 18103, United States

Location

Related Publications (2)

• Coleman JA, Yip W, Wong NC, Sjoberg DD, Bochner BH, Dalbagni G, Donat SM, Herr HW, Cha EK, Donahue TF, Pietzak EJ, Hakimi AA, Kim K, Al-Ahmadie HA, Vargas HA, Alvim RG, Ghafoor S, Benfante NE, Meraney AM, Shichman SJ, Kamradt JM, Nair SG, Baccala AA Jr, Palyca P, Lash BW, Rizvi MA, Swanson SK, Muina AF, Apolo AB, Iyer G, Rosenberg JE, Teo MY, Bajorin DF. Multicenter Phase II Clinical Trial of Gemcitabine and Cisplatin as Neoadjuvant Chemotherapy for Patients With High-Grade Upper Tract Urothelial Carcinoma. J Clin Oncol. 2023 Mar 10;41(8):1618-1625. doi: 10.1200/JCO.22.00763. Epub 2023 Jan 5.

  PMID: 36603175 DERIVED

• Hird AE, Magee DE, Cheung DC, Sander B, Sridhar S, Nam RK, Kulkarni GS. Neoadjuvant Versus Adjuvant Chemotherapy for Upper Tract Urothelial Carcinoma: A Microsimulation Model. Clin Genitourin Cancer. 2021 Apr;19(2):e135-e147. doi: 10.1016/j.clgc.2020.10.001. Epub 2020 Oct 13.

  PMID: 33168398 DERIVED

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Carcinoma, Transitional Cell

Interventions

Gemcitabine; Cisplatin

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Jonathan Coleman, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 15, 2010
• First Posted: December 16, 2010
• Study Start: December 14, 2010
• Primary Completion: August 6, 2025
• Study Completion: August 6, 2025
• Last Updated: August 8, 2025

Record last verified: 2025-08

Locations

US (9)