Neoadjuvant Chemotherapy Versus Surgery Alone in Patients With High-Grade UTUC

November 7, 2022 updated by: Xiangya Hospital of Central South University

Neoadjuvant Chemotherapy Versus Surgery Alone in Patients With High-Grade Upper Tract Urothelial Carcinoma

The purpose of this study is to see if getting chemotherapy with Gemcitabine and Cisplatin (GC) for 2-4 cycles can help shrink the tumor before undergoing surgery and improves the overall survival for high-grade upper tract urothelial carcinoma.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The purpose of this study is to see if getting chemotherapy with Gemcitabine and Cisplatin (Gemcitabine, 1250mg/m2, d1 d8, Cisplatin, 75mg/m2, d1-d3, 21d, 2-4 cycles) for 2-4 cycles can help shrink the tumor before undergoing surgery and improves the overall survival for high-grade upper tract urothelial carcinoma.

Study Type

Interventional

Enrollment (Actual)

74

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Hunan
      • Changsha, Hunan, China, 410008
        • Xiangya Hospital of Central South Univeristy

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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. Hydronephrosis associated with tumor on imaging or 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 ≤ 1.5 Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x ULN for the institution Alkaline phosphatase ≤ 2.5 x upper limit of normal (ULN) for the institution Serum creatinine ≤ 1.5 mg/dL and calculated creatinine clearance ≥ 55 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: Chronic kidney disease (CKD) epi : glomerular filtration rate (GFR) = 141 X min(Scr/κ,1)α X max(Scr/κ,1)-1.209 X 0.993 Age 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.
  • 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

Exclusion Criteria:

  • 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 New York Heart Association (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.
  • Ongoing treatment with therapeutic doses of warfarin or low molecular weight heparin (low dose warfarin up to 2 mg po daily or use of subcutaneous low molecular weight heparin for thromboembolic prophylaxis is allowed).
  • Pregnancy or breast-feeding. Patients must be surgically sterile or be postmenopausal, or must agree to use effective contraception during the period of therapy. The definition of effective contraception will be based on the judgment of the MSKCC and participating site PI. Male patients must be surgically sterile or agree to use effective contraception

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Surgery alone

Surgeons: the operation shall be performed by senior urologic surgeons. Try to achieve the consistency of operation quality.

Operation: Radical nephroureterectomy (RNU) with an ipsilateral bladder cuff or distal ureterectomy.
Procedure: Radical nephroureterectomy
Radical nephroureterectomy (RNU) with an ipsilateral bladder cuff
Procedure: Distal ureterectomy
Distal ureterectomy.
Experimental: Neoadjuvant chemotherapy and Surgery

Experimental: Neoadjuvant chemotherapy group

Neoadjuvant chemotherapy(Gemcitabine and Cisplatin):

Gemcitabine, 1250mg/m2, d1 d8, Cisplatin, 75mg/m2, d1-d3, 21d, 2-4 cycles.

Surgery:

2-3weeks after Neoadjuvant chemotherapy

Surgeons: the operation shall be performed by senior urologic surgeons. Try to achieve the consistency of operation quality.

Operation: Radical nephroureterectomy (RNU) with an ipsilateral bladder cuff or distal ureterectomy.
Procedure: Radical nephroureterectomy
Radical nephroureterectomy (RNU) with an ipsilateral bladder cuff
Procedure: Distal ureterectomy
Distal ureterectomy.
Drug: Neoadjuvant Chemotherapy
Gemcitabine, 1250mg/m2, d1 d8, Cisplatin, 75mg/m2, d1-d3, 21d, 2-4 cycles.
Other Names:
  • GC

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease-free survival (DFS)
Time Frame: 3 years
Disease-free survival
3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate (ORR)
Time Frame: after neoadjuvant chemotherapy completion, assessed up to 4 weeks
ORR is defined as the percentage of subjects with evidence of a confirmed complete response (CR) or partial response (PR) as per Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1
after neoadjuvant chemotherapy completion, assessed up to 4 weeks
Overall survival (OS)
Time Frame: From date of surgery until the date of first documented recurrence or date of death from any cause, whichever came first, assessed up to 100 months death from any cause, whichever came first, assessed up to 100 months
Overall survival
From date of surgery until the date of first documented recurrence or date of death from any cause, whichever came first, assessed up to 100 months death from any cause, whichever came first, assessed up to 100 months
Number of participants with chemotherapy-related adverse events as assessed by National Cancer Institute Common Toxicity Criteria version 4.0.
Time Frame: Through neoadjuvant chemotherapy completion, assessed up to 4 weeks
Number of participants with chemotherapy-related adverse events as assessed by National Cancer Institute Common Toxicity Criteria version 4.0.
Through neoadjuvant chemotherapy completion, assessed up to 4 weeks
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time Frame: through study completion, an average of 1 year
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
through study completion, an average of 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Xiangya Hospital of Central South University

Collaborators

Hunan Cancer Hospital
The Third Xiangya Hospital of Central South University
Hunan Provincial People's Hospital
Central South University

Investigators

  • Study Chair: Long Wang, M.D. Ph.D., Xiangya Hospital of Central South University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2014

Primary Completion (Actual)

August 1, 2022

Study Completion (Actual)

August 1, 2022

Study Registration Dates

First Submitted

August 14, 2016

First Submitted That Met QC Criteria

August 18, 2016

First Posted (Estimate)

August 24, 2016

Study Record Updates

Last Update Posted (Actual)

November 10, 2022

Last Update Submitted That Met QC Criteria

November 7, 2022

Last Verified

June 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • XYURO001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on High-Grade Upper Tract Urothelial Carcinoma

Clinical Trials on Radical nephroureterectomy

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Albania

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe