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

NCT ID: NCT02876861

Last Updated: 2022-11-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 74 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-02-28
• Study Completion Date: 2022-08-31

Brief Summary

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.

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.

Conditions

High-Grade Upper Tract Urothelial Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Radical nephroureterectomy

Intervention Type: PROCEDURE

Radical nephroureterectomy (RNU) with an ipsilateral bladder cuff

Distal ureterectomy

Intervention Type: PROCEDURE

Distal ureterectomy.

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.

Group Type: EXPERIMENTAL

Radical nephroureterectomy

Intervention Type: PROCEDURE

Radical nephroureterectomy (RNU) with an ipsilateral bladder cuff

Distal ureterectomy

Intervention Type: PROCEDURE

Distal ureterectomy.

Neoadjuvant Chemotherapy

Intervention Type: DRUG

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

Interventions

Radical nephroureterectomy

Radical nephroureterectomy (RNU) with an ipsilateral bladder cuff

Intervention Type: PROCEDURE

Distal ureterectomy

Distal ureterectomy.

Intervention Type: PROCEDURE

Neoadjuvant Chemotherapy

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

Intervention Type: DRUG

Other Intervention Names

GC

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Central South University

OTHER

Sponsor Role: collaborator

The Third Xiangya Hospital of Central South University

OTHER

Sponsor Role: collaborator

Hunan Cancer Hospital

OTHER

Sponsor Role: collaborator

Hunan Provincial People's Hospital

OTHER

Sponsor Role: collaborator

Xiangya Hospital of Central South University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Long Wang, M.D. Ph.D.

Role: STUDY_CHAIR

Xiangya Hospital of Central South University

Locations

Xiangya Hospital of Central South Univeristy

Changsha, Hunan, China

Countries

China

Other Identifiers

XYURO001

Identifier Type: -

Identifier Source: org_study_id