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

Central South University

Status and phase: Completed; Phase 2

Conditions: High-Grade Upper Tract Urothelial Carcinoma

Treatments: Procedure: Distal ureterectomy; Drug: Neoadjuvant Chemotherapy; Procedure: Radical nephroureterectomy

Study type: Interventional

Funder types: Other

Identifiers

NCT02876861

XYURO001

Details and patient eligibility

About

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.

Full 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.

Enrollment: 74 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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74 participants in 2 patient groups

Surgery alone

Active Comparator group

Description:

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.

Treatment:

Procedure: Radical nephroureterectomy

Procedure: Distal ureterectomy

Neoadjuvant chemotherapy and Surgery

Experimental group

Description:

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.

Treatment:

Procedure: Radical nephroureterectomy

Procedure: Distal ureterectomy

Drug: Neoadjuvant Chemotherapy