Neoadjuvant Chemotherapy Versus Surgery Alone in Patients With High-Grade Upper Tract Urothelial Carcinoma
Overview
- Phase
- Phase 2
- Intervention
- Radical nephroureterectomy
- Conditions
- High-Grade Upper Tract Urothelial Carcinoma
- Sponsor
- Xiangya Hospital of Central South University
- Enrollment
- 74
- Locations
- 1
- Primary Endpoint
- Disease-free survival (DFS)
- Status
- Completed
- Last Updated
- 3 years ago
Overview
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.
Investigators
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
- •If female of childbearing potential, serum pregnancy test is negative.
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:
Arms & Interventions
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.
Intervention: Radical nephroureterectomy
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.
Intervention: 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.
Intervention: Radical nephroureterectomy
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.
Intervention: 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.
Intervention: Neoadjuvant Chemotherapy
Outcomes
Primary Outcomes
Disease-free survival (DFS)
Time Frame: 3 years
Disease-free survival
Secondary Outcomes
- Objective Response Rate (ORR)(after neoadjuvant chemotherapy completion, assessed up to 4 weeks)
- Overall survival (OS)(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.(Through neoadjuvant chemotherapy completion, assessed up to 4 weeks)
- Number of participants with treatment-related adverse events as assessed by CTCAE v4.0(through study completion, an average of 1 year)