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

NCT02876861 | Completed Phase 2 DMC

• 1 other identifier: XYURO001
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 1

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.

Conditions

High-Grade Upper Tract Urothelial Carcinoma

Keywords

Neoadjuvant chemotherapy; upper tract urothelial carcinoma

Outcome Measures

Primary Outcomes (1)

• Disease-free survival (DFS)

  Disease-free survival

  3 years

Secondary Outcomes (4)

• 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

Study Arms (2)

Surgery alone

ACTIVE COMPARATOR

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; Procedure: Distal ureterectomy

Neoadjuvant chemotherapy and Surgery

EXPERIMENTAL

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; Procedure: Distal ureterectomy; Drug: Neoadjuvant Chemotherapy

Interventions

Radical nephroureterectomy PROCEDURE

Radical nephroureterectomy (RNU) with an ipsilateral bladder cuff

Neoadjuvant chemotherapy and Surgery; Surgery alone

Distal ureterectomy PROCEDURE

Distal ureterectomy.

Neoadjuvant chemotherapy and Surgery; Surgery alone

Neoadjuvant Chemotherapy DRUG

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

Also known as: GC

Neoadjuvant chemotherapy and Surgery

Eligibility Criteria

• Age: 18 Years - 80 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. 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

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 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.

Sponsors & Collaborators

• Xiangya Hospital of Central South University: lead
• Central South University: collaborator
• The Third Xiangya Hospital of Central South University: collaborator
• Hunan Cancer Hospital: collaborator
• Hunan Provincial People's Hospital: collaborator

Study Sites (1)

Xiangya Hospital of Central South Univeristy

Changsha, Hunan, 410008, China

Location

MeSH Terms

Interventions

Neoadjuvant Therapy

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics

Study Officials

• Long Wang, M.D. Ph.D.

  Xiangya Hospital of Central South University

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: August 14, 2016
• First Posted: August 24, 2016
• Study Start: February 1, 2014
• Primary Completion: August 1, 2022
• Study Completion: August 1, 2022
• Last Updated: November 10, 2022

Record last verified: 2022-06

Locations

CN (1)