UMIN-ICDS Clinical Trial

Public title

A study of the safety and effectiveness of surgery after enfortumab vedotin plus pembrolizumab for stage IV upper urinary tract cancer

Acronym

JUOG-UTUC01 Study

Scientific Title

A Single-Arm, Prospective, Phase II Study on the Safety and Efficacy of Consolidative Surgery after Disease Control with Enfortumab Vedotin and Pembrolizumab in Stage IV Upper Urinary Tract Urothelial Carcinoma

Scientific Title:Acronym

JUOG-UTUC01 Study

Region

Japan

Condition

Stage IV upper urinary tract urothelial carcinoma (renal pelvic or ureteral cancer)

Classification by specialty

Urology

Classification by malignancy

Malignancy

Genomic information

NO

Narrative objectives1

The primary objective of this study is to prospectively evaluate the safety and technical feasibility of consolidative surgery, consisting of radical nephroureterectomy or segmental ureterectomy, for the primary tumor in patients with stage IV upper urinary tract urothelial carcinoma who have achieved disease control with enfortumab vedotin plus pembrolizumab (EVP). Oncological outcomes of this treatment strategy will also be explored in comparison with historical data from patients treated with EVP alone.

Basic objectives2

Safety

Basic objectives -Others

Trial characteristics_1

Confirmatory

Trial characteristics_2

Developmental phase

Phase II

Primary outcomes

Proportion of patients with surgery-related complications of Clavien-Dindo grade 3 or higher within 30 days after surgery.

Events occurring from the end of surgery through postoperative day 30 that are considered related to the surgical procedure or for which a relationship to the surgical procedure cannot be excluded will be included.

Key secondary outcomes

1. Proportion of patients with surgery-related complications of Clavien-Dindo grade 3 or higher within 90 days after surgery
2. Proportion of patients in whom the planned surgery is completed
3. Incidence of intraoperative adverse events assessed using the EAU Intraoperative Adverse Incident Classification
4. R0 resection rate
5. Pathological complete response (pCR) rate
6. Correlation between radiographic tumor shrinkage before surgery and pathological treatment response assessed by Tumor Regression Grade
7. Progression-free survival (PFS)
8. Adjusted PFS rates at 1 and 2 years
9. Overall survival (OS)

Study type

Interventional

Basic design

Single arm

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Uncontrolled

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

1

Purpose of intervention

Treatment

Type of intervention

Maneuver

Interventions/Control_1

Patients with stage IV upper urinary tract urothelial carcinoma who have received enfortumab vedotin plus pembrolizumab (EVP) as standard clinical care and achieved CR, PR, or SD according to RECIST v1.1 will undergo centralized multidisciplinary team (MDT) review for surgical eligibility.

Patients judged eligible for surgery by the central MDT will undergo consolidative surgery for the primary tumor, consisting of radical nephroureterectomy or segmental ureterectomy.

Surgery will generally be performed 4 to 8 weeks after the last dose of EVP. The interval may be extended up to 12 weeks for medical reasons, including recovery from adverse events. Open, laparoscopic, or robot-assisted approaches are permitted. The decision to perform lymph node dissection and its extent will be left to the treating surgeon. Postoperative treatment is not specified by the protocol and will be determined by the treating physician as part of standard clinical care.

Interventions/Control_2

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

20

years-old

<=

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

1. Age 20 years or older at the time of informed consent; both sexes are eligible.
2. Histologically diagnosed upper urinary tract urothelial carcinoma of the renal pelvis or ureter. Tissue biopsy is required in principle; if biopsy is difficult, positive urinary cytology together with imaging findings consistent with upper urinary tract urothelial carcinoma is acceptable.
3. Stage IV disease at initial diagnosis: cT4, cN1-2, or conditionally eligible cM1.
4. Treatment with enfortumab vedotin plus pembrolizumab (EVP) with CR, PR, or SD confirmed according to RECIST v1.1. At least 3 cycles are required in principle; if treatment is interrupted for unavoidable reasons including adverse events, enrollment is permitted if eligibility criteria are met at 9 weeks (63 days) after the first dose.
5. For cM1 disease, metastatic lesions must either achieve CR with EVP or disappear after local treatment such as metastasectomy or radiotherapy, with clinically no evidence of disease maintained for at least 3 months.
6. ECOG Performance Status 0-1.
7. Written informed consent provided by the patient.
8. Consolidative surgery judged feasible by the central multidisciplinary team.

Key exclusion criteria

1. Unresolved grade 3 or higher adverse events related to EVP treatment.
2. Direct invasion of adjacent organs or major blood vessels on imaging such that surgical resection is considered technically infeasible or unsafe.
3. Active synchronous or metachronous malignancy, except malignancies considered adequately controlled and unlikely to affect outcome assessment, including non-muscle-invasive bladder cancer, early prostate cancer, or completely resected basal cell carcinoma of the skin.
4. Pregnant women or women who may be pregnant.
5. Breastfeeding women.
6. Any other condition considered inappropriate for study participation by the investigator.

Target sample size

42

Name of lead principal investigator

1st name	Takashi
Middle name
Last name	Yoshida

Organization

Kansai Medical University

Division name

Department of Urology and Andrology

Zip code

573-1010

Address

2-5-1 Shin-machi, Hirakata, Osaka 573-1010, Japan

TEL

072-804-0101

Email

yoshida.tks@kmu.ac.jp

Name of contact person

1st name	Takashi
Middle name
Last name	Yoshida

Organization

Kansai Medical University

Division name

Department of Urology and Andrology

Zip code

573-1010

Address

2-5-1 Shin-machi, Hirakata, Osaka 573-1010, Japan

TEL

072-804-0101

Homepage URL

Email

yoshida.tks@kmu.ac.jp

Institute

another

Institute

Department

Personal name

Organization

Kansai Medical University

Organization

Division

Category of Funding Organization

Self funding

Nationality of Funding Organization

Japan

Co-sponsor

Name of secondary funder(s)

Organization

Kansai Medical University Hospital Research Ethics Committee

Address

2-5-1 Shin-machi, Hirakata, Osaka 573-1010, Japan

Tel

072-804-0101

Email

rinri@kmu.ac.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

関西医科大学附属病院（大阪府）
関西医科大学総合医療センター（大阪府）
愛知県がんセンター（愛知県）
秋田大学医学部附属病院（秋田県）
愛媛大学医学部附属病院（愛媛県）
大分大学医学部附属病院（大分県）
岡山大学病院（岡山県）
大阪公立大学医学部附属病院（大阪府）
大阪大学医学部附属病院（大阪府）
大阪府済生会野江病院（大阪府）
香川大学医学部附属病院（香川県）
鹿児島大学病院（鹿児島県）
岐阜大学医学部附属病院（岐阜県）
九州大学病院（福岡県）
京都大学医学部附属病院（京都府）
久留米大学病院（福岡県）
神戸大学医学部附属病院（兵庫県）
国立がん研究センター中央病院（東京都）
国立病院機構四国がんセンター（愛媛県）
札幌医科大学附属病院（北海道）
千葉大学医学部附属病院（千葉県）
筑波大学附属病院（茨城県）
東京科学大学病院（東京都）
東京慈恵会医科大学附属柏病院（千葉県）
東京慈恵会医科大学附属病院（東京都）
東北大学病院（宮城県）
鳥取大学医学部附属病院（鳥取県）
富山大学附属病院（富山県）
長崎大学病院（長崎県）
名古屋大学医学部附属病院（愛知県）
奈良県立医科大学附属病院（奈良県）
新潟大学医歯学総合病院（新潟県）
浜松医科大学医学部附属病院（静岡県）
原三信病院（福岡県）
兵庫医科大学病院（兵庫県）
弘前大学医学部附属病院（青森県）
北海道大学病院（北海道）
三重大学医学部附属病院（三重県）
横浜市立大学附属病院（神奈川県）
琉球大学病院（沖縄県）
和歌山県立医科大学附属病院（和歌山県）

Date of disclosure of the study information

2026

Year

10

Month

19

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

Results

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Preinitiation

Date of protocol fixation

2026

Year

09

Month

16

Day

Date of IRB

2026

Year

10

Month

08

Day

Anticipated trial start date

2026

Year

10

Month

30

Day

Last follow-up date

2031

Year

03

Month

31

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

This multicenter prospective phase II study is conducted with approval from the Japan Urological Oncology Group (JUOG).

To ensure objective patient selection and safety, eligibility for consolidative surgery will be centrally reviewed by an independent multidisciplinary team consisting of urologists, medical oncologists, and radiologists.

Enrollment of patients with cN1 disease will be limited to 20. The number of patients with stable disease will be managed with a target of approximately 12 among the total 42 participants. Enrollment of additional patients with stable disease may be temporarily suspended when this number is reached.

For early safety monitoring, an interim safety assessment will be conducted after the first 10 patients have completed surgery and 30 days of postoperative follow-up.

Registered date

2026

Year

10

Month

14

Day

Last modified on

2026

Year

10

Month

14

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000072433