Treatment Combination of Durvalumab, Tremelimumab and Enfortumab Vedotin or Durvalumab and Enfortumab Vedotin in Patients With Muscle Invasive Bladder Cancer Ineligible to Cisplatin or Who Refuse Cisplatin (VOLGA)

March 21, 2024 updated by: AstraZeneca

A Phase III Randomized, Open-Label, Multicenter Study to Determine the Efficacy and Safety of Durvalumab in Combination With Tremelimumab and Enfortumab Vedotin or Durvalumab in Combination With Enfortumab Vedotin for Perioperative Treatment in Patients Ineligible for Cisplatin or Who Refuse Cisplatin Undergoing Radical Cystectomy for Muscle Invasive Bladder Cancer (VOLGA)

A global phase 3, multicenter, randomized, trial, to Determine the Efficacy and Safety of Durvalumab in combination with Tremelimumab and Enfortumab Vedotin or Durvalumab in combination with Enfortumab vedotin for Perioperative Treatment in Patients Ineligible for Cisplatin or who refuse Cisplantin Undergoing Radical Cystectomy for Muscle Invasive Bladder Cancer.

The goal of the study is to explore the triplet combination of Durvalumab, Tremelimumab and Enfortumab Vedotin in terms of efficacy and safety compared to the current Standard Of Care (SOC).

Volga trial consists of two parts: Safety Run-In and Main Study. In total the study aims to enroll approximately 830 patients, who will receive triplet combination, duplet combination of Durvalumab and Enfortumab vedotin or currently approved SOC in the main trial. In the main part of the trial there is two out of three chances of being on a treatment arm and the treatment is assigned at random by a computer system.

In this trial patients in the two treatment arms will receive either 3 cycles of neoadjuvant Durvalumab + Tremelimumab + Enfortumab Vedotin or Durvalumab + Enfortumab vedotin and after surgery both treatment arms will continue with adjuvant Durvalumab.

Study Overview

Status

Recruiting

Conditions

Muscle Invasive Bladder Cancer

Intervention / Treatment

Detailed Description

Not provided

Study Type

Interventional

Enrollment (Estimated)

830

Phase

Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Name: AstraZeneca Clinical Study Information Center
Phone Number: 1-877-240-9479
Email: information.center@astrazeneca.com

Study Locations

Argentina
- - Berazategui, Argentina, B1884BBF
    - Withdrawn
    - Research Site
  - Buenos Aires, Argentina, C1120AAT
    - Withdrawn
    - Research Site
  - Buenos Aires, Argentina, C1431FWO
    - Recruiting
    - Research Site
  - Caba, Argentina, C1280AEB
    - Recruiting
    - Research Site
  - Caba, Argentina, C1426ANZ
    - Recruiting
    - Research Site
  - Ciudad Autónoma Buenos Aires, Argentina, C1430EFA
    - Withdrawn
    - Research Site
  - Ciudad de Buenos Aires, Argentina, C1419AHL
    - Recruiting
    - Research Site
  - Pergamino, Argentina, B2700CPM
    - Recruiting
    - Research Site
  - Pilar, Argentina, B1629AHJ
    - Recruiting
    - Research Site
  - Rosario, Argentina, S2000KZE
    - Withdrawn
    - Research Site
Austria
- - Graz, Austria, 8036
    - Recruiting
    - Research Site
  - Krems, Austria, 3500
    - Recruiting
    - Research Site
  - Linz, Austria, 4020
    - Recruiting
    - Research Site
  - Salzburg, Austria, 5020
    - Recruiting
    - Research Site
  - Wien, Austria, 1020
    - Recruiting
    - Research Site
  - Wien, Austria, 1140
    - Withdrawn
    - Research Site
  - Wien, Austria, 1090
    - Recruiting
    - Research Site
  - Wiener Neustadt, Austria, 2700
    - Recruiting
    - Research Site
Brazil
- - Barretos, Brazil, 14784-400
    - Recruiting
    - Research Site
  - Curitiba, Brazil, 81520-060
    - Recruiting
    - Research Site
  - Fortaleza, Brazil, 60135-237
    - Recruiting
    - Research Site
  - Porto Alegre, Brazil, 90610-000
    - Recruiting
    - Research Site
  - Porto Alegre, Brazil, 90035-003
    - Recruiting
    - Research Site
  - Porto Alegre, Brazil, 90035-001
    - Recruiting
    - Research Site
  - Porto Alegre, Brazil, 91350200
    - Recruiting
    - Research Site
  - Rio de Janeiro, Brazil, 22250-905
    - Recruiting
    - Research Site
  - Santa Maria, Brazil, 97015-450
    - Recruiting
    - Research Site
  - Santo André, Brazil, 09060-650
    - Recruiting
    - Research Site
  - Sao Paulo, Brazil, 01323-903
    - Recruiting
    - Research Site
  - Sao Paulo, Brazil, 01246-000
    - Recruiting
    - Research Site
  - Săo Paulo, Brazil, 03162-065
    - Recruiting
    - Research Site
  - Uberlândia, Brazil, 38408-150
    - Recruiting
    - Research Site
Canada
- - Quebec, Canada, G1R 2J6
    - Recruiting
    - Research Site
- Alberta
  - Calgary, Alberta, Canada, T2N 4N2
    - Not yet recruiting
    - Research Site
- British Columbia
  - Abbotsford, British Columbia, Canada, V2S 3N5
    - Not yet recruiting
    - Research Site
- Ontario
  - Hamilton, Ontario, Canada, L8V 5C2
    - Withdrawn
    - Research Site
  - Toronto, Ontario, Canada, M4N 3M5
    - Recruiting
    - Research Site
  - Toronto, Ontario, Canada, M5G 2C1
    - Recruiting
    - Research Site
- Quebec
  - Montreal, Quebec, Canada, H4A 3J1
    - Recruiting
    - Research Site
  - Sherbrooke, Quebec, Canada, J1H 5N4
    - Recruiting
    - Research Site
- Saskatchewan
  - Saskatoon, Saskatchewan, Canada, S7N 4H4
    - Not yet recruiting
    - Research Site
Chile
- - Santiago, Chile, 7500653
    - Recruiting
    - Research Site
  - Santiago, Chile, 7500921
    - Recruiting
    - Research Site
Colombia
- - Barranquilla, Colombia, 80001
    - Not yet recruiting
    - Research Site
  - Cali, Colombia, 760043
    - Not yet recruiting
    - Research Site
  - Medellin, Colombia, 050010
    - Withdrawn
    - Research Site
  - Medellín, Colombia, 50025
    - Suspended
    - Research Site
France
- - Amiens, France, 80090
    - Recruiting
    - Research Site
  - Bayonne, France, 64100
    - Recruiting
    - Research Site
  - Bordeaux Cedex, France, 33075
    - Withdrawn
    - Research Site
  - Clermont Ferrand, France, 63011
    - Recruiting
    - Research Site
  - Lille, France, 59000
    - Recruiting
    - Research Site
  - Lyon, France, 69008
    - Recruiting
    - Research Site
  - Marseille, France, 13385
    - Recruiting
    - Research Site
  - Marseille CEDEX, France, 13273
    - Recruiting
    - Research Site
  - Montpellier, France, 34070
    - Recruiting
    - Research Site
  - Nice, France, 06189
    - Recruiting
    - Research Site
  - Pierre Benite, France, 69495
    - Recruiting
    - Research Site
  - Quint-Fonsegrives, France, 31130
    - Recruiting
    - Research Site
  - Rennes, France, 35000
    - Withdrawn
    - Research Site
  - Saint-Priez En Jarez, France, 42270
    - Recruiting
    - Research Site
  - Strasbourg, France, 67091
    - Recruiting
    - Research Site
  - Suresnes Cedex, France, 92151
    - Recruiting
    - Research Site
  - Vandoeuvre les Nancy, France, 54519
    - Recruiting
    - Research Site
Germany
- - Bielefeld, Germany, 33611
    - Recruiting
    - Research Site
  - Bochum, Germany, 44791
    - Recruiting
    - Research Site
  - Düsseldorf, Germany, 40225
    - Recruiting
    - Research Site
  - Giessen, Germany, 35392
    - Recruiting
    - Research Site
  - Halle, Germany, 06120
    - Recruiting
    - Research Site
  - Hannover, Germany, 30559
    - Recruiting
    - Research Site
  - Hannover, Germany, 30625
    - Recruiting
    - Research Site
  - Herne, Germany, 44625
    - Recruiting
    - Research Site
  - Köln, Germany, 50937
    - Recruiting
    - Research Site
  - Magdeburg, Germany, 39120
    - Recruiting
    - Research Site
  - Mainz, Germany, 55131
    - Recruiting
    - Research Site
  - Mannheim, Germany, 68167
    - Recruiting
    - Research Site
  - Muenchen, Germany, 81377
    - Recruiting
    - Research Site
  - München, Germany, 81675
    - Not yet recruiting
    - Research Site
  - Münster, Germany, 48149
    - Recruiting
    - Research Site
  - Regensburg, Germany, 93053
    - Recruiting
    - Research Site
  - Reutlingen, Germany, 72766
    - Recruiting
    - Research Site
  - Ulm, Germany, 89075
    - Recruiting
    - Research Site
Greece
- - Athens, Greece, 11528
    - Recruiting
    - Research Site
  - Athens, Greece, 12462
    - Recruiting
    - Research Site
  - Heraklion, Greece, 71110
    - Recruiting
    - Research Site
  - Maroussi, Athens, Greece, 15125
    - Recruiting
    - Research Site
Hong Kong
- - Shatin, Hong Kong, 00000
    - Recruiting
    - Research Site
Israel
- - Hadera, Israel, 38100
    - Recruiting
    - Research Site
  - Haifa, Israel, 31096
    - Recruiting
    - Research Site
  - Holon, Israel, 58100
    - Withdrawn
    - Research Site
  - Jerusalem, Israel, 9103102
    - Recruiting
    - Research Site
  - Jerusalem, Israel, 9112001
    - Recruiting
    - Research Site
  - Tel Aviv, Israel, 64239
    - Recruiting
    - Research Site
Italy
- - Aviano, Italy, 33081
    - Recruiting
    - Research Site
  - Bari, Italy, 70124
    - Recruiting
    - Research Site
  - Firenze, Italy, 50134
    - Recruiting
    - Research Site
  - Meldola, Italy, 47014
    - Recruiting
    - Research Site
  - Milan, Italy, 20141
    - Recruiting
    - Research Site
  - Milano, Italy, 20132
    - Recruiting
    - Research Site
  - Napoli, Italy, 80131
    - Recruiting
    - Research Site
  - Padova, Italy, 35128
    - Recruiting
    - Research Site
  - Pozzuoli, Italy, 80078
    - Recruiting
    - Research Site
  - Reggio Emilia, Italy, 42100
    - Recruiting
    - Research Site
  - Roma, Italy, 00137
    - Recruiting
    - Research Site
  - Roma, Italy, 00144
    - Recruiting
    - Research Site
  - Roma, Italy, 00128
    - Recruiting
    - Research Site
  - Terni, Italy, 05100
    - Recruiting
    - Research Site
  - Tricase, Italy, 73039
    - Recruiting
    - Research Site
  - Verona, Italy, 37124
    - Recruiting
    - Research Site
Japan
- - Bunkyo-ku, Japan, 113-8431
    - Recruiting
    - Research Site
  - Fukuoka-shi, Japan, 811-1395
    - Recruiting
    - Research Site
  - Hamamatsu-shi, Japan, 431-3192
    - Recruiting
    - Research Site
  - Hirosaki-shi, Japan, 036-8563
    - Recruiting
    - Research Site
  - Ichikawa-shi, Japan, 272-8516
    - Recruiting
    - Research Site
  - Kanazawa-shi, Japan, 920-8641
    - Recruiting
    - Research Site
  - Kashihara-shi, Japan, 634-8522
    - Recruiting
    - Research Site
  - Kita-gun, Japan, 761-0793
    - Recruiting
    - Research Site
  - Kobe-shi, Japan, 650-0017
    - Recruiting
    - Research Site
  - Kumamoto-shi, Japan, 860-0008
    - Recruiting
    - Research Site
  - Matsuyama-shi, Japan, 791-0288
    - Recruiting
    - Research Site
  - Miyazaki-shi, Japan, 889-1692
    - Recruiting
    - Research Site
  - Okayama-shi, Japan, 700-8558
    - Recruiting
    - Research Site
  - Osaka-shi, Japan, 545-8586
    - Recruiting
    - Research Site
  - Osaka-shi, Japan, 541-8567
    - Recruiting
    - Research Site
  - Osakasayama-shi, Japan, 589-8511
    - Recruiting
    - Research Site
  - Shinjuku-ku, Japan, 160-8582
    - Recruiting
    - Research Site
  - Toyama-shi, Japan, 930-0194
    - Recruiting
    - Research Site
  - Tsukuba-shi, Japan, 305-8576
    - Recruiting
    - Research Site
  - Yokohama-shi, Japan, 241-8515
    - Recruiting
    - Research Site
Korea, Republic of
- - Busan, Korea, Republic of, 47392
    - Recruiting
    - Research Site
  - Goyang-si, Korea, Republic of, 10408
    - Recruiting
    - Research Site
  - Incheon, Korea, Republic of, 405-760
    - Recruiting
    - Research Site
  - Seodaemun-gu, Korea, Republic of, 03722
    - Recruiting
    - Research Site
  - Seongnam-si, Korea, Republic of, 13620
    - Recruiting
    - Research Site
  - Seoul, Korea, Republic of, 06591
    - Recruiting
    - Research Site
  - Seoul, Korea, Republic of, 06351
    - Recruiting
    - Research Site
  - Seoul, Korea, Republic of, 03080
    - Recruiting
    - Research Site
  - Seoul, Korea, Republic of, 02841
    - Recruiting
    - Research Site
  - Seoul, Korea, Republic of, 07985
    - Recruiting
    - Research Site
Mexico
- - Colima, Mexico, 28018
    - Recruiting
    - Research Site
  - Monterrey, Mexico, 64000
    - Recruiting
    - Research Site
  - Monterrey, Mexico, 64570
    - Recruiting
    - Research Site
  - Tlalpan, Mexico, 14050
    - Recruiting
    - Research Site
Netherlands
- - Arnhem, Netherlands, 6815 AD
    - Recruiting
    - Research Site
  - Breda, Netherlands, 4818 CK
    - Recruiting
    - Research Site
  - Groningen, Netherlands, 9713 GZ
    - Recruiting
    - Research Site
  - Hilversum, Netherlands, 1313 XZ
    - Withdrawn
    - Research Site
  - Hoofddorp, Netherlands, 2134 TM
    - Recruiting
    - Research Site
  - Leiden, Netherlands, 2333 ZA
    - Recruiting
    - Research Site
  - Utrecht, Netherlands, 3508 GA
    - Recruiting
    - Research Site
Poland
- - Gdańsk, Poland, 80-214
    - Not yet recruiting
    - Research Site
  - Nowa Sol, Poland, 67-106
    - Not yet recruiting
    - Research Site
  - Skórzewo, Poland, 60-185
    - Recruiting
    - Research Site
  - Warszawa, Poland, 02-781
    - Recruiting
    - Research Site
Portugal
- - Braga, Portugal, 4710
    - Recruiting
    - Research Site
  - Coimbra, Portugal, 3000-075
    - Recruiting
    - Research Site
  - Faro, Portugal, 8000-386
    - Recruiting
    - Research Site
  - Lisboa, Portugal, 1350-352
    - Recruiting
    - Research Site
  - Lisboa, Portugal, 1500-458
    - Recruiting
    - Research Site
  - Lisboa, Portugal, 1500-650
    - Recruiting
    - Research Site
  - Lisboa, Portugal, 1649-035
    - Recruiting
    - Research Site
  - Lisbon, Portugal, 1169-050
    - Recruiting
    - Research Site
  - Porto, Portugal, 4200-072
    - Recruiting
    - Research Site
  - Vila Nova de Gaia, Portugal, 4434-502
    - Recruiting
    - Research Site
Russian Federation
- - Ekaterinburg, Russian Federation, 620102
    - Suspended
    - Research Site
  - Nizhniy Novgorod, Russian Federation, 603074
    - Suspended
    - Research Site
  - Novosibirsk, Russian Federation, 630007
    - Suspended
    - Research Site
  - Saint Petersburg, Russian Federation, 193231
    - Suspended
    - Research Site
  - St. Petersburg, Russian Federation, 194354
    - Suspended
    - Research Site
  - Ufa, Russian Federation, 450054
    - Withdrawn
    - Research Site
Serbia
- - Belgrad, Serbia, 11000
    - Recruiting
    - Research Site
  - Belgrade, Serbia, 11000
    - Recruiting
    - Research Site
  - Nis, Serbia, 18000
    - Withdrawn
    - Research Site
  - Sremska Kamenica, Serbia, 21204
    - Recruiting
    - Research Site
Spain
- - Barcelona, Spain, 08041
    - Recruiting
    - Research Site
  - Barcelona, Spain, 08035
    - Recruiting
    - Research Site
  - Barcelona, Spain, 08036
    - Recruiting
    - Research Site
  - Barcelona, Spain, 08208
    - Recruiting
    - Research Site
  - L'Hospitalet de Llobregat, Spain, 08907
    - Recruiting
    - Research Site
  - Las Palmas de Gran Canaria, Spain, 35016
    - Recruiting
    - Research Site
  - Madrid, Spain, 28040
    - Recruiting
    - Research Site
  - Madrid, Spain, 28033
    - Recruiting
    - Research Site
  - Madrid, Spain, 28046
    - Recruiting
    - Research Site
  - Pamplona, Spain, 31008
    - Recruiting
    - Research Site
  - Santander, Spain, 39008
    - Recruiting
    - Research Site
  - Sevilla, Spain, 41009
    - Recruiting
    - Research Site
Taiwan
- - Taichung, Taiwan, 40447
    - Recruiting
    - Research Site
  - Taichung, Taiwan, 40705
    - Recruiting
    - Research Site
  - Tainan, Taiwan, 70403
    - Recruiting
    - Research Site
  - Tainan, Taiwan, 710
    - Recruiting
    - Research Site
  - Taipei, Taiwan, 10048
    - Recruiting
    - Research Site
Thailand
- - Bangkok, Thailand, 10330
    - Recruiting
    - Research Site
  - Dusit, Thailand, 10300
    - Recruiting
    - Research Site
  - Songkhla, Thailand, 90110
    - Recruiting
    - Research Site
Turkey
- - Adana, Turkey, 01060
    - Recruiting
    - Research Site
  - Ankara, Turkey, 06620
    - Recruiting
    - Research Site
  - Ankara, Turkey
    - Recruiting
    - Research Site
  - Ankara, Turkey, 06560
    - Recruiting
    - Research Site
  - Ankara, Turkey, 5000
    - Recruiting
    - Research Site
  - Antalya, Turkey
    - Recruiting
    - Research Site
  - Edirne, Turkey, 22030
    - Recruiting
    - Research Site
  - Istanbul, Turkey, 34722
    - Recruiting
    - Research Site
  - Istanbul, Turkey, 32098
    - Recruiting
    - Research Site
  - Karsiyaka, Turkey, 35575
    - Recruiting
    - Research Site
  - Malatya, Turkey, 44280
    - Recruiting
    - Research Site
Ukraine
- - Dnipro, Ukraine, 49102
    - Suspended
    - Research Site
  - Dnipropetrovsk, Ukraine, 49005
    - Suspended
    - Research Site
  - Kiev, Ukraine, 3022
    - Suspended
    - Research Site
United Kingdom
- - Blackburn, United Kingdom, BB2 3HH
    - Withdrawn
    - Research Site
  - Bristol, United Kingdom, BS2 8ED
    - Withdrawn
    - Research Site
  - Gillingham, United Kingdom, ME7 5NY
    - Not yet recruiting
    - Research Site
  - Glasgow, United Kingdom, G12 0XH
    - Recruiting
    - Research Site
  - London, United Kingdom, EC1A 7BE
    - Recruiting
    - Research Site
  - London, United Kingdom, NW1 2PG
    - Recruiting
    - Research Site
  - Sheffield, United Kingdom, S10 2RX
    - Not yet recruiting
    - Research Site
United States
- Arizona
  - Phoenix, Arizona, United States, 85054
    - Withdrawn
    - Research Site
- California
  - Orange, California, United States, 92868
    - Recruiting
    - Research Site
  - Santa Monica, California, United States, 90404
    - Recruiting
    - Research Site
- Colorado
  - Colorado Springs, Colorado, United States, 80909
    - Recruiting
    - Research Site
- Connecticut
  - New Haven, Connecticut, United States, 06510
    - Recruiting
    - Research Site
- District of Columbia
  - Washington, District of Columbia, United States, 20010
    - Recruiting
    - Research Site
- Florida
  - Fort Myers, Florida, United States, 33901
    - Recruiting
    - Research Site
- Idaho
  - Coeur d'Alene, Idaho, United States, 83814
    - Recruiting
    - Research Site
- Illinois
  - Maywood, Illinois, United States, 60153
    - Recruiting
    - Research Site
- Indiana
  - Indianapolis, Indiana, United States, 46250
    - Recruiting
    - Research Site
- Iowa
  - Iowa City, Iowa, United States, 52242
    - Recruiting
    - Research Site
- Kentucky
  - Louisville, Kentucky, United States, 40207
    - Recruiting
    - Research Site
- Maine
  - Scarborough, Maine, United States, 04074
    - Recruiting
    - Research Site
- Massachusetts
  - Boston, Massachusetts, United States, 02111
    - Not yet recruiting
    - Research Site
- Michigan
  - Brighton, Michigan, United States, 48114
    - Recruiting
    - Research Site
  - Detroit, Michigan, United States, 48202
    - Recruiting
    - Research Site
- Mississippi
  - Jackson, Mississippi, United States, 39213
    - Recruiting
    - Research Site
- Nevada
  - Las Vegas, Nevada, United States, 89102
    - Recruiting
    - Research Site
- New Jersey
  - Saddle Brook, New Jersey, United States, 07663
    - Recruiting
    - Research Site
- New York
  - Albany, New York, United States, 12206
    - Recruiting
    - Research Site
  - Brooklyn, New York, United States, 11219
    - Recruiting
    - Research Site
  - Buffalo, New York, United States, 14263
    - Recruiting
    - Research Site
  - New York, New York, United States, 10040
    - Not yet recruiting
    - Research Site
  - Syracuse, New York, United States, 13210
    - Recruiting
    - Research Site
- Ohio
  - Cincinnati, Ohio, United States, 45219
    - Withdrawn
    - Research Site
  - Columbus, Ohio, United States, 43212
    - Withdrawn
    - Research Site
- Oregon
  - Portland, Oregon, United States, 97239
    - Recruiting
    - Research Site
- Pennsylvania
  - Hershey, Pennsylvania, United States, 17033
    - Recruiting
    - Research Site
  - Pittsburgh, Pennsylvania, United States, 15212
    - Recruiting
    - Research Site
  - Pittsburgh, Pennsylvania, United States, 15240
    - Recruiting
    - Research Site
- Tennessee
  - Knoxville, Tennessee, United States, 37932
    - Recruiting
    - Research Site
  - Memphis, Tennessee, United States, 38103
    - Not yet recruiting
    - Research Site
- Texas
  - Austin, Texas, United States, 78731
    - Recruiting
    - Research Site
  - Dallas, Texas, United States, 75246
    - Recruiting
    - Research Site
  - Fort Worth, Texas, United States, 76104
    - Recruiting
    - Research Site
  - Houston, Texas, United States, 77030
    - Recruiting
    - Research Site
  - Irving, Texas, United States, 75063
    - Recruiting
    - Research Site
- Virginia
  - Norfolk, Virginia, United States, 23502
    - Recruiting
    - Research Site
- Washington
  - Spokane, Washington, United States, 99208
    - Recruiting
    - Research Site
  - Tacoma, Washington, United States, 98405
    - Recruiting
    - Research Site
Vietnam
- - Ha Noi, Vietnam, 100000
    - Recruiting
    - Research Site
  - Hanoi, Vietnam, 100000
    - Recruiting
    - Research Site
  - Ho Chi Minh, Vietnam, 700000
    - Recruiting
    - Research Site
  - Ho Chi Minh city, Vietnam, 700000
    - Withdrawn
    - Research Site
  - Hue, Vietnam, 530000
    - Recruiting
    - Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 130 years (Adult, Older Adult)

Accepts Healthy Volunteers

Description

Inclusion Criteria:

Histologically or cytologically documented muscle-invasive UC of the bladder.
Participants with transitional cell and mixed transitional/non-transitional cell histologies;
Participants with MIBC clinical tumor (T) stage T2-T4aN0/1M0 or UC of the bladder with clinical state T1N1M0.
Participants should also have not received prior systemic chemotherapy or immunotherapy for the treatment of MIBC or bladder UC.
Medically fit for cystectomy and able to receive neoadjuvant therapy;
Patients who have not received prior systemic chemotherapy or immunotherapy for treatment of MIBC;
ECOG performance status of 0,1,2 at enrollment.
Availability of tumor sample prior to study entry;
Must have a life expectancy of at least 12 weeks at randomization.
Cisplatin-ineligible, as defined by any of the following criteria (based on Galsky et al 2011) OR Refuse cisplatin based chemotherapy (must be documented in the medical records)

Exclusion criteria:

Evidence of lymph node (N2+) or metastatic TCC/UC disease at the time of screening.
Active infection
Uncontrolled intercurrent illness
Prior exposure to immune-mediated therapy (with exclusion of Bacillus-Calmette Guerin [BCG]), including but not limited to other anti-CTLA-4, anti--PD-1, anti PD-L1, or anti-PD-L2 antibodies.
Current or prior use of immunosuppressive medication within 14 days before the first dose of IPs.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Interventional Model: Parallel Assignment
Masking: None (Open Label)

Number of Arms

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Durvalumab + Tremelimumab + Enfortumab vedotin Participants will receive 3 preoperative 21-day cycles of Durvalumab + Tremelimumab + Enfortumab Vedotin, followed by radical cystectomy, followed by 1 cycle of postoperative Tremelimumab and 9 cycles of Durvalumab. Each postoperative cycle is 28 days.	Drug: Durvalumab Anti- PD-L1 Antibody Other Names: MEDI4736 IMFINZI Drug: Tremelimumab Human IgG2 mAb Drug: Enfortumab Vedotin Nectin-4-directed antibody and microtubule inhibitor conjugate Other Names: PADCEV Procedure: Radical Cystectomy For cisplatin-ineligible or cisplatin-refusal patients
Experimental: Durvalumab + Enfortumab vedotin Participants will receive 3 preoperative 21-day cycles of Durvalumab + Enfortumab Vedotin, followed by radical cystectomy, followed by 9 cycles of Durvalumab. Each postoperative cycle is 28 days.	Drug: Durvalumab Anti- PD-L1 Antibody Other Names: MEDI4736 IMFINZI Drug: Enfortumab Vedotin Nectin-4-directed antibody and microtubule inhibitor conjugate Other Names: PADCEV Procedure: Radical Cystectomy For cisplatin-ineligible or cisplatin-refusal patients
Active Comparator: Cystectomy with or without approved Adjuvant Therapy. Participants may receive SoC (nivolumab approved as adjuvant treatment for MIBC based on high risk criteria) per approved label in the country OR Participants receive standard of care surgery (radical cystectomy) alone.	Procedure: Radical Cystectomy For cisplatin-ineligible or cisplatin-refusal patients

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compare efficacy of durvalumab + tremelimumab + EV relative to cystectomy alone on pCR rate (Safety Run-In and Main Study) Time Frame: Up to 3 years	Pathologic complete response (pCR) rate is defined as the number of participants whose pathological staging was T0N0M0 as assessed per central pathological review using specimens obtained via cystectomy, up to 3 years.	Up to 3 years
Compare efficacy of durvalumab + tremelimumab + EV relative to cystectomy alone on EFS (Safety Run-In and Main Study) Time Frame: Up to 3 years	Event-free survival (EFS;) is defined as the time from randomization to the first occurrence of any of the following events: recurrence of disease post-radical cystectomy, the first documented progression in participants who did not receive radical cystectomy, failure to undergo radical cystectomy in participants with residual disease, or death due to any cause, up to 3 years.	Up to 3 years
Safety and Tolerability as evaluated by adverse events occurring throughout the study (Safety Run-In part) Time Frame: At completion of study treatment by the last patient and at 3 months.	Frequency of Adverse Events.	At completion of study treatment by the last patient and at 3 months.
Safety and tolerability of durvalumab + tremelimumab + EV in participants with MIBC who are ineligible for cisplatin or who refuse cisplatin as assessed by vital signs (blood pressure in mmHg) (Safety Run-In part) Time Frame: Up to 84 months		Up to 84 months
Safety and tolerability of durvalumab + tremelimumab + EV in participants with MIBC who are ineligible for cisplatin or who refuse cisplatin as assessed by vital signs (pulse rate) in beats per minute (Safety Run-In part) Time Frame: Up to 84 months		Up to 84 months
Safety and tolerability of durvalumab + tremelimumab + EV in participants with MIBC who are ineligible for cisplatin or who refuse cisplatin as assessed by vital signs (respiration rate) in breaths per minute (Safety Run-In part) Time Frame: Up to 84 months		Up to 84 months
Safety and tolerability of durvalumab + tremelimumab + EV in participants with MIBC who are ineligible for cisplatin or who refuse cisplatin as assessed by vital signs (temperature) in degrees Celsius (Safety Run-In part) Time Frame: Up to 84 months		Up to 84 months
Safety and tolerability of durvalumab + tremelimumab + EV in participants with MIBC who are ineligible for cisplatin or who refuse cisplatin s assessed by abnormality in clinical chemistry by liver function (Safety Run-In part) Time Frame: Up to 84 months	Clinical chemistry will be assessed by liver function assessment (ALT, AST, albumin, total bilirubin measured in units per dL)	Up to 84 months
Safety and tolerability of durvalumab + tremelimumab + EV in participants with MIBC who are ineligible for cisplatin or who refuse cisplatin as assessed by abnormality in clinical chemistry by kidney function (Safety Run-In part) Time Frame: Up to 84 months	Clinical chemistry will be assessed by kidney function assessment in mg/dL	Up to 84 months
Safety and tolerability of durvalumab + tremelimumab + EV in participants with MIBC who are ineligible for cisplatin or who refuse cisplatin as assessed by abnormality in clinical chemistry by thyroid function (Safety Run-In part) Time Frame: Up to 84 months	Clinical chemistry will be assessed by thyroid function assessment in units per mL.	Up to 84 months
Safety and tolerability of durvalumab + tremelimumab + EV in participants with MIBC who are ineligible for cisplatin or who refuse cisplatin as assessed by abnormality in haematology (Safety Run-In part) Time Frame: Up to 84 months	Hematology will be assessed by white cell count, platelet count, absolute neutrophil count and absolute lymphocyte count.	Up to 84 months
Safety and tolerability of durvalumab + tremelimumab + EV in participants with MIBC who are ineligible for cisplatin or who refuse cisplatin as assessed by ECG (pulse rate) (Safety Run-In part) Time Frame: Up to 84 months		Up to 84 months
Changes in WHO/ECOG performance status (Safety Run-In part) Time Frame: Up to 84 months	Eastern Cooperative Oncology Group (ECOG) performance status scale range 0 to 5, where 0 is fully active, able to carry on all pre disease performance without restriction - best outcome and 5 -death - worst outcome.	Up to 84 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1.Pathologic complete response (pCR) rates at time of cystectomy in Arm 2 vs Arm 3 (Safety Run-In and Main Study) Time Frame: 3 years	Pathologic complete response (pCR) rate is defined as the number of participants whose pathological staging was T0N0M0 as assessed per central pathological review using specimens obtained via cystectomy, at 3 years.	3 years
2.Event-free survival (EFS) defined as time from randomization to event in Arm 2 vs Arm 3 (Safety Run-In and Main Study) Time Frame: Up to 5 years	Event-free survival (EFS;) is defined as the time from randomization to the first occurrence of any of the following events: recurrence of disease post-radical cystectomy, the first documented progression in participants who did not receive radical cystectomy, failure to undergo radical cystectomy in participants with residual disease, or death due to any cause, up to 5 years.	Up to 5 years
3.Overall survival (Main Study part) Time Frame: Up to 5 years	Overall Survival is defined as length of time from randomization until the date of death due to any cause, whichever came first, assessed up to 5 years.	Up to 5 years
4.EFS at 24 months (EFS24) (Main Study part) Time Frame: Up to 24 months	EFS24 is defined as proportion of participants alive and event-free at 24 months	Up to 24 months
5.Overall survival rate at 5 years (Main Study part) Time Frame: At 5 years	The proportion of participants alive at 5 years (OS5) is defined as the Kaplan-Meier estimate of OS at 5 years after randomization	At 5 years
6.Disease-free survival (DFS) (Main Study part) Time Frame: Up to first recurrence of disease or death up to 5 years	DFS is defined as time from radical cystectomy to recurrence or death, whichever came first, assessed up to 5 years.	Up to first recurrence of disease or death up to 5 years
7.Pathologic downstaging (pDS) rate-to < pT2 (Main Study part) Time Frame: 3 years	pDS rate is defined as the rate of downstaging to < pT2, including pT0, pTis, pTa, pT1, and N0	3 years
8.Disease-specific survival (DSS) (Main Study part) Time Frame: from randomization until death due to bladder cancer up to 5 year.	DSS is defined as time from randomization until death due to bladder cancer, assessed up to 5 years.	from randomization until death due to bladder cancer up to 5 year.
9.EORTC QLQ-C30 European Organisation for Research and Treatment of Cancer 30-item Core Quality of Life Questionnaire) (Main Study part) Time Frame: from baseline and time to definitive clinically, assessed up to 5 years		from baseline and time to definitive clinically, assessed up to 5 years
10.Immunogenicity of durvalumab when used in combination with Tremelimumab as measured by presence of antidrug antibodies (ADA) (Main Study part) Time Frame: At 3 months after last dose of durvalumab and tremelimumab		At 3 months after last dose of durvalumab and tremelimumab
11.Area under the Plasma Concentration versus Time Curve (AUCτ) of durvalumab and tremelimumab (Main Study part) Time Frame: At 3 months after last dose of durvalumab and tremelimumab		At 3 months after last dose of durvalumab and tremelimumab
11.Time to maximum observed serum concentration (tmax) of durvalumab and tremelimumab (Main Study part) Time Frame: At 3 months after last dose of durvalumab and tremelimumab		At 3 months after last dose of durvalumab and tremelimumab
12. Metastasis-free survival (MFS) (Main Study part) Time Frame: From randomization until the first recognition of distant metastases or death, up to approximately 48 months.	MFS is defined as the time from date of randomization until the first recognition of distant metastases or death, whichever occurs first, up to approximately 48 months.	From randomization until the first recognition of distant metastases or death, up to approximately 48 months.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AstraZeneca

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 5, 2021

Primary Completion (Estimated)

July 18, 2025

Study Completion (Estimated)

September 8, 2028

Study Registration Dates

First Submitted

June 17, 2021

First Submitted That Met QC Criteria

July 2, 2021

First Posted (Actual)

July 14, 2021

Study Record Updates

Last Update Posted (Actual)

March 22, 2024

Last Update Submitted That Met QC Criteria

March 21, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

D910PC00001
2020-005452-38 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

IPD Sharing Time Frame

AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

IPD Sharing Access Criteria

When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

IPD Sharing Supporting Information Type

STUDY_PROTOCOL
SAP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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Study Overview

Status

Conditions

Intervention / Treatment

Detailed Description

Study Type

Enrollment (Estimated)

Phase

Contacts and Locations

Study Contact

Study Locations

Participation Criteria

Eligibility Criteria

Ages Eligible for Study

Accepts Healthy Volunteers

Description

Study Plan

How is the study designed?

Design Details

Number of Arms

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure

Measure Description

Time Frame

Secondary Outcome Measures

Outcome Measure

Measure Description

Time Frame

Collaborators and Investigators

Sponsor

Study record dates

Study Major Dates

Study Start (Actual)

Primary Completion (Estimated)

Study Completion (Estimated)

Study Registration Dates

First Submitted

First Submitted That Met QC Criteria

First Posted (Actual)

Study Record Updates

Last Update Posted (Actual)

Last Update Submitted That Met QC Criteria

Last Verified

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

IPD Plan Description

IPD Sharing Time Frame

IPD Sharing Access Criteria

IPD Sharing Supporting Information Type

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Studies a U.S. FDA-regulated device product

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Clinical Trials on Durvalumab

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