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
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)
2 other identifiers
interventional
712
25 countries
202
Brief Summary
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 Cisplatin based chemotherapy 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 or the duplet combination of Durvalumab 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 677 patients, who will receive triplet combination, duplet combination or currently approved SOC in the main study. 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 + Enfortumab Vedotin and 2 cycles of Tremelimumab or Durvalumab + Enfortumab vedotin and after surgery both treatment arms will receive either adjuvant Durvalumab or adjuvant Durvalumab and 1 cycle of Tremelimumab.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Aug 2021
Longer than P75 for phase_3
202 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 17, 2021
CompletedFirst Posted
Study publicly available on registry
July 14, 2021
CompletedStudy Start
First participant enrolled
August 5, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 30, 2026
CompletedStudy Completion
Last participant's last visit for all outcomes
September 8, 2028
ExpectedApril 14, 2026
April 1, 2026
4.7 years
June 17, 2021
April 13, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (12)
To assess the safety and tolerability as evaluated by adverse events occurring throughout the study (Safety Run-In part)
Frequency of Adverse Events.
At completion of study treatment by the last patient and at 3 months.
To assess the safety and tolerability of durvalumab + tremelimumab + EV in participants with MIBC who are ineligible for cisplatin as assessed by vital signs (blood pressure in mmHg) (Safety Run-In part)
Up to 84 months
To assess the safety and tolerability of durvalumab + tremelimumab + EV in participants with MIBC who are ineligible for cisplatin as assessed by vital signs (pulse rate) in beats per minute (Safety Run-In part)
Up to 84 months
To assess the safety and tolerability of durvalumab + tremelimumab + EV in participants with MIBC who are ineligible for cisplatin as assessed by vital signs (respiration rate) in breaths per minute (Safety Run-In part)
Up to 84 months
To assess the safety and tolerability of durvalumab + tremelimumab + EV in participants with MIBC who are ineligible for cisplatin as assessed by vital signs (temperature) in degrees Celsius (Safety Run-In part)
Up to 84 months
To assess the safety and tolerability of durvalumab + tremelimumab + EV in participants with MIBC who are ineligible for cisplatin as assessed by abnormality in clinical chemistry by liver function (Safety Run-In part)
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)
Clinical chemistry will be assessed by kidney function assessment in mg/dL
Up to 84 months
To assess the safety and tolerability of durvalumab + tremelimumab + EV in participants with MIBC who are ineligible for cisplatin as assessed by abnormality in clinical chemistry by thyroid function (Safety Run-In part)
Clinical chemistry will be assessed by thyroid function assessment in units per mL.
Up to 84 months
To assess the safety and tolerability of durvalumab + tremelimumab + EV in participants with MIBC who are ineligible for cisplatin as assessed by abnormality in haematology (Safety Run-In part)
Hematology will be assessed by white cell count, platelet count, absolute neutrophil count and absolute lymphocyte count.
Up to 84 months
To assess the safety and tolerability of durvalumab + tremelimumab + EV in participants with MIBC who are ineligible for cisplatin as as assessed by ECG (pulse rate) (Safety Run-In part)
Up to 84 months
Changes in WHO/ECOG performance status (Safety Run-In part)
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
Compare efficacy of durvalumab + tremelimumab + EV (Arm 1) relative to cystectomy (Arm 3) and durvalumab + EV (Arm 2) relative to cystectomy (Arm 3) on EFS (Main Study)
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
Secondary Outcomes (13)
1. To evaluate the efficacy of durvalumab + tremelimumab + EV on pCR rate (Safety Run-in part)
3 years
2. To evaluate the efficacy of durvalumab + tremelimumab + EV on EFS (Safety Run-in part)
3 years
3. Pathologic complete response (pCR) rates at time of cystectomy in Arm1 vs Arm3 and Arm 2 vs Arm 3 (Main Study part)
3 years
4. Overall survival (Safety Run-in and Main Study part)
Up to 5 years
5. EFS at 24 months (EFS24) (Safety Run-in and Main Study part)
Up to 24 months
- +8 more secondary outcomes
Study Arms (3)
Durvalumab + Tremelimumab + Enfortumab Vedotin
EXPERIMENTALParticipants will receive 3 preoperative 21-day cycles of Durvalumab + Enfortumab Vedotin and 2 cycles of Tremelimumab, followed by radical cystectomy, followed by 1 cycle of postoperative Tremelimumab and 9 cycles of Durvalumab. Each postoperative cycle is 28 days.
Durvalumab + Enfortumab vedotin
EXPERIMENTALParticipants 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.
Cystectomy with or without approved Adjuvant Therapy.
ACTIVE COMPARATORParticipants 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.
Interventions
Anti- PD-L1 Antibody
Nectin-4-directed antibody and microtubule inhibitor conjugate
For cisplatin-ineligible or cisplatin-refusal patients
Eligibility Criteria
You may qualify if:
- 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 with T1 stage are allowed only with N1 disease)
- 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, following criteria based on Galsky et al 2011 OR Refuse cisplatin based chemotherapy (must be documented in the medical records)
You may not qualify if:
- Evidence of lymph node (N2+) or metastatic TCC/UC disease at the time of screening.
- Active infection
- Uncontrolled intercurrent illness
- Current or prior use of immunosuppressive medication within 14 days before the first dose of IPs.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AstraZenecalead
Study Sites (202)
Research Site
Orange, California, 92868, United States
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Santa Monica, California, 90404, United States
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New Haven, Connecticut, 06510, United States
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Washington D.C., District of Columbia, 20010, United States
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Fort Myers, Florida, 33901, United States
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Coeur d'Alene, Idaho, 83814, United States
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Maywood, Illinois, 60153, United States
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Indianapolis, Indiana, 46250, United States
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Iowa City, Iowa, 52242, United States
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Louisville, Kentucky, 40207, United States
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Scarborough, Maine, 04074, United States
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Boston, Massachusetts, 02111, United States
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Brighton, Michigan, 48114, United States
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Jackson, Mississippi, 39213, United States
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Las Vegas, Nevada, 89102, United States
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Saddle Brook, New Jersey, 07663, United States
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Brooklyn, New York, 11219, United States
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Buffalo, New York, 14263, United States
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New York, New York, 10040, United States
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Syracuse, New York, 13210, United States
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Portland, Oregon, 97239, United States
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Hershey, Pennsylvania, 17033, United States
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Pittsburgh, Pennsylvania, 15212, United States
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Knoxville, Tennessee, 37932, United States
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Austin, Texas, 78731, United States
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Dallas, Texas, 75246, United States
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Fort Worth, Texas, 76104, United States
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Houston, Texas, 77030, United States
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Irving, Texas, 75063, United States
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Norfolk, Virginia, 23502, United States
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Spokane, Washington, 99208, United States
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Buenos Aires, C1431FWO, Argentina
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CABA, C1426ANZ, Argentina
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Ciudad de Buenos Aires, C1280AEB, Argentina
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Ciudad de Buenos Aires, C1419AHL, Argentina
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Pergamino, B2700CPM, Argentina
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Pilar, B1629AHJ, Argentina
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Graz, 8036, Austria
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Krems, 3500, Austria
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Linz, 4020, Austria
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Salzburg, 5020, Austria
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Vienna, 1020, Austria
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Vienna, 1090, Austria
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Wiener Neustadt, 2700, Austria
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Barretos, 14784-400, Brazil
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Curitiba, 81520-060, Brazil
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Fortaleza, 60135-237, Brazil
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Porto Alegre, 90035-001, Brazil
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Porto Alegre, 90035-003, Brazil
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Porto Alegre, 90610-000, Brazil
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Porto Alegre, 91350-200, Brazil
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Rio de Janeiro, 22250-905, Brazil
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Santa Maria, 97015-450, Brazil
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Santo André, 09060-870, Brazil
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São Paulo, 01246-000, Brazil
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São Paulo, 01323-903, Brazil
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Săo Paulo, 03162-065, Brazil
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Uberlândia, 38408-150, Brazil
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Abbotsford British Columbia, British Columbia, V2S 3N5, Canada
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Toronto, Ontario, M4N 3M5, Canada
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Québec, Quebec, G1R 2J6, Canada
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Sherbrooke, Quebec, J1H 5N4, Canada
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Santiago, 7500653, Chile
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Santiago, 7500921, Chile
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Amiens, 80090, France
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Bayonne, 64100, France
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Clermont-Ferrand, 63011, France
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Lille, 59000, France
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Lyon, 69008, France
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Marseille, 13273, France
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Marseille, 13385, France
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Montpellier, 34070, France
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Nice, 06189, France
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Pierre-Bénite, 69495, France
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Quint-Fonsegrives, 31130, France
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Saint-Priez En Jarez, 42270, France
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Strasbourg, 67091, France
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Suresnes, 92151, France
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Vandœuvre-lès-Nancy, 54519, France
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Bielefeld, 33611, Germany
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Bochum, 44791, Germany
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Cologne, 50937, Germany
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Düsseldorf, 40225, Germany
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Giessen, 35392, Germany
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Hanover, 30625, Germany
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Herne, 44625, Germany
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Magdeburg, 39120, Germany
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Mainz, 55131, Germany
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Mannheim, 68167, Germany
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München, 81377, Germany
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Münster, 48149, Germany
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Regensburg, 93053, Germany
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Reutlingen, 72766, Germany
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Ulm, 89075, Germany
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Athens, 11528, Greece
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Athens, 12462, Greece
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Maroussi, Athens, 15125, Greece
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Shatin, 00000, Hong Kong
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Hadera, 38100, Israel
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Haifa, 31096, Israel
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Jerusalem, 9103102, Israel
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Jerusalem, 9112001, Israel
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Tel Aviv, 64239, Israel
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Bari, 70124, Italy
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Florence, 50134, Italy
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Meldola, 47014, Italy
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Milan, 20132, Italy
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Milan, 20141, Italy
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Padova, 35128, Italy
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Pozzuoli, 80078, Italy
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Reggio Emilia, 42100, Italy
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Roma, 00128, Italy
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Roma, 00137, Italy
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Roma, 00144, Italy
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Terni, 05100, Italy
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Tricase, 73039, Italy
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Verona, 37124, Italy
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Bunkyō City, 113-8431, Japan
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Fukuoka, 811-1395, Japan
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Hamamatsu, 431-3192, Japan
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Ichikawa-shi, 272-8516, Japan
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Kanazawa, 920-8641, Japan
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Kashihara-shi, 634-8522, Japan
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Kawasaki-shi, 216-8511, Japan
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Kita-gun, 761-0793, Japan
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Kobe, 650-0017, Japan
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Kumamoto, 860-0008, Japan
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Matsuyama, 791-0288, Japan
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Miyazaki, 889-1692, Japan
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Niigata, 951-8566, Japan
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Okayama, 700-8558, Japan
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Osaka, 541-8567, Japan
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Osaka, 545-8586, Japan
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Osakasayama-shi, 589-8511, Japan
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Toyama, 930-0194, Japan
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Tsukuba, 305-8576, Japan
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Yokohama, 241-8515, Japan
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Colima, 28018, Mexico
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Monterrey, 64000, Mexico
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Arnhem, 6815 AD, Netherlands
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Breda, 4818 CK, Netherlands
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Groningen, 9713 GZ, Netherlands
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Hoofddorp, 2134 TM, Netherlands
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Leiden, 2333 ZA, Netherlands
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Utrecht, 3508 GA, Netherlands
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Gdansk, 80-214, Poland
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Nowa Sól, 67-106, Poland
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Skórzewo, 60-185, Poland
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Warsaw, 02-781, Poland
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Braga, 4710, Portugal
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Coimbra, 3000-075, Portugal
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Faro, 8000-386, Portugal
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Lisbon, 1169-050, Portugal
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Lisbon, 1350-352, Portugal
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Lisbon, 1500-458, Portugal
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Lisbon, 1500-650, Portugal
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Lisbon, 1649-035, Portugal
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Belgrade, 11000, Serbia
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Kamenitz, 21204, Serbia
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Busan, 47392, South Korea
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Goyang-si, 10408, South Korea
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Incheon, 405-760, South Korea
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Seongnam-si, 13620, South Korea
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Seoul, 02841, South Korea
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Seoul, 03080, South Korea
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Seoul, 06351, South Korea
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Seoul, 06591, South Korea
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Seoul, 07985, South Korea
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Barcelona, 08035, Spain
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Barcelona, 08036, Spain
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Barcelona, 08041, Spain
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Barcelona, 08208, Spain
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L'Hospitalet de Llobregat, 08907, Spain
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Las Palmas de Gran Canaria, 35016, Spain
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Madrid, 28033, Spain
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Madrid, 28040, Spain
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Madrid, 28046, Spain
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Pamplona, 31008, Spain
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Seville, 41009, Spain
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Taichung, 40447, Taiwan
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Taichung, 40705, Taiwan
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Tainan, 70403, Taiwan
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Tainan, 710, Taiwan
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Bangkok, 10330, Thailand
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Dusit, 10300, Thailand
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Songkhla, 90110, Thailand
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Adana, 01060, Turkey (Türkiye)
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Ankara, 06560, Turkey (Türkiye)
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Ankara, 06620, Turkey (Türkiye)
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Ankara, 5000, Turkey (Türkiye)
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Ankara, Turkey (Türkiye)
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Antalya, 07025, Turkey (Türkiye)
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Cordaleo, 35575, Turkey (Türkiye)
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Edirne, 22030, Turkey (Türkiye)
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Istanbul, 32098, Turkey (Türkiye)
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Istanbul, 34722, Turkey (Türkiye)
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London, EC1A 7BE, United Kingdom
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London, NW1 2PG, United Kingdom
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Hanoi, 100000, Vietnam
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Hà Nội, 100000, Vietnam
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Ho Chi Minh City, 700000, Vietnam
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Huế, 530000, Vietnam
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 17, 2021
First Posted
July 14, 2021
Study Start
August 5, 2021
Primary Completion
April 30, 2026
Study Completion (Estimated)
September 8, 2028
Last Updated
April 14, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- 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.
- 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
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.