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

NCT ID: NCT04960709

Last Updated: 2025-12-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

712 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-08-05

Study Completion Date

2028-09-08

Brief Summary

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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.

Detailed Description

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Not provided

Conditions

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Muscle Invasive Bladder Cancer

Keywords

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Bladder Cancer Immunotherapy PD-L1 Durvalumab (MEDI4736) Tremelimumab Enfortumab Vedotin (PADCEV)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Parallel
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Durvalumab + Tremelimumab + Enfortumab Vedotin

Participants 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.

Group Type EXPERIMENTAL

Durvalumab

Intervention Type DRUG

Anti- PD-L1 Antibody

Tremelimumab

Intervention Type DRUG

Human IgG2 mAb

Enfortumab Vedotin

Intervention Type DRUG

Nectin-4-directed antibody and microtubule inhibitor conjugate

Radical Cystectomy

Intervention Type PROCEDURE

For cisplatin-ineligible or cisplatin-refusal patients

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.

Group Type EXPERIMENTAL

Durvalumab

Intervention Type DRUG

Anti- PD-L1 Antibody

Enfortumab Vedotin

Intervention Type DRUG

Nectin-4-directed antibody and microtubule inhibitor conjugate

Radical Cystectomy

Intervention Type PROCEDURE

For cisplatin-ineligible or cisplatin-refusal patients

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.

Group Type ACTIVE_COMPARATOR

Radical Cystectomy

Intervention Type PROCEDURE

For cisplatin-ineligible or cisplatin-refusal patients

Interventions

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Durvalumab

Anti- PD-L1 Antibody

Intervention Type DRUG

Tremelimumab

Human IgG2 mAb

Intervention Type DRUG

Enfortumab Vedotin

Nectin-4-directed antibody and microtubule inhibitor conjugate

Intervention Type DRUG

Radical Cystectomy

For cisplatin-ineligible or cisplatin-refusal patients

Intervention Type PROCEDURE

Other Intervention Names

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IMFINZI MEDI4736 PADCEV

Eligibility Criteria

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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 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)

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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

130 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AstraZeneca

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Research Site

Orange, California, United States

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Santa Monica, California, United States

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New Haven, Connecticut, United States

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Washington D.C., District of Columbia, United States

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Fort Myers, Florida, United States

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Coeur d'Alene, Idaho, United States

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Maywood, Illinois, United States

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Indianapolis, Indiana, United States

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Iowa City, Iowa, United States

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Louisville, Kentucky, United States

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Scarborough, Maine, United States

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Boston, Massachusetts, United States

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Brighton, Michigan, United States

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Jackson, Mississippi, United States

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Las Vegas, Nevada, United States

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Saddle Brook, New Jersey, United States

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Brooklyn, New York, United States

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Buffalo, New York, United States

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New York, New York, United States

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Syracuse, New York, United States

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Portland, Oregon, United States

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Hershey, Pennsylvania, United States

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Pittsburgh, Pennsylvania, United States

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Knoxville, Tennessee, United States

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Austin, Texas, United States

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Dallas, Texas, United States

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Fort Worth, Texas, United States

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Houston, Texas, United States

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Irving, Texas, United States

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Norfolk, Virginia, United States

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Spokane, Washington, United States

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Buenos Aires, , Argentina

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CABA, , Argentina

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Ciudad de Buenos Aires, , Argentina

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Ciudad de Buenos Aires, , Argentina

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Pergamino, , Argentina

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Pilar, , Argentina

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Graz, , Austria

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Krems, , Austria

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Linz, , Austria

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Salzburg, , Austria

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Vienna, , Austria

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Vienna, , Austria

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Wiener Neustadt, , Austria

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Barretos, , Brazil

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Curitiba, , Brazil

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Fortaleza, , Brazil

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Porto Alegre, , Brazil

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Porto Alegre, , Brazil

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Porto Alegre, , Brazil

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Porto Alegre, , Brazil

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Rio de Janeiro, , Brazil

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Santa Maria, , Brazil

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Santo André, , Brazil

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São Paulo, , Brazil

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São Paulo, , Brazil

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Săo Paulo, , Brazil

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Uberlândia, , Brazil

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Abbotsford, British Columbia, Canada

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Toronto, Ontario, Canada

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Québec, Quebec, Canada

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Sherbrooke, Quebec, Canada

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Santiago, , Chile

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Santiago, , Chile

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Amiens, , France

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Bayonne, , France

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Clermont-Ferrand, , France

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Lille, , France

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Lyon, , France

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Marseille, , France

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Marseille, , France

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Montpellier, , France

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Nice, , France

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Pierre-Bénite, , France

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Quint-Fonsegrives, , France

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Saint-Priez En Jarez, , France

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Strasbourg, , France

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Suresnes, , France

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Vandœuvre-lès-Nancy, , France

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Bielefeld, , Germany

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Bochum, , Germany

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Cologne, , Germany

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Düsseldorf, , Germany

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Giessen, , Germany

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Hanover, , Germany

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Herne, , Germany

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Magdeburg, , Germany

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Mainz, , Germany

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Mannheim, , Germany

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München, , Germany

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Münster, , Germany

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Regensburg, , Germany

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Reutlingen, , Germany

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Ulm, , Germany

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Athens, , Greece

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Athens, , Greece

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Maroussi, Athens, , Greece

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Shatin, , Hong Kong

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Hadera, , Israel

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Haifa, , Israel

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Jerusalem, , Israel

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Jerusalem, , Israel

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Tel Aviv, , Israel

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Bari, , Italy

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Florence, , Italy

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Meldola, , Italy

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Milan, , Italy

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Milan, , Italy

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Padua, , Italy

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Pozzuoli, , Italy

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Reggio Emilia, , Italy

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Roma, , Italy

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Roma, , Italy

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Roma, , Italy

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Terni, , Italy

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Tricase, , Italy

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Verona, , Italy

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Bunkyō City, , Japan

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Fukuoka, , Japan

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Hamamatsu, , Japan

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Ichikawa-shi, , Japan

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Kanazawa, , Japan

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Kashihara-shi, , Japan

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Kawasaki-shi, , Japan

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Kita-gun, , Japan

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Kobe, , Japan

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Kumamoto, , Japan

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Matsuyama, , Japan

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Miyazaki, , Japan

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Niigata, , Japan

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Okayama, , Japan

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Osaka, , Japan

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Osaka, , Japan

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Osakasayama-shi, , Japan

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Toyama, , Japan

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Tsukuba, , Japan

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Yokohama, , Japan

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Colima, , Mexico

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Monterrey, , Mexico

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Arnhem, , Netherlands

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Breda, , Netherlands

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Groningen, , Netherlands

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Hoofddorp, , Netherlands

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Leiden, , Netherlands

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Utrecht, , Netherlands

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Gdansk, , Poland

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Nowa Sól, , Poland

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Skórzewo, , Poland

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Warsaw, , Poland

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Braga, , Portugal

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Coimbra, , Portugal

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Faro, , Portugal

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Lisbon, , Portugal

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Lisbon, , Portugal

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Lisbon, , Portugal

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Belgrade, , Serbia

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Kamenitz, , Serbia

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Busan, , South Korea

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Goyang-si, , South Korea

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Incheon, , South Korea

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Seongnam-si, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Barcelona, , Spain

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Barcelona, , Spain

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Barcelona, , Spain

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Barcelona, , Spain

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L'Hospitalet de Llobregat, , Spain

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Las Palmas de Gran Canaria, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Pamplona, , Spain

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Seville, , Spain

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Taichung, , Taiwan

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Taichung, , Taiwan

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Tainan, , Taiwan

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Tainan, , Taiwan

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Bangkok, , Thailand

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Dusit, , Thailand

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Songkhla, , Thailand

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Adana, , Turkey (Türkiye)

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Ankara, , Turkey (Türkiye)

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Ankara, , Turkey (Türkiye)

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Ankara, , Turkey (Türkiye)

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Ankara, , Turkey (Türkiye)

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Antalya, , Turkey (Türkiye)

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Edirne, , Turkey (Türkiye)

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Istanbul, , Turkey (Türkiye)

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Istanbul, , Turkey (Türkiye)

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Karşıyaka, , Turkey (Türkiye)

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London, , United Kingdom

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London, , United Kingdom

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Hanoi, , Vietnam

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Hà Nội, , Vietnam

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Ho Chi Minh City, , Vietnam

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Huế, , Vietnam

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Countries

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Colombia Russia Ukraine United States Argentina Austria Brazil Canada Chile France Germany Greece Hong Kong Israel Italy Japan Mexico Netherlands Poland Portugal Serbia South Korea Spain Taiwan Thailand Turkey (Türkiye) United Kingdom Vietnam

Other Identifiers

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2020-005452-38

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

D910PC00001

Identifier Type: -

Identifier Source: org_study_id