Active — Not RecruitingPhase 3

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

United States712 participantsStarted 2021-08-05

Plain-language 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.

Who can participate

Age range18 Years – 130 Years

SexALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

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.

What they're measuring

To assess the safety and tolerability as evaluated by adverse events occurring throughout the study (Safety Run-In part)

Timeframe: 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)

Timeframe: 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)

Timeframe: 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)

Timeframe: 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)

Timeframe: 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)

Trial details

NCT IDNCT04960709

SponsorAstraZeneca

Sponsor typeINDUSTRY

Study typeINTERVENTIONAL

Primary completion2026-04-30

View on ClinicalTrials.gov More Muscle Invasive Bladder Cancer trials

Plain-language summary

Who can participate

Age range18 Years – 130 Years

SexALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

What they're measuring

To assess the safety and tolerability as evaluated by adverse events occurring throughout the study (Safety Run-In part)

Timeframe: At completion of study treatment by the last patient and at 3 months.

Timeframe: Up to 84 months