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Brief Title: Treatment Combination of Durvalumab, Tremelimumab and Enfortumab Vedotin or Durvalumab and Enfortumab Vedotin in Patients With Muscle Invasive Bladder Cancer Ineligible to Cisplatin

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)

INTRODUCTION

  • Org Study ID: D910PC00001
  • Secondary ID: N/A
  • NTC ID: NCT04960709
  • Sponsor: AstraZeneca

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 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.

DETAILED DESCRIPTION

Not provided

  • Overall Status
    Recruiting
  • Start Date
    August 5, 2021
  • Phase
    Phase 3
  • Study Type
    Interventional

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Compare efficacy of durvalumab + tremelimumab + EV relative to cystectomy alone on pCR rate (Safety Run-In and Main Study)

Primary Outcome 1 - Timeframe: Up to 3 years

Primary Outcome 2 - Measure: Compare efficacy of durvalumab + tremelimumab + EV relative to cystectomy alone on EFS (Safety Run-In and Main Study)

Primary Outcome 2 - Timeframe: Up to 3 years

Primary Outcome 3 - Measure: Safety and Tolerability as evaluated by adverse events occurring throughout the study (Safety Run-In part)

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

Primary Outcome 4 - Measure: 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)

Primary Outcome 4 - Timeframe: Up to 84 months

Primary Outcome 5 - Measure: 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)

Primary Outcome 5 - Timeframe: Up to 84 months

Primary Outcome 6 - Measure: 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)

Primary Outcome 6 - Timeframe: Up to 84 months

Primary Outcome 7 - Measure: 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)

Primary Outcome 7 - Timeframe: Up to 84 months

Primary Outcome 8 - Measure: 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)

Primary Outcome 8 - Timeframe: Up to 84 months

Primary Outcome 9 - Measure: 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)

Primary Outcome 9 - Timeframe: Up to 84 months

Primary Outcome 10 - Measure: 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)

Primary Outcome 10 - Timeframe: Up to 84 months

Primary Outcome 11 - Measure: 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)

Primary Outcome 11 - Timeframe: Up to 84 months

Primary Outcome 12 - Measure: 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)

Primary Outcome 12 - Timeframe: Up to 84 months

Primary Outcome 13 - Measure: Changes in WHO/ECOG performance status (Safety Run-In part)

Primary Outcome 13 - Timeframe: Up to 84 months

CONDITION

  • Muscle Invasive Bladder Cancer

ELIGIBILITY

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.

Gender: All

Minimum Age: 18 Years

Maximum Age: 130 Years

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: N/A

Role: N/A

Affiliation: N/A

Overall Contact

Name: N/A

Phone: 1-877-240-9479

Email: information.center@astrazeneca.com

LOCATION

Facility Status Contact