Neoadjuvant and Adjuvant Durvalumab in Combination With Neoadjuvant Chemotherapy in Patients With Operable Urothelial Cancer.

NCT03406650 | Completed Phase 2 DMC

• 2 other identifiers: SAKK 06/172017-003565-10
• Study Type: interventional
• Target: 61
• Locations: 2 countries
• Sites: 17

Brief Summary

The main objective is to demonstrate that the addition of neoadjuvant and adjuvant immunotherapy with durvalumab, to standard neoadjuvant chemotherapy (with cisplatin/gemcitabine) and surgery in urothelial carcinoma could improve event-free survival.

Conditions

Urothelial Cancer

Keywords

muscle invasive urothelial cancer; cancer; immunotherapy; durvalumab; MEDI4736; adjuvant; neoadjuvant; radical cystectomy; bladder

Outcome Measures

Primary Outcomes (1)

• event-free survival (EFS)

  The primary endpoint of the trial is Event-free survival (EFS) at 2 years after neoadjuvant trial treatment start. Event-free survival is defined as the time from treatment start until one of the following events, whichever comes first: * Progression during neoadjuvant treatment leading to inoperability * Recurrence of locoregional disease after surgery * Appearance of metastases at any localization * Death Patients not experiencing an event will be censored at the date of the last available assessment before initiation of a subsequent treatment, if any.

  2 years after treatment start

Secondary Outcomes (9)

• Event-free survival (EFS)

  at the occurrence of the event or latest 5 years after surgery

• Recurrence-free survival (RFS) after R0 resection

  at recurrence or latest 5 years after surgery

• Overall survival (OS)

  at death or latest 5 years after surgery

• Quality of resection

  after surgery or the latest 20 weeks after registration

• Pathological complete response rate (ypT0)

  after surgery or the latest 20 weeks after registration

Study Arms (1)

Durvalumab in combination with standard therapy

EXPERIMENTAL

Combination of standard therapy consisting (4 cycles cisplatin/ gemcitabin followed by surgery) with 4 cycles of neoadjuvant durvalumab and 10 cycles of adjuvant durvalumab

Drug: Neoadjuvant and adjuvant durvalumab

Interventions

Neoadjuvant and adjuvant durvalumab DRUG

Neoadjuvant durvalumab 1500 mg q3w for 4 cycles Adjuvant durvalumab 1500 mg q4w for 10 cycles

Also known as: MEDI4736

Durvalumab in combination with standard therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent according to ICH/GCP regulations before registration and prior to any trial specific procedures
• Histologically proven urothelial cell carcinoma of the bladder, urethra or upper urinary tract (T2, T3, or T4a and ≤ N1 (defined as a solitary lymph node ≤ 2 cm in the greatest dimension), M0) and be considered suitable for curative multimodality treatment including surgery by a multidisciplinary tumor board. Cytological diagnosis is only allowed for upper tract urothelial carcinoma. In these cases tumor has to be documented by urography
• All histological subtypes eligible if urothelial carcinoma predominant (exception: small cell component)
• Age ≥ 18 years
• WHO performance status 0-1
• Bone marrow function: hemoglobin ≥ 90 g/L, neutrophil count ≥ 1.5 x 109/L, platelet count ≥ 100 x 109/L
• Hepatic function: bilirubin ≤ 1.5 x ULN (except for patients with Gilbert's disease ≤ 3.0 x ULN), AST ≤ 2.5 x ULN and ALT ≤ 2.5 x ULN, alkaline phosphatase ≤ 2.5 x ULN
• Renal function: estimated glomerular filtration rate (eGFR) \> 50 mL/min/1.73m², according to CKD-EPI formula
• Cardiac function: Left ventricular Ejection Fraction (LVEF) ≥ 50% as determined by echocardiography (ECHO)
• Men agree not to father a child during trial treatment and during 90 days thereafter
• Body weight \> 30kg.

You may not qualify if:

• Any pathological evidence of small-cell carcinoma component
• Presence of any distant metastasis
• History of hematologic or primary solid tumor malignancy, unless in remission for at least 3 years before registration, with the exception of adequately treated cervical carcinoma in situ, localized non-melanoma skin cancer or low risk localized prostate cancer (T1-T2a, Gleason \<7, PSA \<10ng/ml)
• Any previous treatment with a PD-1 or PD-L1 inhibitor, including durvalumab
• Concurrent treatment with prednisone (or equivalent); except for the prophylactic medication before chemotherapy, treatment of acute hypersensitivity reactions or chronic treatment (initiated \> 6 months prior to registration) at low dose (≤ 10 mg/day of prednisone or an equivalent corticosteroid)
• Concurrent treatment with other experimental drugs or other anticancer therapy, treatment in a clinical trial within 28 days prior to registration
• Current or prior use of immunosuppressive medication within 28 days prior to registration, with the exception of intranasal and inhaled corticosteroids or systemic corticosteroids
• Major surgical procedure within 28 days prior to registration
• Preexisting peripheral neuropathy (\> grade 1)
• Uncontrolled diabetes mellitus
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc\]). The following are exceptions to this criterion:
• Patients with vitiligo or alopecia
• Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
• Any chronic skin condition that does not require systemic therapy
• Patients without active disease in the last 5 years may be included but only after consultation with the coordinating investigator

Sponsors & Collaborators

• Swiss Cancer Institute: lead

Study Sites (17)

Universitätsklinikum Düsseldorf

Düsseldorf, 40225, Germany

Location

Urologische Universitätsklinik Essen

Essen, 45147, Germany

Location

Kantonspital Aarau

Aarau, CH-5001, Switzerland

Location

Kantonsspital Baden

Baden, CH-5404, Switzerland

Location

Universitaetsspital Basel

Basel, 4031, Switzerland

Location

Inselspital

Bern, 3010, Switzerland

Location

Kantonsspital Graubünden

Chur, 7000, Switzerland

Location

Spital Thurgau AG

Frauenfeld, CH-8500, Switzerland

Location

Hopital Cantonal Universitaire de Geneve

Geneva, CH-1211, Switzerland

Location

Centre Hospitalier Universitaire Vaudois CHUV

Lausanne, CH-1011, Switzerland

Location

Luzerner Kantonsspital

Lucerne, 6000, Switzerland

Location

Kantonsspital St. Gallen

Sankt Gallen, CH-9007, Switzerland

Location

Kantonsspital Winterthur

Winterthur, 8401, Switzerland

Location

Klinik Hirslanden - Onkozentrum Hirslanden

Zurich, 8032, Switzerland

Location

OnkoZentrum Zürich

Zurich, 8038, Switzerland

Location

City Hospital Triemli

Zurich, 8063, Switzerland

Location

UniversitaetsSpital Zuerich

Zurich, 8091, Switzerland

Location

MeSH Terms

Conditions

Neoplasms

Interventions

Neoadjuvant Therapy; durvalumab

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics

Study Officials

• Richard Cathomas, MD

  Kantonsspital Graubünden, Chur

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 22, 2017
• First Posted: January 23, 2018
• Study Start: May 15, 2018
• Primary Completion: February 25, 2022
• Study Completion: January 31, 2025
• Last Updated: May 4, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

CH (15); DE (2)