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

• Register: ClinicalTrials.gov
• Last refreshed on: 28 August 2023
• Main ID: NCT03406650
• Date of registration: 22/12/2017
• Prospective Registration: Yes
• Primary sponsor: Swiss Group for Clinical Cancer Research
• Public title: Neoadjuvant and Adjuvant Durvalumab in Combination With Neoadjuvant Chemotherapy in Patients With Operable Urothelial Cancer. SAKK 06/17
• Scientific title: Neoadjuvant and Adjuvant Durvalumab in Combination With Neoadjuvant Chemotherapy in Patients With Operable Urothelial Cancer. A Multicenter, Single-arm Phase II Trial
• Date of first enrolment: May 15, 2018
• Target sample size: 61
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT03406650
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

Germany, Switzerland

Contacts

• Name: Richard Cathomas, MD
• Affiliation: Kantonsspital Graubünden, Chur

Key inclusion & exclusion criteria

Inclusion Criteria:

- 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)

- Women with child-bearing potential are using effective contraception (for details of
definition see 9.9), are not pregnant or lactating and agree not to become pregnant
during trial treatment and during 90 days thereafter. A negative pregnancy test before
inclusion into the trial is required for all women with child-bearing potential

- Men agree not to father a child during trial treatment and during 90 days thereafter

- Body weight > 30kg.

Exclusion Criteria:

- 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

- Patients with celiac disease controlled by diet alone

- Known history of human immunodeficiency virus (HIV) or active chronic Hepatitis C or
Hepatitis B Virus infection or any uncontrolled active systemic infection requiring
intravenous (iv) antimicrobial treatment

- History of allogeneic organ transplant

- Receipt of live attenuated vaccine within 30 days prior to registration. Note:
Patients, if enrolled, should not receive live vaccine during trial treatment and up
to 30 days after the last dose

- Uncontrolled intercurrent illness, including but not limited to, ongoing or active
infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable
angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic
gastrointestinal conditions associated with diarrhea, or psychiatric illness/social
situations that would limit compliance with study requirement, substantially increase
risk of incurring AEs or compromise the ability of the patient to give written
informed consent

- Any concurrent drug contraindicated for blocking the effect of durvalumab; this
includes systemic corticosteroids, methotrexate, azathioprine, and tumor necrosis
factor (TNF)-a blockers. Any concurrent drug contraindicated for use with the other
trial drugs according to the locally approved product information

- Known hypersensitivity to cisplatin, gemcitabine or durvalumab or to any excipient

- Female patients who are pregnant or breastfeeding or male or female patients of
reproductive potential who are not willing to employ effective birth control from
screening to 90 days after the last dose of durvalumab.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Urothelial Cancer

Intervention(s)

Drug: Neoadjuvant and adjuvant durvalumab

Primary Outcome(s)

event-free survival (EFS) [Time Frame: 2 years after treatment start]

Secondary Outcome(s)

Quality of resection [Time Frame: after surgery or the latest 20 weeks after registration]

Event-free survival (EFS) [Time Frame: at the occurrence of the event or latest 5 years after surgery]

Adverse events [Time Frame: within treatment start and 90 days after last trial treatment and resolution of all related AEs thereafter (at the latest 5 years after surgery)]

Overall survival (OS) [Time Frame: at death or latest 5 years after surgery]

Pathological complete response rate (ypT0) [Time Frame: after surgery or the latest 20 weeks after registration]

Pattern of recurrence [Time Frame: after recurrence or latest 5 years after surgery]

Recurrence-free survival (RFS) after R0 resection [Time Frame: at recurrence or latest 5 years after surgery]

Treatment feasibility [Time Frame: after treatment end or the latest 73 weeks after registration]

Pathological response rate (PaR) defined by pathological downstaging to =ypT1N0M0 [Time Frame: after surgery or the latest 20 weeks after registration]

Secondary ID(s)

SAKK 06/17

2017-003565-10

Source(s) of Monetary Support

Please refer to primary and secondary sponsors