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SNCTP000002860 | NCT03406650 | BASEC2018-00176

Studie SAKK 06/17 -
Durvalumab in Kombination mit Standard Chemotherapie bei Patienten mit einem operablen Karzinom des Harntrakts. Eine multizentrische einarmige Phase II Studie.

Data source: BASEC (Imported from 07.08.2020), WHO (Imported from 02.08.2020)
Changed: 16.06.2020
Disease category: Bladder Cancer, Surgery

Brief description of trial (Data source: BASEC)

Die Studie untersucht die Kombination der Standardtherapie mit Durvalumab. Das Ziel der Studie ist es, die Prognose von betroffenen Patienten zu verbessern und die Wirkung und Verträglichkeit des Antikörpers Durvalumab in dieser Situation zu untersuchen.
Diese Studie wird an mehreren Spitälern in der Schweiz und in Deutschland durchgeführt. Es werden 61 Patienten in die Studie eingeschlossen. Alle Studienteilnehmer werden die gleiche Behandlung erhalten. Diese besteht aus der Standardtherapie (Chemotherapie vor der Operation und anschliessend Operation) und der zusätzlichen Gabe des Studienmedikamentes Durvalumab (eine Immmuntherapie). Die Dauer der Behandlung beträgt 3 Monate vor der Operation und 9 Monate danach. Durvalumab ist ein Eiweiss, welches zu einer Aktivierung des körpereigenen Immunsystems führt („Immuntherapie“). Durvalumab ist als Medikament in der Schweiz noch nicht zugelassen.

Health conditions investigated (Data source: BASEC)

operablen Karzinom des Harntrakts

Health conditions (Data source: WHO)

Urothelial Cancer

Rare disease (Data source: BASEC)

Yes

Intervention investigated (e.g. drug, therapy or campaign) (Data source: BASEC)

Um an der Behandlung im Rahmen der Studie teilnehmen zu können, müssen Sie als Patient gewisse Einschlusskriterien erfüllen. Diese werden zunächst abgeklärt. Sollten Sie die Einschlusskriterien erfüllen und sich für die Studienteilnahme entscheiden, werden Sie zusätzlich zur Standardbehandlung das Studienmedikament, den anti-PD-L1 Antikörper (Durvalumab) erhalten. Die Standardbehandlung besteht aus 4 Zyklen einer Chemotherapie mit Cisplatin und Gemcitabin vor der Operation (sogenannt „neoadjuvant“) gefolgt von einer Operation des Tumors. Das Studienmedikament wird mit der Chemotherapie vor der Operation insgesamt vier Mal während 13 Wochen und nach der Operation (sogenannt „adjuvant“) alleine insgesamt 10 Mal während 40 Wochen verabreicht.
Im Rahmen der Studie sind regelmässige klinische Kontrollen und Blutuntersuchungen vor und nach der Operation vorgesehen. Eine radiologische Kontrolle mittels Computertomographie wird auch regelmässig durchgeführt; dabei wird die Wirksamkeit der Behandlung überprüft.

Interventions (Data source: WHO)

Drug: Neoadjuvant and adjuvant durvalumab

Criteria for participation in trial (Data source: BASEC)

Es können alle Personen teilnehmen, die an einem operablen Karzinom des Harntrakts (Blase oder Harnwege) leiden, mindestens 18 Jahre alt sind und einen Tumor haben, der chirurgisch entfernbar ist. Die Niere und die Leber müssen zudem ausreichend gut funktionieren.

Exclusion criteria (Data source: BASEC)

Nicht teilnehmen hingegen dürfen Personen, die Autoimmunerkrankungen oder chronische Infektionen haben und eine Dauertherapie mit Kortison (Steroide) benötigen. Patienten, die aufgrund von Zusatzerkrankungen nicht operiert werden können oder sich nicht einer Cisplatin-basierten Chemotherapie unterziehen können, müssen ebenfalls von dieser Studie ausgeschlossen werden.

Inclusion/Exclusion Criteria (Data source: WHO)


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.

Further information on the trial in WHO primary registry

https://clinicaltrials.gov/show/NCT03406650

Further information on the trial from WHO database (ICTRP)

http://apps.who.int/trialsearch/Trial2.aspx?TrialID=NCT03406650

Further information on trial

Date trial registered

22.12.2017

Incorporation of the first participant

15.05.2018

Recruitment status

Active, not recruiting

Academic title (Data source: WHO)

Neoadjuvant and Adjuvant Durvalumab in Combination With Neoadjuvant Chemotherapy in Patients With Operable Urothelial Cancer. A Multicenter, Single-arm Phase II Trial

Type of trial (Data source: WHO)

Interventional

Design of the trial (Data source: WHO)

Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).

Phase (Data source: WHO)

Phase 2

Primary end point (Data source: WHO)

event-free survival (EFS)

Secundary end point (Data source: WHO)

Event-free survival (EFS);Recurrence-free survival (RFS) after R0 resection;Overall survival (OS);Quality of resection;Pathological complete response rate (ypT0);Pathological response rate (PaR) defined by pathological downstaging to =ypT1N0M0;Pattern of recurrence;Treatment feasibility;Adverse events

Contact information (Data source: WHO)

Please refer to primary and secondary sponsors

Trial results (Data source: WHO)

Results summary

no information available yet

Link to the results in the primary register

no information available yet

Information on the availability of individual participant data

no information available yet

Trial sites

Trial sites in Switzerland (Data source: BASEC)

Aarau, Baden/Brugg, Basel, Bern, Chur, Geneva, Lausanne, St. Gallen, Winterthur

Countries (Data source: WHO)

Germany, Switzerland

Contact for further information on the trial

Details of contact in Switzerland (Data source: BASEC)

Martina Schneider
+41 31 389 91 91
trials@sakk.ch

Contact for general information (Data source: WHO)

Richard Cathomas, MD
Kantonsspital Graubünden, Chur

Contact for scientific information (Data source: WHO)

Richard Cathomas, MD
Kantonsspital Graubünden, Chur

Principal Sponsor/Investigator

Principal sponsor (Data source: WHO)

Swiss Group for Clinical Cancer Research

Authorisation by the ethics committee (Data source: BASEC)

Name of the authorising ethics committee (for multicentre studies only the lead committee)

Kantonale Ethikkommission Zürich

Date of authorisation by the ethics committee

08.05.2018

Further trial identification numbers

Trial identification number of the ethics committee (BASEC-ID) (Data source: BASEC)

2018-00176

Secondary ID (Data source: WHO)

2017-003565-10
SAKK 06/17