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NCT03603184 | SNCTP000003119

Atezolizumab in Kombination mit Paclitaxel and Carboplatin für Patientinnen mit fortgeschrittenem/wiederkehrendem Gebärmutterkrebs – eine Phase III doppel-blinde randomisierte Placebo kontrollierte Studie.

Data source: BASEC (Imported from 24.05.2020), WHO (Imported from 22.03.2020)
Changed: 22.05.2020
Disease category: Gebärmutterkrebs

Brief description of trial (Source of data: BASEC)

Diese Studie wird untersuchen, ob die Gabe von Atezolizumab zusammen mit der Standard Chemotherapie (Carboplatin/Paclitaxel) wirksam und sicher ist. Voraussichtlich werden 550 Patientinnen an dieser internationalen Studie teilnehmen. Sie werden nach dem Zufallsprinzip in 2 Behandlungsgruppen eingeteilt: Chemotherapie+ Atezolizumab oder Chemotherapie + Placebo. Atezolizumab ist ein Antikörper (ein Protein, das vom Immunsystem des Körpers hergestellt wird), der auf das Immunsystem einwirkt. Atezolizumab ist ein neuer, experimenteller Wirkstoff, der bei Menschen mit unterschiedlichen Tumorerkrankungen verabreicht wird und ist von den Gesundheitsbehörden in der Schweiz zur Behandlung des lokal fortgeschrittenen oder metastasierten nicht-kleinzelligen Lungenkarzinoms nach vorausgegangener Chemotherapie zugelassen, aber noch nicht zur Behandlung von Gebärmutterkrebs.

Health conditions investigated (Source of data: BASEC)

Fortgeschrittener wiederkehrender Gebärmutterkrebs

Health conditions (Source of data: WHO)

Endometrial Cancer

Rare disease (Source of data: BASEC)

No

Intervention investigated (e.g. drug, therapy or campaign) (Source of data: BASEC)

Arm A: Die Chemotherapie + Placebo wird alle 3 Wochen verabreicht und maximal werden 8 Verabreichungen erfolgen.

Arm B: Die Chemotherapie + Atezolizumab wird alle 3 Wochen verabreicht und maximal werden 8 Verabreichungen erfolgen.

Anschliessend wird das Placebo (Arm A) oder Atezolizumab (Arm B) alleine alle 3 Wochen verabreicht, solange die Krankheit nicht fortschreitet (Erhaltungstherapie).

Während der Chemotherapie wird alle 9 Wochen die Wirkung auf den Tumor mittels radiologischen Kontrolle geprüft. Während der Erhaltungstherapie erfolgen die Kontrolle alle 12 Wochen und danach alle 6 Monate.

Interventions (Source of data: WHO)

Drug: Atezolizumab;Drug: Placebos;Drug: Paclitaxel;Drug: Carboplatin

Criteria for participation in trial (Source of data: BASEC)

II-1. Patientinnen mit kürzlich diagnostiziertem, histologisch bestätigtem, Stadium III-IV Gebärmutterhalskrebs/Endometeriumkarzinom/karzinosarkom, bei welchen nach einer Operation eine mess- oder auswertbarer Resterkrankung festgestellt wurde oder bei welchen die Krebserkrankung inoperabel ist und welche nicht auf eine erste systematische Krebstherapie ansprechen. Zur Diagnosesicherung wird eine Biopsie benötigt. Patientinnen mit wiederkehrendem Endometriumkarzinom/Gebärmutterhalskrebs falls sie für den rückfälligen Krebs noch nicht behandelt wurden.
I-2. Allgemeinszustand nach der Eastern Cooperative Oncology Group (ECOG) 0-2.
I-3. Alter ≥ 18 Jahre

Exclusion criteria (Source of data: BASEC)

E-1. Andere maligne Erkrankungen in den letzten 5 Jahren ausser: angemessen behandelter nicht-Melanoma Hautkrebs, kurativ behandelter In-Situ-Krebs des Gebärmutterhalses, Duktalkarzinom in situ (DCIS) der Brust. Patientinnen mit einer Vorgeschichte von lokalisierten malignen Erkrankungen, die vor mehr als 5 Jahren diagnostiziert wurden, können in Frage kommen, sofern die Patientinnen die adjuvante systemische Therapie vor der Randomisierung abgeschlossen haben und die Patientinnen frei von rezidivierenden oder metastasierenden Erkrankungen bleiben.
E-2 Patientinnen mit Leiomyosarkom des Uterus
E-3 Grössere Operationen innerhalb von 4 Wochen vor Behandlungsbeginn oder Patientinnen, welche sich nicht vollständig von den Auswirkungen einer grösseren Operation erholt haben.

Inclusion/Exclusion Criteria (Source of data: WHO)


Inclusion Criteria:

I-1. Newly diagnosed, histologically-confirmed with residual disease after surgery either
measurable or evaluable, or inoperable stage III-IV endometrial carcinoma/carcinosarcoma,
after diagnostic biopsy, and naïve to first line systemic anti-cancer treatment. Recurrent
endometrial cancer patients if not yet treated for recurrent disease.

I-2. Eastern Cooperative Oncology Group (ECOG) performance status 0-2 I-3. Age = 18 years
I-4. Only one prior line of systemic platinum-based regimen is permitted if the
platinum-free interval = 6 months. Such prior line is the up-front/adjuvant treatment which
can be concurrent chemoradiation or concurrent chemoradiation followed by chemotherapy or
only chemotherapy.

I-5. Patients with history of primary breast cancer may be eligible provided they completed
their definitive anticancer treatment more than 3 years ago and they remain breast cancer
disease free prior to start of study treatment.

I-6. Previous pelvic and outside pelvis radiation is allowed if completed more than 6 weeks
ago.

I-7. Signed informed consent and ability to comply with treatment and follow-up.

I-8. Representative FFPE tumor sample or, only if unfeasible, at least 20 unstained slides
from initial surgery or from diagnostic biopsy, in case surgery was not performed,
available and sent to central laboratory for Micro Satellite (MS) determination prior to
randomization.

I-9. Patients must have normal organ and bone marrow function :

1. Haemoglobin = 10.0 g/dL.

2. Absolute neutrophil count (ANC) = 1.5 x 109/L.

3. Platelet count = 100 x 109/L.

4. Total bilirubin = 1.5 x institutional upper limit of normal (ULN).

5. Aspartate aminotransferase /Serum Glutamic Oxaloacetic Transaminase (ASAT/SGOT)) and
Alanine aminotransferase /Serum Glutamic Pyruvate Transaminase (ALAT/SGPT)) = 2.5 x
ULN, unless liver metastases are present in which case they must be = 5 x ULN.

6. Serum creatinine = 1.5 x institutional ULN

Exclusion Criteria:

E-1. Other malignancy within the last 5 years except: adequately treated non-melanoma skin
cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS) of
the breast. Patients with a history of localized malignancy diagnosed over 5 years ago may
be eligible provided they completed their adjuvant systemic therapy prior to randomization
and that the patient remains free of recurrent or metastatic disease.

E-2. Patients with uterine leiomyosarcoma . E-3. Major surgery within 4 weeks of starting
study treatment or patients who have not completely recovered from the effects of any major
surgery.

E-4. Previous allogeneic bone marrow transplant or previous solid organ transplantation.

E-5. Administration of other simultaneous chemotherapy drugs, any other anticancer therapy
or anti-neoplastic hormonal therapy, or simultaneous radiotherapy during the trial
treatment period (hormonal replacement therapy is permitted).

E-6. Prior treatment with CD137 agonists or immune checkpoint blockade therapies, anti-PD1,
or anti-PDL1 therapeutic antibodies or anti-CTLA4 .

E-7. Treatment with systemic immunostimulatory agents (including but not limited to
interferon-alpha (IFN-a) and interleukin-2 (IL-2) within 4 weeks or five half-lives of the
drug (whichever is shorter) prior to Cycle 1, Day 1.

E-8. Treatment with systemic corticosteroids or other systemic immunosuppressive
medications (including but not limited to prednisone, dexamethasone, cyclophosphamide,
azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [TNF] agents)
within 2 weeks prior to Cycle 1, Day 1, or anticipated requirement for systemic
immunosuppressive medications during the trial. However, please note that the use of
inhaled corticosteroids for chronic obstructive pulmonary disease or for asthma is allowed,
as well as the use of mineralocorticoids (e.g., fludrocortisones) and low-dose supplemental
corticosteroids for adrenocortical insufficiency and for patients with orthostatic
hypotension. The use of corticosteroids as premedication for paclitaxel-based regimen is
allowed).

E-9. History of autoimmune disease, including but not limited to myasthenia gravis,
myositis,autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis,
inflammatory bowel disease, vascular thrombosis associated with anti-phospholipid syndrome,
Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis,
vasculitis, or glomerulonephritis [please note: patients with a history of autoimmune
hypothyroidism on a stable dose of thyroid replacement hormone are eligible; patients with
controlled Type 1 diabetes mellitus on a stable insulin regimen are eligible; history of
idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing
pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia) is permitted].

E-10. Immunocompromised patients, e.g., patients who are known to be serologically positive
for human immunodeficiency virus (HIV).

E-11. Patients with active hepatitis B (defined as having a positive hepatitis B surface
antigen [HBsAg] test at screening) or hepatitis C .

1. Patients with past hepatitis B virus (HBV) infection or resolved HBV infection
(defined as having a negative HBsAg test and a positive total hepatitis B core
antibody [HBcAb]) are eligible only if hepatitis B virus (HBV) DNA is negative. The
HBV DNA test will be performed only for patients who have a positive total HBcAb test.

2. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase
chain reaction (PCR) is negative for HCV RNA. The HCV RNA test will be performed only
for patients who have a positive HCV antibody test.

E-12. Active tuberculosis (all patients will have tuberculin [PPD] skin test or
Interferon-Gamma Releasing Assay [IGRA] done locally prior to inclusion to study) E-13.
Signs or symptoms of infection within 2 weeks prior to Cycle 1, Day 1 E-14. Administration
of a live, attenuated vaccine within 4 weeks prior to Cycle 1, Day 1 or anticipation that
such a live attenuated vaccine will be required during the study. Influenza vaccination
should be given during influenza season only (example approximately October to March in the
Northern Hemisphere). Patients must not receive live, attenuated influenza vaccine.

E-15. Clinically significant (e.g. active) cardiovascular disease, including:

1. Myocardial infarction or unstable angina within = 6 months of randomization,

2. New York Heart Association (NYHA) = grade 2 congestive heart failure (CHF),

3. Poorly controlled cardiac arrhythmia despite medication (patients with rate controlled
atrial fibrillation are eligible),

Further information on the trial in WHO primary registry

https://clinicaltrials.gov/show/NCT03603184

Further information on the trial from WHO database (ICTRP)

http://apps.who.int/trialsearch/Trial2.aspx?TrialID=NCT03603184

Further information on trial

Date trial registered

21.05.2018

Incorporation of the first participant

02.10.2018

Recruitment status

Recruiting

Academic title (Source of data: WHO)

Phase III Double-blind Randomized Placebo Controlled Trial of Atezolizumab in Combination With Paclitaxel and Carboplatin in Women With Advanced/Recurrent Endometrial Cancer

Type of trial (Source of data: WHO)

Interventional

Design of the trial (Source of data: WHO)

Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).

Phase (Source of data: WHO)

Phase 3

Primary end point (Source of data: WHO)

OS;PFS

Secundary end point (Source of data: WHO)

Objective response rate;Compliance: Dose intensity;Compliance: Reasons for discontinuation and treatment modification;Compliance: Number of administered cycles;Quality of life: GP5 item;Quality of life: QLQ-EN24 questionnaire;Quality of life: EORTC QLQ-C30 questionnaire;Safety: Number of patients with at least a SUSAR;Safety: Number of patients with at least a SADR;Safety: Number of patients with at least a SAE;Safety: Type, frequency and nature of SAEs;Safety: Number of patients experiencing grade 3-4 toxicity for each toxicity;Safety: Maximum toxicity grade;Duration of response

Contact information (Source of data: WHO)

Please refer to primary and secondary sponsors

Trial sites

Trial sites in Switzerland (Source of data: BASEC)

Baden, Basel, Bellinzona, Bern, Frauenfeld, Luzern, Winterthur, Zürich

Countries (Source of data: WHO)

Austria, Germany, Italy, Japan, Spain, Switzerland, United Kingdom

Contact for further information on the trial

Details of contact in Switzerland (Source of data: BASEC)

SAKK, Jessica Schulz
+41 31 389 91 91
trials@sakk.ch

Contact for general information (Source of data: WHO)

Nicoletta Colombo, MD;Elena Biagioli
Istituto Europeo di Oncologia (IEO) - Milan
+390239014650
attend@marionegri.it

Contact for scientific information (Source of data: WHO)

Nicoletta Colombo, MD;Elena Biagioli
Istituto Europeo di Oncologia (IEO) - Milan
+390239014650
attend@marionegri.it

Principal Sponsor/Investigator

Principal sponsor (Source of data: WHO)

Mario Negri Institute for Pharmacological Research

Further trial identification numbers

BASEC ID (Source of data: BASEC)

2018-01772

Secondary ID (Source of data: WHO)

IRFMN-EN-7556