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SNCTP000003663 | NCT04177108 | BASEC2019-01946

Eine doppelblinde, placebokontrollierte, randomisierte Phase-III-Studie zu Ipatasertib in Kombination mit Atezolizumab und Paclitaxel als Behandlung von Patienten mit lokal fortgeschrittenem inoperablem oder metastasiertem dreifach negativem Brustkrebs

Data source: BASEC (Imported from 22.09.2021), WHO (Imported from 18.04.2021)
Changed: 15.09.2021
Disease category: Breast Cancer

Brief description of trial (Data source: BASEC)

Diese Studie wird weltweit mit ca. 1150 Patientinnen und Patienten durchgeführt und untersucht die Wirksamkeit von Ipatasertib in Kombination mit Atezolizumab und Paclitaxel gegen metastasierten TNBC. Die Behandlungskohorte wird anhand desTumors zugeteilt: es wird zwischen PD L1 positiven und PD L1 nicht-positiven Tumoren unterschieden. Innerhalb der Kohorten wird dann per Zufall über die Behandlungsgruppe (Behandlungsarm) entschieden. Die gesamte Studie dauert ca. 6 Jahre.

Health conditions investigated (Data source: BASEC)

Dreifach negativer Brustkrebs (triple-negative breast cancer (TNBC))

Health conditions (Data source: WHO)

Triple-Negative Breast Cancer

Rare disease (Data source: BASEC)

No

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

PD L1 nicht-positiver Tumor (Kohorte 1):
Experimenteller Arm (Arm A): Paclitaxel + Ipatasertib + Atezolizumab
Experimenteller Arm (Arm B): Paclitaxel + Ipatasertib + Placebo (für Atezolizumab)
Kontrollarm (Arm C): Paclitaxel + Placebo (für Ipatasertib) + Placebo (für Atezolizumab)

PD L1 positiver Tumor (Kohorte 2):
Experimenteller Arm (Arm A): Paclitaxel + Ipatasertib + Atezolizumab
Kontrollarm (Arm B): Paclitaxel + Placebo (für Ipatasertib) + Atezolizumab

Interventions (Data source: WHO)

Drug: Atezolizumab;Drug: Ipatasertib;Drug: Paclitaxel;Drug: Placebo for Atezolizumab;Drug: Placebo for Ipatasertib

Criteria for participation in trial (Data source: BASEC)

Frauen oder Männer mit lokal fortgeschrittenem, inoperablem oder metastasierendem, dreifach-negativem Adenokarzinom der Brust, die in diesem Setting keine vorherige systemische Chemotherapie erhalten haben, können für diese Studie in Frage kommen. Bei Patienten mit BRCA-assoziiertem Tumor sollte eine platinhaltige Chemotherapie als potenziell bevorzugte Behandlungsoption in Betracht gezogen werden, um festzustellen, ob diese Studie für diese Patienten geeignet sein könnte. Die Patienten können eine vorherige Chemotherapie im neoadjuvanten oder adjuvanten Setting erhalten haben, wenn die Behandlung mindestens 12 Monate vor der Randomisierung abgeschlossen wurde. Die lokal fortgeschrittene, inoperable Erkrankung darf nicht mit kurativer Absicht reseziert werden können. Die Patienten müssen über ausreichend Tumorgewebe verfügen und alle Aufnahmekriterien erfüllen, um eingeschlossen zu werden.
- Frauen oder Männer, die zum Zeitpunkt der Einwilligung 18 Jahre alt sind.
- Bereitschaft und Fähigkeit, alle studienbezogenen Untersuchungen, einschließlich PRO-Bewertungen, nach Ermessen des Prüfers durchzuführen.
- Messbare Erkrankung nach RECIST v1.1
Zuvor bestrahlte Läsionen können nur dann als messbare Krankheit bewertet werden, wenn die fortschreitende Erkrankung seit der Bestrahlung eindeutig dokumentiert ist.
- Eastern Cooperative Oncology Group (ECOG) Leistungsstatus von 0 oder 1
- Ausreichende hämatologische und Organfunktion innerhalb von 14 Tagen vor der ersten Studienbehandlung
- Patient ist geeignet für eine Paclitaxel-Monotherapie bei unbekanntem oder nicht-positivem PD-L1-Status des Tumors bzw. für Paclitaxel und Atezolizumab bei positivem PD-L1-Status des Tumors.
- Histologisch dokumentiertes dreifach-negatives Adenokarzinom der Brust, das lokal fortgeschritten oder metastasierend ist und nicht mit kurativer Absicht resezierbar ist.

Exclusion criteria (Data source: BASEC)

- Vorgeschichte eines Malabsorptionssyndroms oder einer anderen Erkrankung, die die enterale Absorption stören würde oder die zur Unfähigkeit oder mangelnden Bereitschaft führt, Tabletten zu schlucken.
- Aktive Infektion, die eine systemische antimikrobielle Behandlung erfordert (einschließlich Antibiotika, Antimykotika und antivirale Medikamente).
- Bekannte HIV-Infektion (es muss ein negativer HIV-Test beim Screening vorliegen).
- Bekannte klinisch signifikante Vorgeschichte einer Lebererkrankung entsprechend Child-Pugh Klasse B oder C, einschließlich aktiver viraler oder anderer Hepatitis (z.B. positiv für Hepatitis-B-Oberflächenantigen [HBsAg] oder Hepatitis-C-Virus [HCV]-Antikörper beim Screening), aktueller Drogen- oder Alkoholmissbrauch oder Leberzirrhose.
- Aktuelle Behandlung mit antiviraler Therapie für HBV.
- Größerer chirurgischer Eingriff, offene Biopsie oder schwere traumatische Verletzung innerhalb von 28 Tagen vor Tag 1 des Zyklus 1 oder voraussichtliche Erfordernis eines größeren chirurgischen Eingriffs während der Studie.
- Erfordernis einer chronischen Kortikosteroidtherapie von >10 mg Prednison pro Tag oder einer äquivalenten Dosis anderer entzündungshemmender Kortikosteroide oder Immunsuppressiva für eine chronische Erkrankung.
- Vorgeschichte oder bekanntes Vorhandensein von Rückenmarksmetastasen, festgestellt durch Computertomographie (CT) oder Magnetresonanztomographie (MRT) während des Screenings oder früherer radiologischer Untersuchungen.
- Bekannte BRCA1/2 schädigende Keimbahnmutation, es sei denn, der Patient ist kein geeigneter Kandidat für einen PARP-Hemmer.
- Jede frühere systemische Therapie bei inoperablem, lokal fortgeschrittenem oder metastasierendem dreifach negativem Adenokarzinom der Brust.

Inclusion/Exclusion Criteria (Data source: WHO)


Inclusion Criteria:

1. Willingness and ability to complete all study-related assessments, including PRO
assessments, in the investigator's judgement.

2. Adequate hematologic and organ function within 14 days before the first study
treatment on Day 1 of Cycle 1.

3. Life expectancy of at least 6 months.

4. Measurable disease according to RECIST v1.1.

5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.

6. For women of childbearing potential: agreement to remain abstinent (refrain from
heterosexual intercourse) or use contraception, and agreement to refrain from donating
eggs.

7. For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use
contraceptive methods, and agreement to refrain from donating sperm.

8. Appropriate candidate for paclitaxel monotherapy if tumor PD-L1 status is unknown or
non-positive; appropriate candidate for paclitaxel and atezolizumab if tumor PD-L1
status is positive.

9. Histologically documented triple-negative adenocarcinoma of the breast that is locally
advanced or metastatic and is not amenable to resection with curative intent.

Exclusion Criteria:

1. Inability to comply with study and follow-up procedures.

2. History of malabsorption syndrome or other condition that would interfere with enteral
absorption or results in the inability or unwillingness to swallow pills.

3. Severe infection within 4 weeks prior to initiation of study treatment (including, but
not limited to, hospitalization for complications of infection, bacteremia, or severe
pneumonia) as well as those who have received treatment with therapeutic oral or
intravenous (IV) antibiotics within 2 weeks prior to initiation of study treatment.

4. Known HIV infection (there must be a negative HIV test at screening).

5. Known clinically significant history of liver disease consistent with Child-Pugh Class
B or C.

6. Current treatment with anti-viral therapy for HBV.

7. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
prior to Day 1 of Cycle 1 or anticipation of need for a major surgical procedure
during the study.

8. Pregnancy or breastfeeding, or intention to become pregnant during the study or within
28 days after the final dose of ipatasertib/placebo, 5 months after the final dose of
atezolizumab/placebo, and 6 months after the final dose of paclitaxel whichever occurs
later.

9. New York Heart Association Class II, III, or IV heart failure, left ventricular
ejection fraction < 50%, or active ventricular arrhythmia requiring medication.

10. Current unstable angina or history of myocardial infarction within 6 months prior to
Day 1 of Cycle 1.

11. Congenital long QT syndrome or screening QT interval corrected through use
Fridericia's formula (QTcF) > 480 ms.

12. Current treatment with medications used at doses known to cause clinically relevant
prolongation of QT/QTc interval.

13. History or presence of an abnormal ECG that is clinically significant in the
investigator's opinion (including complete left bundle branch block, second- or
third-degree heart block, or evidence of prior myocardial infarction).

14. Requirement for chronic corticosteroid therapy of > 10 mg of prednisone per day or an
equivalent dose of other anti-inflammatory corticosteroids or immunosuppressant agents
for a chronic disease.

15. Treatment with approved or investigational cancer therapy within 14 days prior to Day
1 of Cycle 1.

16. Any other disease, metabolic dysfunction, physical examination finding, or clinical
laboratory finding that, in the investigator's opinion, gives reasonable suspicion of
a disease or condition that contraindicates the use of an investigational drug or that
may affect the interpretation of the results or renders the participant at high risk
from treatment complications.

17. History of or known presence of spinal cord metastases, as determined by computed
tomography (CT) or magnetic resonance imaging (MRI) evaluation during screening or
prior radiographic assessments.

18. Known CNS disease, except for treated asymptomatic CNS metastases.

19. Known germline BRCA1/2 deleterious mutation, unless the participant is not an
appropriate candidate for a PARP-inhibitor.

20. Any previous systemic therapy for inoperable locally advanced or metastatic
triple-negative adenocarcinoma of the breast.

21. Unresolved, clinically significant toxicity from prior therapy, except for alopecia
and Grade 1 peripheral neuropathy.

22. Participants who have received palliative radiotherapy to peripheral sites (e.g., bone
metastases) for pain control and whose last treatment was completed 14 days prior to
Day 1 of Cycle 1 may be enrolled in the study if they have recovered from all acute,
reversible effects (e.g., to Grade 1 or resolved by enrolment).

23. Uncontrolled pleural effusion, pericardial effusion or ascites.

24. Uncontrolled tumor-related pain.

25. Malignancies other than breast cancer within 5 years prior to Day 1 of Cycle 1, except
for appropriately treated carcinoma in situ of the cervix, non-melanoma skin
carcinoma, or Stage I uterine cancer.

26. Known hypersensitivity or contraindication to any component of the study treatments,
including the paclitaxel excipient, macrogolglycerol ricinoleate.

27. Grade >= 2 peripheral neuropathy.

28. History of Type I or Type II diabetes mellitus requiring insulin.

29. Grade >= 2 uncontrolled or untreated hypercholesterolemia or hypertriglyceridemia.

30. History of or active inflammatory bowel disease (e.g., Crohn disease and ulcerative
colitis) or active bowel inflammation (e.g., diverticulitis).

31. Lung disease: pneumonitis, interstitial lung disease, idiopathic pulmonary fibrosis,
cystic fibrosis, Aspergillosis, active tuberculosis, or history of opportunistic
infections (pneumocystis pneumonia or cytomegalovirus pneumonia).

32. Treatment with strong CYP3A inhibitors or strong CYP3A inducers within 2 weeks or 5
drug-elimination half-lives, whichever is longer, prior to initiation of study drug.

33. Prior treatment with an Akt inhibitor.

34. Active or history of autoimmune disease or immune deficiency.

35. History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis
obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active
pneumonitis on screening chest CT scan.

36.

Further information on the trial in WHO primary registry

https://clinicaltrials.gov/show/NCT04177108

Further information on the trial from WHO database (ICTRP)

http://apps.who.int/trialsearch/Trial2.aspx?TrialID=NCT04177108

Further information on trial

Date trial registered

07.11.2019

Incorporation of the first participant

25.11.2019

Recruitment status

Active, not recruiting

Academic title (Data source: WHO)

A Phase III, Double-blind, Placebo-controlled, Randomized Study Of Ipatasertib in Combination With Atezolizumab and Paclitaxel as a Treatment for Participants With Locally Advanced Unresectable or Metastatic Triple-Negative Breast Cancer.

Type of trial (Data source: WHO)

Interventional

Design of the trial (Data source: WHO)

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

Phase (Data source: WHO)

Phase 3

Primary end point (Data source: WHO)

Overall Survival (OS);Investigator-assessed Progression Free Survival (PFS)

Secundary end point (Data source: WHO)

Percentage of Participants with Adverse Events (AEs)

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)

Basel, Zurich

Countries (Data source: WHO)

Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, China, Colombia, Costa Rica, Czechia, Denmark, Finland, France, Greece, Hong Kong, Hungary, India, Ireland, Israel, Italy, Japan, Korea, Mexico, New Zealand, Peru, Poland, Portugal, Republic of, Romania, Russian Federation, Serbia, Singapore, South Africa, Spain, Switzerland, Taiwan, Thailand, Turkey, Ukraine, United Kingdom, United States

Contact for further information on the trial

Details of contact in Switzerland (Data source: BASEC)

Clinical Trials
+41 61 715 43 55
switzerland.clinical-research@roche.com

Contact for general information (Data source: WHO)

Clinical Trials
Hoffmann-La Roche

Contact for scientific information (Data source: WHO)

Clinical Trials
Hoffmann-La Roche

Principal Sponsor/Investigator

Principal sponsor (Data source: WHO)

Hoffmann-La Roche

Authorisation by the ethics committee (Data source: BASEC)

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

Ethikkommission Nordwest- und Zentralschweiz EKNZ

Date of authorisation by the ethics committee

04.12.2019

Further trial identification numbers

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

2019-01946

Secondary ID (Data source: WHO)

2019-000810-12
CO41101