Study of Pembrolizumab (MK-3475) in Combination With Adjuvant Chemotherapy With or Without Radiotherapy in Participants With Newly Diagnosed Endometrial Cancer After Surgery With Curative Intent (MK-3475-B21 / KEYNOTE-B21 / ENGOT-en11 / GOG-3053)
Фаза 3 – широко изпитване преди одобрение
Заболявания:
Endometrial Neoplasms
Спонсор: Merck Sharp & Dohme LLC
Налично на:
БГ
Обобщение
The purpose of this study is to compare pembrolizumab + adjuvant chemotherapy with placebo + adjuvant chemotherapy, with or without radiotherapy, with respect to disease-free survival (DFS) as assessed radiographically by the investigator or by histopathologic confirmation of suspected disease recurrence, and with respect to overall survival (OS). The primary hypotheses are that pembrolizumab + adjuvant chemotherapy is superior to placebo + adjuvant chemotherapy, with or without radiotherapy, with respect to DFS as assessed radiographically by the investigator or by histopathologic confirmation of suspected disease recurrence, and with respect to OS.
Кой може да участва
Inclusion Criteria:
* Has a histologically confirmed new diagnosis of Endometrial Carcinoma or Carcinosarcoma (Mixed Mullerian Tumor) and:
* Has undergone curative intent surgery that included hysterectomy and bilateral salpingo-oophorectomy; and
* Is at high risk for recurrence following treatment with curative intent surgery, ie: Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) 2009 surgical stage I/II with myometrial invasion of non-endometrioid histology; FIGO 2009 surgical stage I/II with myometrial invasion of any histology with known aberrant p53 expression or p53 mutation; or FIGO (2009) surgical stage III or IVA of any histology.
* Is disease-free with no evidence of loco-regional disease or distant metastasis post operatively and on imaging.
* Has not received any radiation or systemic therapy, including immunotherapy, hormonal therapy, or hyperthermic intraperitoneal chemotherapy (HIPEC), in any setting including the neoadjuvant setting for endometrial cancer (EC).
* Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days before randomization.
* Submission of a tumor tissue sample from current diagnosis of Endometrial Carcinoma or Carcinosarcoma for prospective determination of histology and mismatch repair (MMR) status by central vendor is required for all participants.
* Has adequate organ function within 7 days of randomization.
Exclusion Criteria:
* Has recurrent endometrial carcinoma or carcinosarcoma.
* Has uterine mesenchymal tumor such as an endometrial stromal sarcoma, leiomyosarcoma, or other types of pure sarcomas. Adenosarcomas are also not allowed.
* Has FIGO (2009) Surgical Stage I/II EC of endometrioid histology without a known aberrant p53 expression or p53 mutation.
* Is known to have a deoxyribonucleic acid (DNA) polymerase epsilon catalytic subunit A (POLE) mutation.
* Has FIGO Stage IVB disease of any histology even if there is no evidence of disease after surgery.
* Has residual tumor whether measurable or non-measurable after surgery.
* Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 3 years.
* Note: The time requirement does not apply to participants who underwent successful definitive resection of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, in situ cervical cancer, or other in situ cancers.
* Has received prior therapy with an anti-programmed cell death receptor 1 (PD-1), anti-programmed cell death receptor ligand 1 (PD-L1), or anti-programmed cell death receptor ligand 2 (PD-L2) agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), OX-40, CD137).
* Has received a live vaccine within 30 days before the first dose of study intervention.
* Note: killed vaccines are allowed.
* Has a known intolerance to study intervention (or any of the excipients).
* Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study intervention.
* Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
* Has any contraindication to the use of carboplatin or paclitaxel.
* Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study intervention.
* Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
* Has an active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
* Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
* Has an active infection requiring systemic therapy.
* Has a known history of HIV infection.
* Has a known history of Hepatitis B or known active Hepatitis C virus infection.
* Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study.
* Has had an allogenic tissue/solid organ transplant.
* Has not recovered adequately from surgery and/or any complications from the surgery.
* Is breastfeeding.
Места на провеждане
27
Argentina (1)
Centro de Oncología e Investigación de Buenos Aires ( Site 1005)
Berazategui , Buenos Aires
Австрия (1)
Medizinische Universitat Graz ( Site 2004)
Graz , Styria
Белгия (1)
Saint-Luc UCL ( Site 2042)
Brussels , Bruxelles-Capitale, Region de
Канада (1)
Tom Baker Cancer Centre ( Site 3007)
Calgary , Alberta
Chile (1)
Centro Investigación del Cáncer James Lind ( Site 1061)
Temuco , Araucania
Китай (1)
Anhui Provincial Hospital-Obstetrics and Gynecology ( Site 4034)
Hefei , Anhui
Colombia (1)
Clínica Vida Fundación - Sede Poblado ( Site 1096)
Medellín , Antioquia
Чехия (1)
Fakultní nemocnice Brno Bohunice-Gynekologicko-porodnicka klinika ( Site 2394)
Brno , Brno-mesto
Дания (1)
Rigshospitalet University Hospital ( Site 2515)
Copehagen , Capital Region
Финландия (1)
Kuopio University Hospital ( Site 2543)
Kuopio , Northern Savonia
Франция (1)
Institut De Cancerologie De Lorraine ( Site 2072)
Vandœuvre-lès-Nancy , Ain
Гърция (1)
General Hospital of Patras. St Andrews ( Site 2421)
Pátrai , Achaia
Израел (1)
Rambam Medical Center ( Site 2307)
Haifa
Италия (1)
Istittuto Nazionale dei Tumori Regina Elena IRCCS - IFO ( Site 2121)
Roma , Abruzzo
Япония (1)
Aichi Cancer Center Hospital ( Site 4190)
Nagoya , Aichi-ken
Mexico (1)
Investigacion Onco Farmaceutica S de RL de CV ( Site 1127)
La Paz , Baja California Sur
Норвегия (1)
University Hospital of North Norway ( Site 2153)
Tromsø , Troms
Полша (1)
Wielkopolskie Centrum Onkologii im.M.Sklodowskiej-Curie ( Site 2484)
Poznan , Greater Poland Voivodeship
Russia (1)
Arkhangelsk Clinical Oncological Dispensary ( Site 2637)
Arkhangelsk , Arkhangelskaya oblast
Южна Корея (1)
National Cancer Center ( Site 4065)
Goyang-si , Kyonggi-do
Испания (1)
Hospital Josep Trueta ( Site 2184)
Girona , Gerona
Швеция (1)
Karolinska Universitetssjukhuset Solna ( Site 2220)
Solna , Stockholm County
Taiwan (1)
Changhua Christian Hospital ( Site 4095)
Changhua
Турция (1)
Baskent Adana Dr Turgut Noyan Uygulama ve Arastirma Merkezi ( Site 2355)
Adana
Ukraine (1)
Chernihiv Medical Center of Modern Oncology ( Site 2368)
Chernihiv , Chernihiv Oblast
Великобритания (1)
Bristol Haematology and Oncology Centre ( Site 2244)