Resumen

El propósito de este estudio es comparar pembrolizumab + quimioterapia adyuvante con placebo + quimioterapia adyuvante, con o sin radioterapia, con respecto a la supervivencia libre de enfermedad (DFS) evaluada radiográficamente por el investigador o mediante confirmación histopatológica de sospecha de recurrencia de la enfermedad, y con respecto a la supervivencia global (OS). Las hipótesis primarias son que pembrolizumab + quimioterapia adyuvante es superior a placebo + quimioterapia adyuvante, con o sin radioterapia, con respecto a la DFS evaluada radiográficamente por el investigador o mediante confirmación histopatológica de sospecha de recurrencia de la enfermedad, y con respecto a la OS.

Elegibilidad

Edad mínima: 18 YearsSexo: FEMALE

Criterios de inclusión

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.

Criterios de exclusión

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.

Intervenciones

biological

Pembrolizumab

IV infusion

drug

Carboplatin

IV infusion

drug

Paclitaxel

IV infusion

drug

Placebo for pembrolizumab

IV infusion

drug

Docetaxel

IV infusion docetaxel 75 mg/m\^2 Q3W or 25 mg/m2 QW may be given in place of paclitaxel following sponsor consultation if a participant experiences severe hypersensitivity to paclitaxel or an adverse event requiring discontinuation of paclitaxel.

drug

Cisplatin

Cisplatin 75 mg/m\^2 IV infusion Q3W may be given in place of carboplatin following sponsor consultation if a participant experiences severe hypersensitivity to carboplatin or an adverse event requiring discontinuation of carboplatin.

radiation

External Beam Radiotherapy (EBRT)

≥4500 cGY given according to local practice, at the discretion of the investigator

drug

Cisplatin (as radiosensitizer)

If a participant receives external beam radiotherapy (EBRT), then cisplatin 50 mg/m\^2 IV infusion may be administered as a radiosensitizer at the discretion of the investigator, on days 1 and 29

radiation

Brachytherapy

Given according to local practice, at the discretion of the investigator

Ubicaciones

Centro de Oncología e Investigación de Buenos Aires ( Site 1005)

Berazategui, Buenos Aires, Argentina

IDIM Instituto de Diagnostico e Investigaciones Metabolicas ( Site 1006)

Caba, Buenos Aires, Argentina

Instituto de Investigaciones Clinicas Mar del Plata ( Site 1003)

Mar del Plata, Buenos Aires, Argentina

Hospital Britanico de Buenos Aires ( Site 1002)

Buenos Aires, Buenos Aires F.D., Argentina

Instituto de Oncologia de Rosario ( Site 1004)

Rosario, Santa Fe Province, Argentina

IDIM - Instituto de Diagnóstico e Investigaciones Metabólicas ( Site 1010)

Buenos Aires, Argentina

Hospital Aleman ( Site 1001)

Buenos Aires, Argentina

CEMIC ( Site 1009)

Buenos Aires, Argentina

Centro Oncologico Riojano Integral ( Site 1007)

La Rioja, Argentina

Resumen

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Pembrolizumab

Carboplatin

Paclitaxel

Placebo for pembrolizumab

Docetaxel

Cisplatin

External Beam Radiotherapy (EBRT)

Cisplatin (as radiosensitizer)

Brachytherapy

Ubicaciones

Centro de Oncología e Investigación de Buenos Aires ( Site 1005)

IDIM Instituto de Diagnostico e Investigaciones Metabolicas ( Site 1006)

Instituto de Investigaciones Clinicas Mar del Plata ( Site 1003)

Hospital Britanico de Buenos Aires ( Site 1002)

Instituto de Oncologia de Rosario ( Site 1004)

IDIM - Instituto de Diagnóstico e Investigaciones Metabólicas ( Site 1010)

Hospital Aleman ( Site 1001)

CEMIC ( Site 1009)

Centro Oncologico Riojano Integral ( Site 1007)

Patrocinadores