Active, not recruiting
Phase 3
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)
Condition(s) studied
Endometrial Neoplasms
Investigational drug(s) / intervention(s)
PembrolizumabCarboplatinPaclitaxelPlacebo for pembrolizumabDocetaxelCisplatinExternal Beam Radiotherapy (EBRT)Cisplatin (as radiosensitizer)Brachytherapy
Pembrolizumab: IV infusion
Carboplatin: IV infusion
Paclitaxel: IV infusion
Placebo for pembrolizumab: IV infusion
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.
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.
External Beam Radiotherapy (EBRT): ≥4500 cGY given according to local practice, at the discretion of the investigator
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
Brachytherapy: Given according to local practice, at the discretion of the investigator
Study summary
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.
Eligibility
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.
Primary outcome measure(s)
- Disease-Free Survival (DFS) as Assessed Radiographically by Investigator or by Histopathologic Confirmation of Suspected Disease Recurrence — Up to approximately 42 months
DFS is defined as the time from randomization to the first documented local recurrence, distant metastasis, secondary systemic malignancy, or death due to any cause, whichever occurs first. The DFS as assessed radiographically by investigator or by histopathologic confirmation of suspected disease recurrence, will be presented.
- Overall Survival (OS) — Up to approximately 54 months
OS is defined as the time from randomization to death due to any cause.
Trial sites (231)
| Facility | City | Region | Status |
| University of Alabama - Birmingham ( Site 3061) |
Birmingham |
Alabama |
|
| University of South Alabama, Mitchell Cancer Institute ( Site 3058) |
Mobile |
Alabama |
|
| HonorHealth Research Institute - Biltmore ( Site 3043) |
Phoenix |
Arizona |
|
| Arizona Oncology Associates PC- HOPE ( Site 3049) |
Tucson |
Arizona |
|
| UCSD Moores Cancer Center ( Site 3053) |
La Jolla |
California |
|
| University Of Colorado ( Site 3051) |
Aurora |
Colorado |
|
| Smilow Cancer Hospital at Yale New Haven ( Site 3070) |
New Haven |
Connecticut |
|
| Mount Sinai Cancer Center ( Site 3081) |
Miami Beach |
Florida |
|
| Northside Hospital ( Site 3036) |
Atlanta |
Georgia |
|
| Northwestern Memorial Hospital ( Site 3044) |
Chicago |
Illinois |
|
| Parkview Cancer Institute ( Site 3067) |
Fort Wayne |
Indiana |
|
| Indiana University Melvin and Bren Simon Cancer Center ( Site 3071) |
Indianapolis |
Indiana |
|
| University of Iowa Hospital and Clinics ( Site 3046) |
Iowa City |
Iowa |
|
| Norton Cancer Institute - St. Matthews ( Site 3056) |
Louisville |
Kentucky |
|
| WK Physicians Network/Gynecologic Oncology Associates ( Site 3047) |
Shreveport |
Louisiana |
|
| University of Massachusetts Medical School-Division of Gynecologic Oncology ( Site 3037) |
Worcester |
Massachusetts |
|
| Perlmutter Cancer Center at NYU Langone Hospital - Long Island ( Site 3076) |
Mineola |
New York |
|
| Laura and Isaac Perlmutter Cancer Center at NYU Langone Health ( Site 3042) |
New York |
New York |
|
| Montefiore Medical Center ( Site 3065) |
The Bronx |
New York |
|
| Duke Cancer Center ( Site 3072) |
Durham |
North Carolina |
|
| Sanford Fargo Medical Center-Roger Maris Cancer Center ( Site 3080) |
Fargo |
North Dakota |
|
| The James Cancer Hospital and Solove Research Institute at The Ohio State University Comprehensive C ( Site 3066) |
Columbus |
Ohio |
|
| Legacy Good Samaritan Medical Center ( Site 3033) |
Portland |
Oregon |
|
| Sidney Kimmel Cancer Center - Jefferson Health ( Site 3078) |
Philadelphia |
Pennsylvania |
|
| AHN West Penn Hospital ( Site 3060) |
Pittsburgh |
Pennsylvania |
|
| Abington Hospital - Asplundh Cancer Center ( Site 3073) |
Willow Grove |
Pennsylvania |
|
| Sanford Gynecology Oncology ( Site 3045) |
Sioux Falls |
South Dakota |
|
| UT Southwestern Medical Center ( Site 3063) |
Dallas |
Texas |
|
| VCU Massey Cancer Center ( Site 3068) |
Richmond |
Virginia |
|
| Centro de Oncología e Investigación de Buenos Aires ( Site 1005) |
Berazategui |
Buenos Aires |
|
| IDIM Instituto de Diagnostico e Investigaciones Metabolicas ( Site 1006) |
CABA |
Buenos Aires |
|
| CEMIC ( Site 1009) |
CABA |
Buenos Aires |
|
| Hospital Britanico de Buenos Aires ( Site 1002) |
Ciudad Autónoma de Buenos Aires |
Buenos Aires |
|
| Instituto de Investigaciones Clinicas Mar del Plata ( Site 1003) |
Mar del Plata |
Buenos Aires |
|
| Instituto de Oncologia de Rosario ( Site 1004) |
Rosario |
Santa Fe Province |
|
| IDIM - Instituto de Diagnóstico e Investigaciones Metabólicas ( Site 1010) |
Buenos Aires |
Argentina |
|
| Hospital Aleman ( Site 1001) |
Buenos Aires |
Argentina |
|
| Centro Oncologico Riojano Integral ( Site 1007) |
La Rioja |
Argentina |
|
| Medizinische Universitat Graz ( Site 2004) |
Graz |
Styria |
|
| Medizinische Universitaet Innsbruck ( Site 2001) |
Innsbruck |
Tyrol |
|
+ 191 more sites — see the full list on the official registry below.
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