Clinical Trials List
Protocol NumberMK-3475-A18/ENGOT-cx11
NCT Number(ClinicalTrials.gov Identfier)NCT04221945
Not yet recruiting
2020-03-01 - 2025-03-31
Phase III
Recruiting3
A Randomized, Phase 3, Double-Blind Study of Chemoradiotherapy With or Without Pembrolizumab for the Treatment of High-risk, Locally Advanced Cervical Cancer (KEYNOTE-A18/ENGOT-cx11/GOG-3047)
-
Trial Applicant
Merck Sharp & Dohme (I.A.) LLC
-
Sponsor
Merck Sharp & Dohme Corp.
-
Trial scale
Multi-Regional Multi-Center
-
Update
2026/02/01
Investigators and Locations
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 周宏學 Division of Obstetrics & Gynecology
- Cheng-Tao Lin Division of Obstetrics & Gynecology
- 黃意婷 Division of Radiation Therapy
- Huei-Jean Huang Division of Obstetrics & Gynecology
- 黃彥綾 Division of Radiology
- Yun-Hsin Tang Division of Obstetrics & Gynecology
- Chyong-Huey Lai Division of Obstetrics & Gynecology
- Angel Chao Division of Obstetrics & Gynecology
- Chun-Chieh Wang Division of Radiation Therapy
- 黃寬仁 Division of Obstetrics & Gynecology
- 陳威君 Division of Obstetrics & Gynecology
- 江盈瑩 Division of Radiation Therapy
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 陳祈安 Division of Obstetrics & Gynecology
- 陳宇立 Division of Obstetrics & Gynecology
- 許哲瑜 Division of Radiation Therapy
- CHI-HAU CHEN CHI-HAU CHEN Division of Obstetrics & Gynecology
- 郭冠廷 Division of Others
- YING-CHENG CHIANG Division of Obstetrics & Gynecology
- 陳苓諭 Division of Radiation Therapy
- 童寶玲 Division of Obstetrics & Gynecology
- 施怡倫 Division of Radiology
- 戴依柔 Division of Obstetrics & Gynecology
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
Locally Advanced Cervical Cancer
Objectives
The purpose of this study is to evaluate the efficacy and safety of pembrolizumab plus concurrent chemoradiotherapy compared to placebo plus concurrent chemoradiotherapy in participants with locally advanced cervical cancer.
The primary hypotheses are that pembrolizumab plus concurrent chemoradiotherapy is superior to placebo plus concurrent chemoradiotherapy with respect to progression-free survival and overall survival.
Once the study objectives have been met or the study has ended, participants will be discontinued from this study and will be enrolled in an extension study to continue protocol-defined assessments and treatment.
Test Drug
Pembrolizumab (MK-3475)
Pembrolizumab (MK-3475)
Pembrolizumab (MK-3475)
Active Ingredient
Pembrolizumab (Humanized anti-PD-1 mAb)
Dosage Form
Injection
Dosage
100 mg/ 4 mL
Endpoints
Primary Outcome Measures :
Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by the Investigator [ Time Frame: Up to approximately 38 months ]
PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, or by histopathologic confirmation of disease progression, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. Unequivocal progression of non-target lesions is also considered PD.
Overall Survival (OS) [ Time Frame: Up to approximately 46 months ]
OS is the time from randomization to death due to any cause.
Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by the Investigator [ Time Frame: Up to approximately 38 months ]
PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, or by histopathologic confirmation of disease progression, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. Unequivocal progression of non-target lesions is also considered PD.
Overall Survival (OS) [ Time Frame: Up to approximately 46 months ]
OS is the time from randomization to death due to any cause.
Inclution Criteria
Inclusion Criteria:
Has high-risk locally advanced cervical cancer (LACC): The International Federation of Gynecology and Obstetrics (FIGO) 2014 Stage IB2-IIB (with node-positive disease) or FIGO 2014 Stages III-IVA
Has histologically-confirmed squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the cervix
Has not previously received any definitive surgical, radiation, or systemic therapy for cervical cancer, including investigational agents, and is immunotherapy-naïve
Female participants must not be pregnant or breastfeeding, and agree to use highly effective contraception during the treatment period and for at least 120 days after the last dose of pembrolizumab or placebo and 180 days following the end of chemoradiotherapy and agrees not to donate eggs (ova, oocytes) to others or freeze/store for her own use for the purpose of reproduction during this period
Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days prior to the first dose of study treatment
Has provided a tissue sample from a core or excisional biopsy of a tumor lesion
Has radiographically evaluable disease, either measurable or non-measurable per RECIST 1.1, as assessed by the local site investigator/radiology
Has adequate organ within 7 days prior to the start of study treatment
Has high-risk locally advanced cervical cancer (LACC): The International Federation of Gynecology and Obstetrics (FIGO) 2014 Stage IB2-IIB (with node-positive disease) or FIGO 2014 Stages III-IVA
Has histologically-confirmed squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the cervix
Has not previously received any definitive surgical, radiation, or systemic therapy for cervical cancer, including investigational agents, and is immunotherapy-naïve
Female participants must not be pregnant or breastfeeding, and agree to use highly effective contraception during the treatment period and for at least 120 days after the last dose of pembrolizumab or placebo and 180 days following the end of chemoradiotherapy and agrees not to donate eggs (ova, oocytes) to others or freeze/store for her own use for the purpose of reproduction during this period
Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days prior to the first dose of study treatment
Has provided a tissue sample from a core or excisional biopsy of a tumor lesion
Has radiographically evaluable disease, either measurable or non-measurable per RECIST 1.1, as assessed by the local site investigator/radiology
Has adequate organ within 7 days prior to the start of study treatment
Exclusion Criteria
Exclusion Criteria:
Has excluded subtypes of LACC
Has FIGO 2014 Stage IVB disease
Has undergone a previous hysterectomy defined as removal of the entire uterus or will have a hysterectomy as part of their initial cervical cancer therapy
Has bilateral hydronephrosis, unless at least one side has been stented or resolved by positioning of nephrostomy or considered mild and not clinically significant in the opinion of the investigator
Has anatomy or tumor geometry or any other reason or contraindication that cannot be treated with intracavitary brachytherapy or a combination of intracavitary and interstitial brachytherapy
Has received a live vaccine within 30 days prior to the first dose of study treatment
Has received treatment with systemic immunostimulatory agents, colony stimulating factors, interferons, interleukins and vaccine combinations within 6 weeks or 5 half-lives of the drug, whichever is shorter, prior to Cycle 1, Day 1
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 prior systemic anticancer therapy including investigational agents within 4 weeks prior to randomization
Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to randomization
Has any contraindication to the use of cisplatin.
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 to the first dose of study treatment
Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
Has severe hypersensitivity to pembrolizumab and/or any of its excipients
Has an active autoimmune disease that has required systemic treatment in past 2 years
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 Human Immunodeficiency Virus (HIV) infection
Has a known history of Hepatitis B or known active Hepatitis C virus infection
Has a history or current evidence of any condition, therapy, lab abnormality, or other circumstance that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results, and in the judgment of the investigator or Sponsor, would make the participant inappropriate for entry into this study
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 evidence of metastatic disease per RECIST 1.1 including lymph nodes above the first lumbar vertebra (L1) cephalad body, in the inguinal region
Has excluded subtypes of LACC
Has FIGO 2014 Stage IVB disease
Has undergone a previous hysterectomy defined as removal of the entire uterus or will have a hysterectomy as part of their initial cervical cancer therapy
Has bilateral hydronephrosis, unless at least one side has been stented or resolved by positioning of nephrostomy or considered mild and not clinically significant in the opinion of the investigator
Has anatomy or tumor geometry or any other reason or contraindication that cannot be treated with intracavitary brachytherapy or a combination of intracavitary and interstitial brachytherapy
Has received a live vaccine within 30 days prior to the first dose of study treatment
Has received treatment with systemic immunostimulatory agents, colony stimulating factors, interferons, interleukins and vaccine combinations within 6 weeks or 5 half-lives of the drug, whichever is shorter, prior to Cycle 1, Day 1
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 prior systemic anticancer therapy including investigational agents within 4 weeks prior to randomization
Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to randomization
Has any contraindication to the use of cisplatin.
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 to the first dose of study treatment
Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
Has severe hypersensitivity to pembrolizumab and/or any of its excipients
Has an active autoimmune disease that has required systemic treatment in past 2 years
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 Human Immunodeficiency Virus (HIV) infection
Has a known history of Hepatitis B or known active Hepatitis C virus infection
Has a history or current evidence of any condition, therapy, lab abnormality, or other circumstance that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results, and in the judgment of the investigator or Sponsor, would make the participant inappropriate for entry into this study
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 evidence of metastatic disease per RECIST 1.1 including lymph nodes above the first lumbar vertebra (L1) cephalad body, in the inguinal region
The Estimated Number of Participants
-
Taiwan
12 participants
-
Global
980 participants
