Cervical cancer MedDRA version: 20.0 Level: LLT Classification code 10008229 Term: Cervical cancer System Organ Class: 100000004864
Conditions
Sponsors
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Female participants who are at least 18 years of age on the day of signing informed consent 2. Have persistent, recurrent, or metastatic squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix which has not been treated with systemic chemotherapy and is not amenable to curative treatment (such as with surgery and/or radiation) 3. Not be pregnant or breastfeeding, and at least one of the following conditions applies: a. Not be a woman of childbearing potential (WOCBP) b. A WOCBP must agree to use contraception during the treatment period and for at least 120 days after the last dose of pembrolizumab/placebo or 210 days after the last dose of chemotherapy 4. The participant (or legally acceptable representative if applicable) provides written informed consent for the study. The participant may also provide consent for future biomedical research. However, the participant may participate in the main study without participating in future biomedical research 5. Have measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology. Lesions situated in a previously irradiated area are considered measurable only if progression has been demonstrated in such lesions 6. Have provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated for prospective determination of PD-L1 status prior to randomization 7. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within 14 days prior to randomization 8. Have adequate organ function Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 600 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. A WOCBP who has a positive urine pregnancy test within 72 hours prior to randomization. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required 2. Has known active CNS metastases and/or carcinomatous meningitis. Participants with known brain metastases may participate provided that the brain metastases have been previously treated (except with chemotherapy) and are radiographically stable. To demonstrate radiographic stability of previously treated brain metastases, a minimum of 2 post-treatment brain imaging assessments are required: 1) The first brain imaging must be acquired after treatment of brain metastases has been completed 2) The second brain imaging must be obtained during screening (i.e. within 28 days prior to randomization) and >4 weeks after the previous post-treatment brain imaging 3. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years 4. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in doses exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to randomization 5. 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 6. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis 7. Has an active infection requiring systemic therapy 8. Has a known history of human immunodeficiency virus (HIV) infection 9. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection 10. Has a known history of active tuberculosis (TB; Bacillus tuberculosis) 11. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PDL2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137) 12. Has received prior systemic chemotherapy for treatment of cervical cancer (chemotherapy used as a radiosensitizing agent and completed at least 2 weeks prior to randomization is permitted) 13. Has not recovered adequately from toxicity and/or complications from surgery prior to randomization 14. Has received prior radiotherapy within 2 weeks prior to randomization. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (=2 weeks of radiotherapy) to non-CNS disease 15. Has received a live vaccine within 30 days prior to randomization. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette–Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed 16. Has severe hypersensitivity (=Grade 3) to pembrolizumab and/or any of its excipients 17. Has a contraindication or hypersensitivity to
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To compare progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) as assessed by blinded independent central review (BICR) 2. To compare overall survival (OS);Secondary Objective: 1. To evaluate the objective response rate (ORR), duration of response (DOR), and 12-month PFS rate per RECIST 1.1 as assessed by BICR 2. To compare the safety and tolerability by the proportion of adverse events (AEs) 3. To evaluate changes in Health- Related Quality of Life (HRQoL) assessments using the global score of the European Organisation for the Research and Treatment of Cancer (EORTC) QLQ-C30;Primary end point(s): 1) Progression-free survival (PFS) based on RECIST 1.1 as assessed by BICR 2) Overall survival (OS);Timepoint(s) of evaluation of this end point: The first interim analysis (interim analysis for PFS and OS) will be conducted when approximated 182 PFS events have been observed for CPS =10 group. The second interim analysis (final PFS analysis and interim OS analysis ) may be conducted when at least 227 PFS events for CPS =10 group. The final analysis (final OS analysis) may be conducted when at least 184 OS events for CPS =10 group | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Objective response rate (ORR) by BICR using RECIST 1.1 2) Duration of response (DOR) by BICR using RECIST1.1 3) PFS rate at 12 months by BICR using RECIST 1.1 4) Patient reported quality of life by EORTC QLQ-C30 global score 5) Safety and tolerability of the two treatment arms | — |
Countries
Argentina, Australia, Canada, Chile, Colombia, France, Germany, Israel, Italy, Japan, Korea, Republic of, Mexico, Peru, Poland, Russian Federation, Spain, Taiwan, Turkey, Ukraine, United States
Contacts
Public ContactKaren Stein
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
Outcome results
None listed