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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03635567




Registration number
NCT03635567
Ethics application status
Date submitted
15/08/2018
Date registered
17/08/2018

Titles & IDs
Public title
Efficacy and Safety Study of First-line Treatment With Pembrolizumab (MK-3475) Plus Chemotherapy Versus Placebo Plus Chemotherapy in Women With Persistent, Recurrent, or Metastatic Cervical Cancer (MK-3475-826/KEYNOTE-826)
Scientific title
A Phase 3 Randomized, Double-Blind, Placebo-Controlled Trial of Pembrolizumab (MK-3475) Plus Chemotherapy Versus Chemotherapy Plus Placebo for the First-Line Treatment of Persistent, Recurrent, or Metastatic Cervical Cancer (KEYNOTE-826)
Secondary ID [1] 0 0
MK-3475-826
Secondary ID [2] 0 0
3475-826
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cervical Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Womb (Uterine or endometrial cancer)
Cancer 0 0 0 0
Cervical (cervix)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Pembrolizumab
Treatment: Drugs - Paclitaxel
Treatment: Drugs - Cisplatin
Treatment: Drugs - Carboplatin
Treatment: Other - Bevacizumab
Treatment: Drugs - Placebo to pembrolizumab

Experimental: Pembrolizumab+Chemotherapy - On Day 1 of each 21-day cycle, participants receive an intravenous (IV) infusion of pembrolizumab 200 mg for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m\^2 PLUS cisplatin 50 mg/m\^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m\^2 PLUS carboplatin Area Under the Curve (AUC) 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments are administered until disease progression or toxicity.

Placebo comparator: Placebo+Chemotherapy - On Day 1 of each 21-day cycle, participants receive an IV infusion of placebo (Normal Saline or Dextrose solution) for up to 35 cycles (up to approximately 2 years) PLUS Investigator choice of chemotherapy for up to 6 cycles (paclitaxel 175 mg/m\^2 PLUS cisplatin 50 mg/m\^2 WITH or WITHOUT bevacizumab 15 mg/kg per local label OR paclitaxel 175 mg/m\^2 PLUS carboplatin AUC 5 for up to 6 cycles, WITH or WITHOUT bevacizumab 15 mg/kg per local label). All treatments are administered until disease progression or toxicity.


Treatment: Other: Pembrolizumab
IV infusion

Treatment: Drugs: Paclitaxel
IV infusion

Treatment: Drugs: Cisplatin
IV infusion

Treatment: Drugs: Carboplatin
IV infusion

Treatment: Other: Bevacizumab
IV infusion

Treatment: Drugs: Placebo to pembrolizumab
IV infusion

Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Investigator in Participants With Programmed Cell Death-Ligand 1 (PD-L1) Combined Positive Score (CPS) =1
Timepoint [1] 0 0
Up to approximately 46 months
Primary outcome [2] 0 0
PFS Per RECIST 1.1 as Assessed by Investigator in All Participants
Timepoint [2] 0 0
Up to approximately 46 months
Primary outcome [3] 0 0
PFS Per RECIST 1.1 as Assessed by Investigator in Participants With PD-L1 CPS =10
Timepoint [3] 0 0
Up to approximately 46 months
Primary outcome [4] 0 0
Overall Survival (OS) in Participants With PD-L1 CPS =1
Timepoint [4] 0 0
Up to approximately 46 months
Primary outcome [5] 0 0
OS in All Participants
Timepoint [5] 0 0
Up to approximately 46 months
Primary outcome [6] 0 0
OS in Participants With PD-L1 CPS =10
Timepoint [6] 0 0
Up to approximately 46 months
Secondary outcome [1] 0 0
Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by Investigator
Timepoint [1] 0 0
Up to approximately 46 months
Secondary outcome [2] 0 0
Duration of Response (DOR) Per RECIST 1.1 as Assessed by Investigator
Timepoint [2] 0 0
Up to approximately 46 months
Secondary outcome [3] 0 0
Percentage of Participants That Were PFS Event-Free (PFS Rate) at Month 12 Per RECIST 1.1 as Assessed by Investigator
Timepoint [3] 0 0
12 months
Secondary outcome [4] 0 0
PFS Per RECIST 1.1 as Assessed by Blinded Independent Central Review (BICR)
Timepoint [4] 0 0
Up to approximately 46 months
Secondary outcome [5] 0 0
Number of Participants Who Experienced an Adverse Event (AE)
Timepoint [5] 0 0
Up to approximately 46 months
Secondary outcome [6] 0 0
Number of Participants Who Experienced a Serious AE (SAE)
Timepoint [6] 0 0
Up to approximately 46 months
Secondary outcome [7] 0 0
Number of Participants Who Experienced an Immune-related AE (irAE)
Timepoint [7] 0 0
Up to approximately 46 months
Secondary outcome [8] 0 0
Number of Participants Who Discontinued Study Treatment Due to an AE
Timepoint [8] 0 0
Up to approximately 43 months
Secondary outcome [9] 0 0
Number of Participants With a 10-point Change From Baseline in Quality of Life (QoL) Based on the European Organisation for the Research & Treatment of Cancer (EORTC) QoL Questionnaire-30 (QLQ-C30) Combined Global Score
Timepoint [9] 0 0
Baseline (Cycle 1 Day 1: Predose) and up to approximately 46 months

Eligibility
Key inclusion criteria
* Has 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). Prior chemotherapy utilized as a radiosensitizing agent and completed at least 2 weeks prior to randomization with resolution of all treatment-related toxicities is allowed. AEs due to previous treatments should be resolved to = Grade 1 or baseline. Participants with = Grade 2 neuropathy or = Grade 2 alopecia are eligible.
* Not pregnant or breastfeeding, and at least one of the following conditions applies: a.) Not a woman of childbearing potential (WOCBP), b.) A WOCBP must agree to use effective contraception during the treatment period and for at least 120 days after the last dose of pembrolizumab/placebo and 210 days after the last dose of chemotherapy/bevacizumab
* Has measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology
* Has provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated for prospective determination of Programmed Cell Death-Ligand 1 (PD-L1) status prior to randomization
* Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within 14 days prior to randomization
* Has adequate organ function
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
* A WOCBP who has a positive urine pregnancy test within 72 hours prior to randomization
* Has known active central nervous system (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.
* Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, transitional cell carcinoma of urothelial cancer, or carcinoma in situ (e.g. breast cancer) that have undergone potentially curative therapy are not excluded.
* 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
* Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. 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 human immunodeficiency virus (HIV) infection
* Has a known history of Hepatitis B or known active Hepatitis C virus infection
* Has a known history of active tuberculosis (TB; Bacillus tuberculosis)
* Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g. cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX 40, CD137)
* Has received prior systemic chemotherapy for treatment of cervical cancer.
* Has not recovered adequately from toxicity and/or complications from major surgery prior to randomization
* 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.
* Has received a live vaccine within 30 days prior to randomization
* Has severe hypersensitivity (=Grade 3) to pembrolizumab and/or any of its excipients.
* Has a contraindication or hypersensitivity to any component of cisplatin, carboplatin, paclitaxel, or bevacizumab
* 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
* Is pregnant or breastfeeding or expecting to conceive within the projected duration of the study, starting with the screening visit through 120 days following last dose of pembrolizumab/placebo and 210 days following last dose of chemotherapy/bevacizumab
* Has had an allogeneic tissue/solid organ transplant

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,WA
Recruitment hospital [1] 0 0
Royal North Shore Hospital ( Site 1514) - St Leonards
Recruitment hospital [2] 0 0
Mater Misericordiae Ltd Mater Cancer Care Centre ( Site 1521) - South Brisbane
Recruitment hospital [3] 0 0
Flinders Medical Centre ( Site 1513) - Bedford Park
Recruitment hospital [4] 0 0
St John of God Subiaco Hospital ( Site 1512) - Subiaco
Recruitment hospital [5] 0 0
Monash Health-Monash Medical Centre ( Site 1519) - Clayton
Recruitment postcode(s) [1] 0 0
2065 - St Leonards
Recruitment postcode(s) [2] 0 0
4101 - South Brisbane
Recruitment postcode(s) [3] 0 0
5042 - Bedford Park
Recruitment postcode(s) [4] 0 0
6008 - Subiaco
Recruitment postcode(s) [5] 0 0
3168 - Clayton
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alaska
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Connecticut
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Georgia
Country [7] 0 0
United States of America
State/province [7] 0 0
Michigan
Country [8] 0 0
United States of America
State/province [8] 0 0
Missouri
Country [9] 0 0
United States of America
State/province [9] 0 0
New Jersey
Country [10] 0 0
United States of America
State/province [10] 0 0
New York
Country [11] 0 0
United States of America
State/province [11] 0 0
Ohio
Country [12] 0 0
United States of America
State/province [12] 0 0
Oklahoma
Country [13] 0 0
United States of America
State/province [13] 0 0
South Carolina
Country [14] 0 0
United States of America
State/province [14] 0 0
Tennessee
Country [15] 0 0
United States of America
State/province [15] 0 0
Texas
Country [16] 0 0
United States of America
State/province [16] 0 0
Washington
Country [17] 0 0
Argentina
State/province [17] 0 0
Buenos Aires
Country [18] 0 0
Argentina
State/province [18] 0 0
La Rioja
Country [19] 0 0
Argentina
State/province [19] 0 0
Tucuman
Country [20] 0 0
Canada
State/province [20] 0 0
Alberta
Country [21] 0 0
Canada
State/province [21] 0 0
British Columbia
Country [22] 0 0
Canada
State/province [22] 0 0
Manitoba
Country [23] 0 0
Canada
State/province [23] 0 0
Nova Scotia
Country [24] 0 0
Canada
State/province [24] 0 0
Ontario
Country [25] 0 0
Canada
State/province [25] 0 0
Quebec
Country [26] 0 0
Chile
State/province [26] 0 0
Valparaiso
Country [27] 0 0
Chile
State/province [27] 0 0
Santiago
Country [28] 0 0
Chile
State/province [28] 0 0
Temuco
Country [29] 0 0
Colombia
State/province [29] 0 0
Cesar
Country [30] 0 0
Colombia
State/province [30] 0 0
Cundinamarca
Country [31] 0 0
Colombia
State/province [31] 0 0
Valle
Country [32] 0 0
Colombia
State/province [32] 0 0
Barranquilla
Country [33] 0 0
Colombia
State/province [33] 0 0
Monteria
Country [34] 0 0
Colombia
State/province [34] 0 0
Pasto
Country [35] 0 0
France
State/province [35] 0 0
Clermont Ferrand
Country [36] 0 0
France
State/province [36] 0 0
Marseille
Country [37] 0 0
France
State/province [37] 0 0
Paris
Country [38] 0 0
France
State/province [38] 0 0
Rennes
Country [39] 0 0
France
State/province [39] 0 0
Saint-Cloud
Country [40] 0 0
Germany
State/province [40] 0 0
Dresden
Country [41] 0 0
Germany
State/province [41] 0 0
Duesseldorf
Country [42] 0 0
Germany
State/province [42] 0 0
Essen
Country [43] 0 0
Germany
State/province [43] 0 0
Hamburg
Country [44] 0 0
Germany
State/province [44] 0 0
Hannover
Country [45] 0 0
Germany
State/province [45] 0 0
Kiel
Country [46] 0 0
Germany
State/province [46] 0 0
Muenchen
Country [47] 0 0
Germany
State/province [47] 0 0
Oldenburg
Country [48] 0 0
Germany
State/province [48] 0 0
Regensburg
Country [49] 0 0
Israel
State/province [49] 0 0
Beer-Sheva
Country [50] 0 0
Israel
State/province [50] 0 0
Haifa
Country [51] 0 0
Israel
State/province [51] 0 0
Jerusalem
Country [52] 0 0
Israel
State/province [52] 0 0
Petah Tikva
Country [53] 0 0
Israel
State/province [53] 0 0
Ramat Gan
Country [54] 0 0
Israel
State/province [54] 0 0
Tel Aviv
Country [55] 0 0
Italy
State/province [55] 0 0
Aviano
Country [56] 0 0
Italy
State/province [56] 0 0
Bolgna
Country [57] 0 0
Italy
State/province [57] 0 0
Milano
Country [58] 0 0
Italy
State/province [58] 0 0
Napoli
Country [59] 0 0
Italy
State/province [59] 0 0
Roma
Country [60] 0 0
Japan
State/province [60] 0 0
Chiba
Country [61] 0 0
Japan
State/province [61] 0 0
Ehime
Country [62] 0 0
Japan
State/province [62] 0 0
Fukuoka
Country [63] 0 0
Japan
State/province [63] 0 0
Hokkaido
Country [64] 0 0
Japan
State/province [64] 0 0
Hyogo
Country [65] 0 0
Japan
State/province [65] 0 0
Iwate
Country [66] 0 0
Japan
State/province [66] 0 0
Okinawa
Country [67] 0 0
Japan
State/province [67] 0 0
Saitama
Country [68] 0 0
Japan
State/province [68] 0 0
Shizuoka
Country [69] 0 0
Japan
State/province [69] 0 0
Tokyo
Country [70] 0 0
Korea, Republic of
State/province [70] 0 0
Daegu
Country [71] 0 0
Korea, Republic of
State/province [71] 0 0
Seoul
Country [72] 0 0
Mexico
State/province [72] 0 0
Yucatan
Country [73] 0 0
Mexico
State/province [73] 0 0
Chihuahua
Country [74] 0 0
Mexico
State/province [74] 0 0
Ciudad de Mexico
Country [75] 0 0
Mexico
State/province [75] 0 0
Mexico
Country [76] 0 0
Mexico
State/province [76] 0 0
San Pedro Garza Garcia
Country [77] 0 0
Mexico
State/province [77] 0 0
Veracruz
Country [78] 0 0
Peru
State/province [78] 0 0
La Libertad
Country [79] 0 0
Peru
State/province [79] 0 0
Arequipa
Country [80] 0 0
Peru
State/province [80] 0 0
Lima
Country [81] 0 0
Russian Federation
State/province [81] 0 0
Kazan
Country [82] 0 0
Russian Federation
State/province [82] 0 0
Moscow
Country [83] 0 0
Russian Federation
State/province [83] 0 0
Novosibirsk
Country [84] 0 0
Russian Federation
State/province [84] 0 0
Saint Petersburg
Country [85] 0 0
Russian Federation
State/province [85] 0 0
Saransk
Country [86] 0 0
Russian Federation
State/province [86] 0 0
St. Petersburg
Country [87] 0 0
Russian Federation
State/province [87] 0 0
Tomsk
Country [88] 0 0
Russian Federation
State/province [88] 0 0
Ufa
Country [89] 0 0
Spain
State/province [89] 0 0
Guipuzcoa
Country [90] 0 0
Spain
State/province [90] 0 0
Madrid
Country [91] 0 0
Spain
State/province [91] 0 0
Badalona
Country [92] 0 0
Spain
State/province [92] 0 0
Sevilla
Country [93] 0 0
Taiwan
State/province [93] 0 0
Kaohsiung
Country [94] 0 0
Taiwan
State/province [94] 0 0
Taichung
Country [95] 0 0
Taiwan
State/province [95] 0 0
Taipei
Country [96] 0 0
Taiwan
State/province [96] 0 0
Taoyuan
Country [97] 0 0
Turkey
State/province [97] 0 0
Adana
Country [98] 0 0
Turkey
State/province [98] 0 0
Ankara
Country [99] 0 0
Turkey
State/province [99] 0 0
Antalya
Country [100] 0 0
Turkey
State/province [100] 0 0
Istanbul
Country [101] 0 0
Turkey
State/province [101] 0 0
Izmir
Country [102] 0 0
Turkey
State/province [102] 0 0
Konya
Country [103] 0 0
Ukraine
State/province [103] 0 0
Dnipropetrovsk
Country [104] 0 0
Ukraine
State/province [104] 0 0
Ivano-Frankivsk
Country [105] 0 0
Ukraine
State/province [105] 0 0
Kharkiv
Country [106] 0 0
Ukraine
State/province [106] 0 0
Kyiv
Country [107] 0 0
Ukraine
State/province [107] 0 0
Odesa
Country [108] 0 0
Ukraine
State/province [108] 0 0
Zaporizhzhya

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Merck Sharp & Dohme LLC
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: http://engagezone.msd.com/ds_documentation.php


What supporting documents are/will be available?

Results publications and other study-related documents

TypeCitations or Other Details
Journal Monk BJ, Colombo N, Tewari KS, Dubot C, Caceres MV... [More Details]