Register a trial

Please note the ANZCTR will be unattended from Friday 20 December 2024 for the holidays. The Registry will re-open on Tuesday 7 January 2025. Submissions and updates will not be processed during that time.

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05116189




Registration number
NCT05116189
Ethics application status
Date submitted
28/10/2021
Date registered
10/11/2021

Titles & IDs
Public title
Pembrolizumab/Placebo Plus Paclitaxel With or Without Bevacizumab for Platinum-resistant Recurrent Ovarian Cancer (MK-3475-B96/KEYNOTE-B96/ENGOT-ov65)
Scientific title
A Phase 3, Randomized, Double-Blind Study of Pembrolizumab Versus Placebo in Combination With Paclitaxel With or Without Bevacizumab for the Treatment of Platinum-resistant Recurrent Ovarian Cancer (KEYNOTE-B96/ENGOT-ov65)
Secondary ID [1] 0 0
MK-3475-B96
Secondary ID [2] 0 0
3475-B96
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ovarian Cancer 0 0
Carcinoma, Ovarian Epithelial 0 0
Fallopian Tube Neoplasms 0 0
Condition category
Condition code
Cancer 0 0 0 0
Ovarian and primary peritoneal
Cancer 0 0 0 0
Womb (Uterine or endometrial cancer)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Pembrolizumab
Treatment: Drugs - Paclitaxel
Treatment: Drugs - Bevacizumab
Other interventions - Placebo for pembrolizumab
Treatment: Drugs - Docetaxel

Experimental: Pembrolizumab + paclitaxel ± bevacizumab - Participants receive pembrolizumab 400 mg via intravenous (IV) infusion for eighteen 6-week cycles (approximately 2 years) PLUS paclitaxel 80 mg/m\^2 via IV infusion on Days 1, 8, and 15 of each 3-week cycle until intolerance or disease progression. Participants who experience severe hypersensitivity reaction to paclitaxel or an AE requiring discontinuation of paclitaxel may receive docetaxel (75 mg/m\^2 every 3 weeks \[Q3W\]) after Sponsor consultation. Participants may also receive bevacizumab 10 mg/kg via IV infusion of each 2-week cycle until intolerance, disease progression, or at the Investigator's discretion.

Placebo comparator: Placebo + paclitaxel ± bevacizumab - Participants receive placebo via IV infusion for eighteen 6-week cycles (approximately 2 years) PLUS paclitaxel 80 mg/m\^2 via IV infusion on Days 1, 8, and 15 of each 3-week cycle until intolerance or disease progression. Participants who experience severe hypersensitivity reaction to paclitaxel or an AE requiring discontinuation of paclitaxel may receive docetaxel (75 mg/m\^2 every 3 weeks \[Q3W\]) after Sponsor consultation. Participants may also receive bevacizumab 10 mg/kg via IV infusion of each 2-week cycle until intolerance, disease progression, or at the Investigator's discretion.


Treatment: Other: Pembrolizumab
IV infusion

Treatment: Drugs: Paclitaxel
IV infusion

Treatment: Drugs: Bevacizumab
IV infusion

Other interventions: Placebo for pembrolizumab
IV infusion

Treatment: Drugs: Docetaxel
IV infusion
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Drugs
Intervention code [3] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) by Investigator
Timepoint [1] 0 0
Up to ~38 months
Secondary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
Up to ~64 months
Secondary outcome [2] 0 0
PFS per RECIST 1.1 by Blinded Independent Central Review (BICR)
Timepoint [2] 0 0
Up to ~38 months
Secondary outcome [3] 0 0
Number of Participants who Experience an Adverse Event (AE)
Timepoint [3] 0 0
Up to ~64 months
Secondary outcome [4] 0 0
Number of Participants who Discontinue Study Treatment due to an AE
Timepoint [4] 0 0
Up to ~64 months
Secondary outcome [5] 0 0
Change From Baseline in Global Health Status/Quality of Life (GHS/Qol) Score (Items 29 and 30) Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)
Timepoint [5] 0 0
Baseline and up to ~64 months
Secondary outcome [6] 0 0
Time to Deterioration (TTD) in the GHS/Qol Score (Items 29 and 30) Using the EORTC QLQ-C30
Timepoint [6] 0 0
Up to ~64 months
Secondary outcome [7] 0 0
Change From Baseline in the Abdominal and Gastrointestinal (GI) Symptoms Score (Items 31 to 36) Using the EORTC Quality of Life Questionnaire-Ovarian Cancer (QLQ-OV28) Abdominal/GI Symptom Scale
Timepoint [7] 0 0
Baseline and up to ~64 months
Secondary outcome [8] 0 0
TTD in the Abdominal and GI Symptoms Score (Items 31 to 36) Using the EORTC QLQ-OV28 Abdominal/GI Symptom Scale
Timepoint [8] 0 0
Up to ~64 months

Eligibility
Key inclusion criteria
* Has histologically confirmed epithelial ovarian, fallopian tube, or primary peritoneal carcinoma.
* Has received 1 or 2 prior lines of systemic therapy for ovarian cancer (OC), including at least 1 prior platinum-based therapy. Participants may have received a prior poly (ADP-ribose) polymerase inhibitor (PARPi), anti-PD-1/anti-PD-L1 therapy, bevacizumab, or hormonal therapy; these will not be considered a separate line of therapy. Any chemotherapy regimen change due to toxicity in the absence of disease progression will be considered part of the same line of therapy.
* Has provided documented informed consent for the study.
* Has radiographic evidence of disease progression within 6 months (180 days) after the last dose of platinum-based chemotherapy for OC (i.e., platinum-resistant disease).
* Is a candidate for paclitaxel chemotherapy (and bevacizumab, if using).
* Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 assessed within 3 days before randomization.
* For a female participant, she is not pregnant or breastfeeding, and at least one of the following conditions applies: Is not a woman of childbearing potential (WOCBP) OR Is a WOCBP and uses a contraceptive method that is highly effective (with a failure rate of <1% per year).
* Has radiographically evaluable disease, either measurable or nonmeasurable per RECIST 1.1, as assessed by the local site investigator.
* Archival tumor tissue sample or newly obtained core or incisional/excisional biopsy of a tumor lesion not previously irradiated has been provided.
* Have adequate organ function.
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
* Has nonepithelial cancers, borderline tumors, mucinous, seromucinous that is predominantly mucinous, malignant Brenner's tumor and undifferentiated carcinoma.
* Has primary platinum-refractory disease, defined as disease that has progressed per radiographic imaging while receiving or within 28 days of the last dose of first-line platinum-based therapy.
* Has prior disease progression on weekly paclitaxel alone.
* Has received >2 prior lines of systemic therapy for OC.
* Has received prior systemic anticancer therapy including investigational agents or maintenance therapy (including bevacizumab maintenance therapy), within 4 weeks before randomization.
* Has received prior radiation therapy within 2 weeks of start of study intervention.
* Has not recovered adequately from surgery and/or any complications from the surgery.
* Has received colony-stimulating factors (e.g., granulocyte colony-stimulating factor [G-CSF], granulocyte-macrophage colony-stimulating factor,[GM-CSF] or recombinant erythropoietin) within 4 weeks before randomization.
* Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention.
* Has received investigational agent or has used an investigational device within 4 weeks prior to study intervention.
* Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy.
* Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
* Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
* Has severe hypersensitivity (=Grade 3) to pembrolizumab, paclitaxel, or bevacizumab (if using) and/or any of their excipients.
* Has an active autoimmune disease that has required systemic treatment in the past 2 years.
* Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
* 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, laboratory abnormality, or other circumstance that might confound the results of the 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.
* Participant, in the judgement of the investigator, is unlikely to comply with the study procedures, restrictions, and requirements of the study.
* Has had an allogenic tissue/solid organ transplant.

For bevacizumab treatment

* Has uncontrolled hypertension.
* Has current, clinically relevant bowel obstruction including related to underlying epithelial OC, abdominal fistula or gastrointestinal perforation, intra-abdominal abscess, or evidence of rectosigmoid involvement by pelvic exam.
* Has a history of thrombotic disorders, hemorrhage, hemoptysis, or active gastrointestinal bleeding within 6 months before randomization.

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
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
13/12/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/08/2027
Actual
Sample size
Target
616
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
Westmead Hospital-Department of Gynaecological Oncology ( Site 0201) - Westmead
Recruitment hospital [2] 0 0
Gallipoli Medical Research Foundation-GMRF CTU ( Site 0202) - Brisbane
Recruitment hospital [3] 0 0
Epworth Freemasons ( Site 0204) - Melbourne
Recruitment hospital [4] 0 0
St. John of God Subiaco Hospital ( Site 0203) - Subiaco
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment postcode(s) [2] 0 0
4120 - Brisbane
Recruitment postcode(s) [3] 0 0
3002 - Melbourne
Recruitment postcode(s) [4] 0 0
6008 - Subiaco
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Indiana
Country [8] 0 0
United States of America
State/province [8] 0 0
Kentucky
Country [9] 0 0
United States of America
State/province [9] 0 0
Louisiana
Country [10] 0 0
United States of America
State/province [10] 0 0
Maryland
Country [11] 0 0
United States of America
State/province [11] 0 0
Massachusetts
Country [12] 0 0
United States of America
State/province [12] 0 0
New Jersey
Country [13] 0 0
United States of America
State/province [13] 0 0
New York
Country [14] 0 0
United States of America
State/province [14] 0 0
North Carolina
Country [15] 0 0
United States of America
State/province [15] 0 0
Ohio
Country [16] 0 0
United States of America
State/province [16] 0 0
Oregon
Country [17] 0 0
United States of America
State/province [17] 0 0
Pennsylvania
Country [18] 0 0
United States of America
State/province [18] 0 0
South Dakota
Country [19] 0 0
United States of America
State/province [19] 0 0
Tennessee
Country [20] 0 0
United States of America
State/province [20] 0 0
Texas
Country [21] 0 0
United States of America
State/province [21] 0 0
Virginia
Country [22] 0 0
Belgium
State/province [22] 0 0
Bruxelles-Capitale, Region De
Country [23] 0 0
Belgium
State/province [23] 0 0
Oost-Vlaanderen
Country [24] 0 0
Belgium
State/province [24] 0 0
Vlaams-Brabant
Country [25] 0 0
Belgium
State/province [25] 0 0
West-Vlaanderen
Country [26] 0 0
Brazil
State/province [26] 0 0
Goias
Country [27] 0 0
Brazil
State/province [27] 0 0
Rio Grande Do Norte
Country [28] 0 0
Brazil
State/province [28] 0 0
Santa Catarina
Country [29] 0 0
Brazil
State/province [29] 0 0
Sao Paulo
Country [30] 0 0
Brazil
State/province [30] 0 0
Rio de Janeiro
Country [31] 0 0
Canada
State/province [31] 0 0
Alberta
Country [32] 0 0
Canada
State/province [32] 0 0
British Columbia
Country [33] 0 0
Canada
State/province [33] 0 0
Ontario
Country [34] 0 0
Canada
State/province [34] 0 0
Quebec
Country [35] 0 0
Canada
State/province [35] 0 0
Saskatchewan
Country [36] 0 0
Chile
State/province [36] 0 0
Araucania
Country [37] 0 0
Chile
State/province [37] 0 0
Los Lagos
Country [38] 0 0
Chile
State/province [38] 0 0
Region M. De Santiago
Country [39] 0 0
China
State/province [39] 0 0
Anhui
Country [40] 0 0
China
State/province [40] 0 0
Beijing
Country [41] 0 0
China
State/province [41] 0 0
Fujian
Country [42] 0 0
China
State/province [42] 0 0
Gansu
Country [43] 0 0
China
State/province [43] 0 0
Guangdong
Country [44] 0 0
China
State/province [44] 0 0
Guangxi
Country [45] 0 0
China
State/province [45] 0 0
Hainan
Country [46] 0 0
China
State/province [46] 0 0
Henan
Country [47] 0 0
China
State/province [47] 0 0
Hubei
Country [48] 0 0
China
State/province [48] 0 0
Hunan
Country [49] 0 0
China
State/province [49] 0 0
Jiangsu
Country [50] 0 0
China
State/province [50] 0 0
Jiangxi
Country [51] 0 0
China
State/province [51] 0 0
Jilin
Country [52] 0 0
China
State/province [52] 0 0
Shandong
Country [53] 0 0
China
State/province [53] 0 0
Shanghai
Country [54] 0 0
China
State/province [54] 0 0
Sichuan
Country [55] 0 0
China
State/province [55] 0 0
Tianjin
Country [56] 0 0
China
State/province [56] 0 0
Yunnan
Country [57] 0 0
China
State/province [57] 0 0
Zhejiang
Country [58] 0 0
Colombia
State/province [58] 0 0
Antioquia
Country [59] 0 0
Colombia
State/province [59] 0 0
Atlantico
Country [60] 0 0
Colombia
State/province [60] 0 0
Distrito Capital De Bogota
Country [61] 0 0
Colombia
State/province [61] 0 0
Risaralda
Country [62] 0 0
Colombia
State/province [62] 0 0
Valle Del Cauca
Country [63] 0 0
Denmark
State/province [63] 0 0
Nordjylland
Country [64] 0 0
Finland
State/province [64] 0 0
Varsinais-Suomi
Country [65] 0 0
France
State/province [65] 0 0
Bretagne
Country [66] 0 0
France
State/province [66] 0 0
Calvados
Country [67] 0 0
France
State/province [67] 0 0
Haute-Vienne
Country [68] 0 0
France
State/province [68] 0 0
Hauts-de-Seine
Country [69] 0 0
France
State/province [69] 0 0
Ille-et-Vilaine
Country [70] 0 0
France
State/province [70] 0 0
Languedoc-Roussillon
Country [71] 0 0
France
State/province [71] 0 0
Loire-Atlantique
Country [72] 0 0
Germany
State/province [72] 0 0
Bayern
Country [73] 0 0
Germany
State/province [73] 0 0
Nordrhein-Westfalen
Country [74] 0 0
Germany
State/province [74] 0 0
Saarland
Country [75] 0 0
Germany
State/province [75] 0 0
Sachsen
Country [76] 0 0
Germany
State/province [76] 0 0
Berlin
Country [77] 0 0
Germany
State/province [77] 0 0
Hamburg
Country [78] 0 0
Ireland
State/province [78] 0 0
Dublin
Country [79] 0 0
Israel
State/province [79] 0 0
Afula
Country [80] 0 0
Israel
State/province [80] 0 0
Be'er Sheva
Country [81] 0 0
Israel
State/province [81] 0 0
Haifa
Country [82] 0 0
Israel
State/province [82] 0 0
Jerusalem
Country [83] 0 0
Israel
State/province [83] 0 0
Petah-Tikva
Country [84] 0 0
Israel
State/province [84] 0 0
Ramat Gan
Country [85] 0 0
Israel
State/province [85] 0 0
Tel Aviv
Country [86] 0 0
Italy
State/province [86] 0 0
Emilia-Romagna
Country [87] 0 0
Italy
State/province [87] 0 0
Lombardia
Country [88] 0 0
Italy
State/province [88] 0 0
Milano
Country [89] 0 0
Italy
State/province [89] 0 0
Piemonte
Country [90] 0 0
Italy
State/province [90] 0 0
Brescia
Country [91] 0 0
Japan
State/province [91] 0 0
Aichi
Country [92] 0 0
Japan
State/province [92] 0 0
Chiba
Country [93] 0 0
Japan
State/province [93] 0 0
Ehime
Country [94] 0 0
Japan
State/province [94] 0 0
Fukuoka
Country [95] 0 0
Japan
State/province [95] 0 0
Hokkaido
Country [96] 0 0
Japan
State/province [96] 0 0
Iwate
Country [97] 0 0
Japan
State/province [97] 0 0
Kanagawa
Country [98] 0 0
Japan
State/province [98] 0 0
Saitama
Country [99] 0 0
Japan
State/province [99] 0 0
Shizuoka
Country [100] 0 0
Japan
State/province [100] 0 0
Tokyo
Country [101] 0 0
Japan
State/province [101] 0 0
Osaka
Country [102] 0 0
Korea, Republic of
State/province [102] 0 0
Seoul
Country [103] 0 0
Mexico
State/province [103] 0 0
Baja California Sur
Country [104] 0 0
Mexico
State/province [104] 0 0
Distrito Federal
Country [105] 0 0
Mexico
State/province [105] 0 0
Nuevo Leon
Country [106] 0 0
Mexico
State/province [106] 0 0
Oaxaca
Country [107] 0 0
Netherlands
State/province [107] 0 0
Gelderland
Country [108] 0 0
Netherlands
State/province [108] 0 0
Zuid-Holland
Country [109] 0 0
Netherlands
State/province [109] 0 0
Utrecht
Country [110] 0 0
New Zealand
State/province [110] 0 0
Auckland
Country [111] 0 0
Norway
State/province [111] 0 0
Troms
Country [112] 0 0
Poland
State/province [112] 0 0
Mazowieckie
Country [113] 0 0
Poland
State/province [113] 0 0
Podlaskie
Country [114] 0 0
Poland
State/province [114] 0 0
Pomorskie
Country [115] 0 0
Poland
State/province [115] 0 0
Slaskie
Country [116] 0 0
Poland
State/province [116] 0 0
Swietokrzyskie
Country [117] 0 0
Poland
State/province [117] 0 0
Wielkopolskie
Country [118] 0 0
Russian Federation
State/province [118] 0 0
Chelyabinskaya Oblast
Country [119] 0 0
Russian Federation
State/province [119] 0 0
Mordoviya, Respublika
Country [120] 0 0
Russian Federation
State/province [120] 0 0
Moskovskaya Oblast
Country [121] 0 0
Russian Federation
State/province [121] 0 0
Moskva
Country [122] 0 0
Russian Federation
State/province [122] 0 0
Sverdlovskaya Oblast
Country [123] 0 0
Turkey
State/province [123] 0 0
Adana
Country [124] 0 0
Turkey
State/province [124] 0 0
Istanbul
Country [125] 0 0
Turkey
State/province [125] 0 0
Izmir
Country [126] 0 0
Turkey
State/province [126] 0 0
Ankara
Country [127] 0 0
United Kingdom
State/province [127] 0 0
Brighton And Hove
Country [128] 0 0
United Kingdom
State/province [128] 0 0
Cambridgeshire
Country [129] 0 0
United Kingdom
State/province [129] 0 0
Cornwall
Country [130] 0 0
United Kingdom
State/province [130] 0 0
Cumbria
Country [131] 0 0
United Kingdom
State/province [131] 0 0
Dundee City
Country [132] 0 0
United Kingdom
State/province [132] 0 0
England
Country [133] 0 0
United Kingdom
State/province [133] 0 0
London, City Of
Country [134] 0 0
United Kingdom
State/province [134] 0 0
Cardiff

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?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT05116189