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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
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Pennsylvania
Country [18] 0 0
United States of America
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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
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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
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Los Lagos
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Chile
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Region M. De Santiago
Country [39] 0 0
China
State/province [39] 0 0
Anhui
Country [40] 0 0
China
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Beijing
Country [41] 0 0
China
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Fujian
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China
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Gansu
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China
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Guangdong
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China
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Guangxi
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China
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Hainan
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China
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Henan
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China
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Hubei
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China
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Hunan
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China
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Jiangsu
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China
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Jiangxi
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China
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Jilin
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China
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Shandong
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China
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Shanghai
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China
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Sichuan
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China
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Tianjin
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China
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Yunnan
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China
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Zhejiang
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Colombia
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Antioquia
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Colombia
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Atlantico
Country [60] 0 0
Colombia
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Distrito Capital De Bogota
Country [61] 0 0
Colombia
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Risaralda
Country [62] 0 0
Colombia
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Valle Del Cauca
Country [63] 0 0
Denmark
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Nordjylland
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Finland
State/province [64] 0 0
Varsinais-Suomi
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France
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Bretagne
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France
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Calvados
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France
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Haute-Vienne
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France
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Hauts-de-Seine
Country [69] 0 0
France
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Ille-et-Vilaine
Country [70] 0 0
France
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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
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Germany
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Sachsen
Country [76] 0 0
Germany
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Berlin
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Germany
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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
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Chiba
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Japan
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Ehime
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Japan
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Fukuoka
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Japan
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Hokkaido
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Japan
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Iwate
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Japan
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Kanagawa
Country [98] 0 0
Japan
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Saitama
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Japan
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Shizuoka
Country [100] 0 0
Japan
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Tokyo
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Japan
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Osaka
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Korea, Republic of
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Seoul
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Mexico
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Baja California Sur
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Mexico
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Distrito Federal
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Mexico
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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
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Zuid-Holland
Country [109] 0 0
Netherlands
State/province [109] 0 0
Utrecht
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New Zealand
State/province [110] 0 0
Auckland
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Norway
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Troms
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Poland
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Mazowieckie
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Poland
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Podlaskie
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Poland
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Pomorskie
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Poland
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Slaskie
Country [116] 0 0
Poland
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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