Ovarian Cancer Clinical Trial
Study of Chemotherapy With Pembrolizumab (MK-3475) Followed by Maintenance With Olaparib (MK-7339) for the First-Line Treatment of Women With BRCA Non-mutated Advanced Epithelial Ovarian Cancer (EOC) (MK-7339-001/KEYLYNK-001/ENGOT-ov43/GOG-3036)
Summary
The purpose of this study is to assess the efficacy and safety of treatment with carboplatin/paclitaxel* PLUS pembrolizumab (MK-3475) and maintenance olaparib (MK-7339) in women with epithelial ovarian cancer (EOC), fallopian tube cancer, or primary peritoneal cancer.
The primary study hypotheses are that the combination of pembrolizumab plus carboplatin/paclitaxel* followed by continued pembrolizumab and maintenance olaparib is superior to carboplatin/paclitaxel alone with respect to Progression Free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in participants with programmed death-ligand 1 (PD-L1)-positive tumors (Combined Positive Score [CPS]≥10) and in all participants, and that the combination of pembrolizumab plus carboplatin/paclitaxel followed by continued pembrolizumab is superior to carboplatin/paclitaxel alone with respect to PFS per RECIST 1.1 in participants with PD-L1-positive tumors (CPS≥10) and in all participants.
Full Description
Following a lead-in period during which all participants receive a single 3-week cycle of carboplatin/paclitaxel*, participants will be randomly assigned in to one of three treatment arms:
Pembrolizumab + Olaparib,
Pembrolizumab + Placebo for Olaparib
Placebo for Pembrolizumab + Placebo for Olaparib
At Investigator's discretion and prior to participant randomization, one of the following carboplatin/paclitaxel regimens is to be selected:
up to 5 cycles of carboplatin Area Under the Curve (AUC)5 or AUC6 AND paclitaxel 175 mg/m^2 on Day 1 of each 3-week cycle
up to 5 cycles of carboplatin AUC5 or AUC6 on Day 1 of each 3-week cycle AND paclitaxel 80 mg/m^2 on Days 1, 8 and 15 of each 3-week cycle; or
up to 5 cycles of carboplatin AUC2 or AUC2.7 AND paclitaxel 60 mg/m^2 on Days 1, 8 and 15 of each 3-week cycle.
Docetaxel may be considered for participants who experience either a severe hypersensitivity reaction to paclitaxel or an AE requiring discontinuation of paclitaxel only after consultation with the Sponsor. The recommended dose as determined by the Scottish Gynaecological Cancer Trials Group is Docetaxel 75 mg/m^2 Q3W plus carboplatin AUC 5 Q3W.
Eligibility Criteria
Inclusion Criteria:
Has histologically confirmed International Federation of Gynecology and Obstetrics (FIGO) Stage III or Stage IV EOC (high-grade predominantly serous, endometrioid (any grade), carcinosarcoma, mixed mullerian with high-grade serous component, clear cell, or low-grade serous OC), primary peritoneal cancer, or fallopian tube cancer
Has just completed primary debulking surgery or is eligible for primary debulking surgery or is a potential candidate for interval debulking surgery
Is a candidate for carboplatin and paclitaxel chemotherapy, to be administered in the adjuvant or neoadjuvant setting
Candidates for neoadjuvant chemotherapy, has a cancer antigen 125 (CA-125) (kilounits/L):carcinoembryonic antigen (CEA; ng/mL) ratio greater than or equal to 25
Is able to provide a newly obtained core or excisional biopsy of a tumor lesion for prospective testing of BRCA1/2 and Programmed Cell Death-Ligand 1 (PD-L1) tumor markers status prior to randomization
Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, as assessed within 7 days prior to initiating chemotherapy in the lead-in period and within 3 days prior to Day 1 of Cycle 1
Female participants are not pregnant, not breastfeeding, and at least 1 of the following conditions applies: a.) Not a woman of childbearing potential (WOCBP) OR b.) Is a WOCBP and using a contraceptive method that is highly effective, with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle, during the Treatment Period and for at least 120 days following the last dose of pembrolizumab (or pembrolizumab placebo) and bevacizumab (if administered), at least 180 days following the last dose of olaparib (or olaparib placebo), and at least 210 days following the last dose of chemotherapy 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. The investigator should evaluate the potential for contraceptive method failure in relationship to the first dose of study treatment. A WOCBP must have a negative highly sensitive pregnancy test within either 24 hours (urine) or 72 hours (serum) before the first dose of study treatment. If a urine test cannot be confirmed as negative, a serum pregnancy test is required. The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy. Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
Has adequate organ function
Exclusion Criteria:
Has mucinous, germ cell, or borderline tumor of the ovary
Has a known or suspected deleterious mutation (germline or somatic) in either BRCA1 or BRCA2
Has a history of non-infectious pneumonitis that required treatment with steroids or currently has pneumonitis
Has either myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or has features suggestive of MDS/AML
Has a known additional malignancy that is progressing or has required active treatment in the last 3 years Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. ductal carcinoma in situ, cervical carcinoma in situ) that has undergone potentially curative therapy are not excluded.
Has ongoing Grade 3 or Grade 4 toxicity, excluding alopecia, following chemotherapy administered during the lead-in period
Has known active central nervous system metastases and/or carcinomatous meningitis. Participants with brain metastases may participate provided they were previously treated (except with chemotherapy) and are radiologically stable, clinically stable, and no steroids were used for the management of symptoms related to brain metastases within 14 days prior to randomization. Stable brain metastases should be established prior to the first dose of study medication lead-in chemotherapy
Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (dosing >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 the past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs) Note: 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 known history of active tuberculosis (TB; Bacillus Tuberculosis)
Has an active infection requiring systemic therapy
Has received colony-stimulating factors (eg, granulocyte colony stimulating factor [G-CSF], granulocyte macrophage colony-stimulating factor [GM-CSF] or recombinant erythropoietin) within 4 weeks prior to receiving chemotherapy during the lead-in period
Is considered to be of poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection
Has had surgery to treat borderline tumors, early stage EOC, or early stage fallopian tube cancer <6 months prior to screening
Has a known history of human immunodeficiency virus (HIV) infection
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. Testing for hepatitis B or hepatitis C is required at screening only if mandated by local health authority. Note: Participants with a history of hepatitis B but who are HBsAg negative are eligible for the study
Is either unable to swallow orally administered medication or has a gastrointestinal (GI) disorder affecting absorption (e.g. gastrectomy, partial bowel obstruction, malabsorption)
Has uncontrolled hypertension
Has current, clinically relevant bowel obstruction (including sub-occlusive disease), abdominal fistula or GI perforation, related to underlying EOC (for participants receiving bevacizumab)
Has a history of hemorrhage, hemoptysis or active GI bleeding within 6 months prior to randomization (for participants receiving bevacizumab)
Is a WOCBP who has a positive urine pregnancy test within 72 hours before the first dose of chemotherapy in the lead-in period and within 72 hours prior to Day 1 of Cycle 1, is pregnant or breastfeeding, or is expecting to conceive children within the projected duration of the study, starting with screening through 120 days following the last dose of pembrolizumab (or pembrolizumab placebo) and bevacizumab (if administered), at least 180 days following the last dose of olaparib (or olaparib placebo), and at least 210 days following the last dose of chemotherapy
Has received prior treatment for any stage of OC, including radiation or systemic anti-cancer therapy (e.g. chemotherapy, hormonal therapy, immunotherapy, investigational therapy)
Has received prior therapy with an anti-Programmed Cell Death-1 (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 antigen-4 [CTLA-4], OX 40, CD137)
Has received prior therapy with either olaparib or any other poly(adenosine-ribose) polymerase (PARP) inhibitor
Has intraperitoneal chemotherapy planned or has been administered as first-line therapy
Has received a live vaccine within 30 days prior to the first dose of study treatment on Day 1 of Cycle 1
Has severe hypersensitivity (≥Grade 3) to pembrolizumab, olaparib, carboplatin, paclitaxel or bevacizumab (if using) and/or any of their excipients
Is currently receiving either strong (e.g. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate (eg, ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil) inhibitors of cytochrome P450 (CYP)3A4 that cannot be discontinued for the duration of the study
Is currently receiving either strong (e.g. phenobarbital, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine, and St John's Wort) or moderate (e.g. bosentan, efavirenz, modafinil) inducers of CYP3A4 that cannot be discontinued for the duration of the study
Is currently participating or has participated in a study of an investigational agent or has used an investigational device within 4 weeks (28 days) of starting chemotherapy in the Lead-in Period
Has resting electrocardiogram (ECG) indicating uncontrolled, potentially reversible cardiac conditions or participant has congenital long QT syndrome
Has had an allogenic tissue/solid organ transplant, has received previous allogenic bone-marrow transplant, or has received double umbilical cord transplantation
Either has had major surgery within 3 weeks of randomization or has not recovered from any effects of any major surgery
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There are 224 Locations for this study
Birmingham Alabama, 35233, United States
Tucson Arizona, 85719, United States
Burbank California, 91505, United States
Oakland California, 94611, United States
Roseville California, 95661, United States
Sacramento California, 95814, United States
San Francisco California, 94115, United States
Santa Clara California, 95051, United States
Vallejo California, 94589, United States
Walnut Creek California, 94596, United States
New Haven Connecticut, 06511, United States
Sarasota Florida, 34239, United States
Atlanta Georgia, 30322, United States
Gainesville Georgia, 30501, United States
Savannah Georgia, 31404, United States
Chicago Illinois, 60612, United States
Chicago Illinois, 60637, United States
Hinsdale Illinois, 60521, United States
Indianapolis Indiana, 46260, United States
Iowa City Iowa, 52242, United States
Lexington Kentucky, 40536, United States
Baltimore Maryland, 21237, United States
Jackson Mississippi, 39216, United States
Saint Louis Missouri, 63110, United States
Omaha Nebraska, 68114, United States
Lebanon New Hampshire, 03756, United States
Camden New Jersey, 08103, United States
Teaneck New Jersey, 07666, United States
Lake Success New York, 11042, United States
Fargo North Dakota, 58122, United States
Centerville Ohio, 45459, United States
Cincinnati Ohio, 45242, United States
Columbus Ohio, 43214, United States
Hilliard Ohio, 43026, United States
Providence Rhode Island, 02905, United States
Sioux Falls South Dakota, 57104, United States
Bedford Texas, 76022, United States
Dallas Texas, 75231, United States
Dallas Texas, 75235, United States
Dallas Texas, 75390, United States
Tyler Texas, 75702, United States
Gainesville Virginia, 20155, United States
Milwaukee Wisconsin, 53226, United States
Kogarah New South Wales, 2217, Australia
Cairns Queensland, 4870, Australia
Ballarat Victoria, 3350, Australia
Clayton Victoria, 3168, Australia
St Albans Victoria, 3021, Australia
Bonheiden Antwerpen, 1932, Belgium
Leuven Antwerpen, 3000, Belgium
Brussels Bruxelles-Capitale, Region De, 1200, Belgium
Charleroi Hainaut, 6000, Belgium
Liège Liege, 4000, Belgium
Hasselt Limburg, 3500, Belgium
Libramont Luxembourg, 6800, Belgium
Gent Oost-Vlaanderen, 9000, Belgium
Gent Oost-Vlaanderen, 9000, Belgium
Fortaleza Ceara, 60430, Brazil
Goiania Goias, 74605, Brazil
Curitiba Parana, 82520, Brazil
Ijui Rio Grande Do Sul, 98700, Brazil
Lajeado Rio Grande Do Sul, 95900, Brazil
Porto Alegre Rio Grande Do Sul, 91350, Brazil
Rio de Janeiro , 20220, Brazil
Sao Paulo , 01246, Brazil
Sao Paulo , 01317, Brazil
Sao Paulo , 01321, Brazil
Calgary Alberta, T2N 4, Canada
Kingston Ontario, K7L 2, Canada
Mississauga Ontario, L5M 2, Canada
Toronto Ontario, M5G 2, Canada
Chicoutimi Quebec, G7H 5, Canada
Montreal Quebec, H1T 2, Canada
Montreal Quebec, H2X 0, Canada
Montreal Quebec, H4A 3, Canada
Temuco Araucania, 47800, Chile
Temuco Araucania, 48102, Chile
Santiago Region M. De Santiago, 75009, Chile
Santiago Region M. De Santiago, 75100, Chile
Santiago Region M. De Santiago, 76303, Chile
Santiago Region M. De Santiago, 83300, Chile
Vina del Mar Valparaiso, 25205, Chile
Antofagasta , 12400, Chile
Barranquilla Atlantico, 08000, Colombia
Valledupar Cesar, 20000, Colombia
Monteria Cordoba, 23000, Colombia
Bogota Distrito Capital De Bogota, 11032, Colombia
Bogota Distrito Capital De Bogota, 11132, Colombia
Cali Valle Del Cauca, 76004, Colombia
Cali Valle Del Cauca, 76004, Colombia
Brno Brno-mesto, 602 0, Czechia
Ostrava-Poruba Moravskoslezsky Kraj, 708 5, Czechia
Praha Praha, Hlavni Mesto, 120 0, Czechia
Praha Praha, Hlavni Mesto, 180 8, Czechia
Olomouc , 779 0, Czechia
Lyon Auvergne, 69008, France
Strasbourg Bas-Rhin, 67065, France
Marseille Bouches-du-Rhone, 13005, France
Brest Bretagne, 29200, France
Nimes Gard, 30029, France
Saint-Priest-en-Jarez Loire, 42270, France
Nancy Meurthe-et-Moselle, 54100, France
Villejuif Val-de-Marne, 94800, France
Paris , 75020, France
Stuttgart Baden-Wurttemberg, 70199, Germany
Muenchen Bayern, 72074, Germany
Aachen Nordrhein-Westfalen, 52074, Germany
Bonn Nordrhein-Westfalen, 53111, Germany
Dortmund Nordrhein-Westfalen, 44137, Germany
Duesseldorf Nordrhein-Westfalen, 40225, Germany
Krefeld Nordrhein-Westfalen, 47805, Germany
Muenster Nordrhein-Westfalen, 48149, Germany
Saarbruecken Saarland, 66113, Germany
Chemnitz Sachsen, 09116, Germany
Kiel Schleswig-Holstein, 24116, Germany
Berlin , 13353, Germany
Pecs Baranya, 7624, Hungary
Miskolc Borsod-Abauj-Zemplen, 1051, Hungary
Budapest , 1122, Hungary
Budapest , 1145, Hungary
Debrecen , 4032, Hungary
Beer-Sheva , 84101, Israel
Hadera , 38101, Israel
Haifa , 34362, Israel
Haifa , 35254, Israel
Holon , 58220, Israel
Jerusalem , 91031, Israel
Petah Tikva , 49414, Israel
Ramat Gan , 52620, Israel
Tel Aviv , 64239, Israel
Bari Abruzzo, 70124, Italy
Milano Lombardia, 20141, Italy
Torino Piemonte, 10126, Italy
Padova Veneto, 35128, Italy
Benevento , 82100, Italy
Catania , 95126, Italy
Lecco , 23900, Italy
Milano , 20133, Italy
Napoli , 80131, Italy
Roma , 00161, Italy
Roma , 00168, Italy
Trento , 38122, Italy
Udine , 33100, Italy
Kashiwa Chiba, 277-8, Japan
Matsuyama Ehime, 791-0, Japan
Toon Ehime, 791-0, Japan
Ota Gunma, 373-8, Japan
Sapporo Hokkaido, 060-8, Japan
Shiwa-gun Iwate, 028-3, Japan
Kawasaki Kanagawa, 216-8, Japan
Nakagami-gun Okinawa, 903-0, Japan
Hidaka Saitama, 350-1, Japan
Kitaadachi-gun Saitama, 362-0, Japan
Tokorozawa Saitama, 359-8, Japan
Mitaka Tokyo, 181-8, Japan
Kagoshima , 890-8, Japan
Niigata , 951-8, Japan
Osaka , 541-8, Japan
Tokyo , 104-0, Japan
Seongnam-si Kyonggi-do, 13620, Korea, Republic of
Seoul , 03080, Korea, Republic of
Seoul , 03722, Korea, Republic of
Seoul , 05505, Korea, Republic of
Seoul , 06351, Korea, Republic of
Warszawa Mazowieckie, 02-78, Poland
Bialystok Podlaskie, 15-02, Poland
Gdynia Pomorskie, 81-51, Poland
Gliwice Slaskie, 44-10, Poland
Kielce Swietokrzyskie, 25-73, Poland
Poznan Wielkopolskie, 61-84, Poland
Arkhangelsk Arkhangel Skaya Oblast, 16304, Russian Federation
Ufa Baskortostan, Respublika, 45005, Russian Federation
Obninsk Kaluzskaja Oblast, 24903, Russian Federation
Moscow Moskva, 11547, Russian Federation
Moscow Moskva, 11568, Russian Federation
Moscow Moskva, 12536, Russian Federation
Saint Petersburg Sankt-Peterburg, 19825, Russian Federation
Saint-Petersburg Sankt-Peterburg, 19775, Russian Federation
Kazan Tatarstan, Respublika, 42002, Russian Federation
Port Elizabeth Eastern Cape, 6045, South Africa
Cape Town Gauteng, 7925, South Africa
Johannesburg Gauteng, 2193, South Africa
Pretoria Gauteng, 0002, South Africa
Pretoria Gauteng, 0031, South Africa
Pretoria Gauteng, 0081, South Africa
Pretoria Gauteng, 0181, South Africa
Sandton Gauteng, 2196, South Africa
Durban Kwazulu-Natal, 4091, South Africa
Cape Town Western Cape, 7700, South Africa
George Western Cape, 6530, South Africa
Kraaifontein Western Cape, 7570, South Africa
Hospitalet de Llobregat Barcelona, 08909, Spain
Manresa Barcelona, 08243, Spain
Terrassa Barcelona, 08227, Spain
Donostia Gipuzkoa, 20014, Spain
A Coruna La Coruna, 15006, Spain
Valencia Valenciana, Comunitat, 46009, Spain
Valencia Valenciana, Comunitat, 46014, Spain
Caceres , 10003, Spain
Lugo , 27003, Spain
Madrid , 28027, Spain
Sevilla , 41013, Spain
Changhua , 50006, Taiwan
Taichung , 40447, Taiwan
Taichung , 40705, Taiwan
Tainan , 704, Taiwan
Taipei , 10002, Taiwan
Taipei , 10449, Taiwan
Taipei , 11217, Taiwan
Taoyuan , 333, Taiwan
Kucukcekmece Istanbul, 34303, Turkey
Ankara , 06050, Turkey
Ankara , 06590, Turkey
Antalya , 07070, Turkey
Bursa , 16059, Turkey
Istanbul , 34093, Turkey
Istanbul , 34147, Turkey
Istanbul , 34214, Turkey
Sakarya , 54290, Turkey
Ivano-Frankivsk Ivano-Frankivska Oblast, 76018, Ukraine
Kharkiv Kharkivska Oblast, 61024, Ukraine
Khmelnytskyi Khmelnytska Oblast, 29009, Ukraine
Lviv Lvivska Oblast, 79031, Ukraine
Odesa Odeska Oblast, 65055, Ukraine
Sumy Sumska Oblast, 40022, Ukraine
Uzhgorod Zakarpatska Oblast, 88000, Ukraine
Kyiv , 03115, Ukraine
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