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Trial record 39 of 638 for:    Russian Federation | Chile

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)

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ClinicalTrials.gov Identifier: NCT03740165
Recruitment Status : Recruiting
First Posted : November 14, 2018
Last Update Posted : July 18, 2019
Sponsor:
Collaborator:
European Network for Gynaecological Oncological Trial Groups
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Brief 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) and/or Overall Survival (OS), 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 and/or OS.


Condition or disease Intervention/treatment Phase
Ovarian Cancer Fallopian Tube Cancer Peritoneal Neoplasms Biological: Pembrolizumab Drug: Placebo for pembrolizumab Drug: Carboplatin Drug: Paclitaxel Drug: Olaparib Drug: Placebo for olaparib Biological: Bevacizumab Phase 3

Detailed 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, or
  • 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:

  1. 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
  2. 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
  3. 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1086 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized Phase 3, Double-Blind Study of Chemotherapy With or Without Pembrolizumab Followed by Maintenance With Olaparib or Placebo for the First-Line Treatment of BRCA Non-mutated Advanced Epithelial Ovarian Cancer (EOC) (KEYLYNK-001/ENGOT-ov43)
Actual Study Start Date : December 18, 2018
Estimated Primary Completion Date : August 8, 2025
Estimated Study Completion Date : August 8, 2025


Arm Intervention/treatment
Experimental: Pembrolizumab+Olaparib
Participants receive carboplatin/paclitaxel via intravenous (IV) infusion for five 3-week cycles PLUS pembrolizumab 200 mg via IV infusion on Day 1 of each 3-week cycle for up to 35 cycles PLUS olaparib 300 mg via oral tablet twice each day (BID), starting with Cycle 7. Participants may also receive bevacizumab via IV infusion on Day 1 of each 3-week cycle.
Biological: Pembrolizumab
IV infusion
Other Names:
  • MK-3475
  • KEYTRUDA®

Drug: Carboplatin
IV infusion
Other Name: PARAPLATIN®

Drug: Paclitaxel
IV infusion
Other Name: TAXOL®

Drug: Olaparib
Oral tablet
Other Names:
  • MK-7339
  • LYNPARZA®

Biological: Bevacizumab
IV infusion
Other Name: AVASTIN®

Experimental: Pembrolizumab+Placebo for Olaparib
Participants receive carboplatin/paclitaxel via IV infusion for five 3-week cycles starting in Cycle 1 PLUS pembrolizumab 200 mg via IV infusion on Day 1 of each 3-week cycle for up to 35 cycles PLUS placebo for olaparib via oral tablet BID, starting with Cycle 7. Participants may also receive bevacizumab via IV infusion on Day 1 of each 3-week cycle.
Biological: Pembrolizumab
IV infusion
Other Names:
  • MK-3475
  • KEYTRUDA®

Drug: Carboplatin
IV infusion
Other Name: PARAPLATIN®

Drug: Paclitaxel
IV infusion
Other Name: TAXOL®

Drug: Placebo for olaparib
Oral tablet

Biological: Bevacizumab
IV infusion
Other Name: AVASTIN®

Active Comparator: Placebo for Pembrolizumab+Placebo for Olaparib
Participants receive carboplatin/paclitaxel via IV infusion for five 3-week cycles PLUS placebo for pembrolizumab (normal saline or dextrose) via IV infusion on Day 1 of each 3-week cycle for up to 35 cycles PLUS placebo for olaparib via oral tablet BID, starting with Cycle 7. Participants may also receive bevacizumab via IV infusion on Day 1 of each 3-week cycle.
Drug: Placebo for pembrolizumab
IV infusion
Other Name: normal saline or dextrose

Drug: Carboplatin
IV infusion
Other Name: PARAPLATIN®

Drug: Paclitaxel
IV infusion
Other Name: TAXOL®

Drug: Placebo for olaparib
Oral tablet

Biological: Bevacizumab
IV infusion
Other Name: AVASTIN®




Primary Outcome Measures :
  1. Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by the Investigator [ Time Frame: Up to approximately 6 years ]
    PFS is defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 based on Investigator assessment or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more lesions and the unequivocal progression of non-target lesions is also considered PD. The PFS per RECIST 1.1 as assessed by the Investigator will be presented.

  2. Overall Survival (OS) [ Time Frame: Up to approximately 6 years ]
    OS is defined as the time from the date of randomization to death due to any cause. The OS will be presented.


Secondary Outcome Measures :
  1. PFS Per RECIST 1.1 As Assessed by Blinded Independent Central Review [ Time Frame: Up to approximately 6 years ]
    PFS is defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on blinded independent central review assessment or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more lesions and the unequivocal progression of non-target lesions is also considered PD. The PFS per RECIST 1.1 as assessed by blinded independent central review will be presented.

  2. PFS After Next-line Treatment (PFS2) Following Discontinuation of Study Treatment As Assessed by the Investigator [ Time Frame: Up to approximately 78 months ]
    PFS2 is defined as the time from randomization until PD on next-line treatment or death due to any cause, whichever occurs first. The PFS2 per Investigator assessment will be presented.

  3. Number of Participants Who Experience an Adverse Event (AE) [ Time Frame: Up to approximately 73 months ]
    An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who experience an AE will be presented.

  4. Number of Participants Who Discontinue Study Treatment Due to an AE [ Time Frame: Up to approximately 6 years ]
    The number of participants who discontinue study treatment due to an AE will be presented.

  5. Change from Baseline in Global Health Status/Quality of Life (GHS/QoL) Score Using Questions from the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) [ Time Frame: Baseline and End of Study Participation (Up to approximately 6 years) ]
    Participants are asked to answer 2 questions from the EORTC QLQ-C30 about their GHS: "How would you rate your overall health during the past week?" and "How would you rate your overall quality of life during the past week?" Responses are based on a 7-point scale (1=Very poor; 7=Excellent), with a higher score indicating a better global health status. The change from baseline in GHS/QoL score of participants will be presented.

  6. Change from Baseline in Abdominal and Gastrointestinal (Abdominal/GI) Symptoms Score Using the EORTC Quality of Life Questionnaire-Ovarian Cancer (QLQ-OV28) Abdominal/GI Symptom Scale [ Time Frame: Baseline and End of Study Participation (Up to approximately 6 years) ]
    Participants are asked to answer 6 questions from the EORTC QoL Questionnaire-Ovarian Cancer (QLQ-OV28) abdominal/GI symptom scale about abdominal pain, bloated feeling in abdomen/stomach, changes in clothing fit, changes in bowel habit, flatulence and stomach fullness when eating. Responses are based on a 4-point scale (1=Not at all; 4=Very much), with a lower score indicating better abdominal/GI symptoms. The change from baseline in abdominal/GI symptom score of participants will be presented.

  7. Time to First Subsequent Anti-cancer Treatment (TFST) [ Time Frame: Up to approximately 6 years ]
    TFST is defined as the time from randomization to initiation of first subsequent anti-cancer treatment or death due to any cause, whichever occurs first. The TFST will be presented.

  8. Time to Second Subsequent Anti-cancer Treatment (TSST) [ Time Frame: Up to approximately 6 years ]
    TSST is defined as the time from randomization to initiation of second subsequent anti-cancer treatment or death due to any cause, whichever occurs first. The TSST will be presented.

  9. Time to Discontinuation of Study Treatment or Death (TDT) [ Time Frame: Up to approximately 6 years ]
    TDT is defined as the time from the date of randomization to discontinuation of study treatment or death due to any cause, whichever occurs first. The TDT will be presented.

  10. Pathological Complete Response (pCR) Rate [ Time Frame: Up to approximately 30 months ]
    pCR is defined as all surgical specimens collected during the interval debulking surgery are microscopically negative for malignancy. The pCR rate for all surgical specimens will be presented.

  11. Time Without Symptom of Disease Progression or Toxicity of Treatment (TWiST) [ Time Frame: Up to approximately 6 years ]
    TWiST is defined as the time from randomization to disease progression or treatment-related toxicity, whichever occurs first. The TWiST will be presented.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Has histologically confirmed International Federation of Gynecology and Obstetrics (FIGO) Stage III or Stage IV EOC (high-grade predominantly serous, endometrioid, 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 or 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 7 days prior to randomization
  • Is not pregnant, not breastfeeding, and 1 of the following conditions applies: a.) Not a woman of childbearing potential (WOCBP) OR b.) A WOCBP who agrees to follow contraceptive guidance during the treatment period and for at least 120 days following the last dose of pembrolizumab (or pembrolizumab placebo) and olaparib (or olaparib placebo) and at least 210 days following the last dose of chemotherapy or bevacizumab (if administered)
  • 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 (CNS) metastases and/or carcinomatous meningitis
  • 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 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 virus (HBV) or known active hepatitis C virus (HCV) infection
  • 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, defined as defined as systolic >140 mm Hg or diastolic >90 mm Hg documented by 2 blood pressure readings taken at least 1 hour apart. Note: This applies to participants who will receive bevacizumab. Use of antihypertensive medications to control blood pressure is allowed.
  • 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 randomization, 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 olaparib (or olaparib placebo) and at least 210 days following the last dose of chemotherapy or bevacizumab (if administered)
  • Has received prior treatment for advanced or metastatic 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
  • 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, enzalutamide, 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
  • Has received whole blood transfusions in the last 120 days prior to randomization
  • Is currently participating or has participated in a study of an investigational agent or has used an investigational device within 4 weeks of the first dose of study treatment
  • 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 2 weeks of randomization or has not recovered from any effects of any major surgery

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03740165


Contacts
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Contact: Toll Free Number 1-888-577-8839 Trialsites@merck.com

  Show 127 Study Locations
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
European Network for Gynaecological Oncological Trial Groups
Investigators
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Study Director: Medical Director Merck Sharp & Dohme Corp.

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Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT03740165     History of Changes
Other Study ID Numbers: 7339-001
2018-001973-25 ( EudraCT Number )
ENGOT-ov43 ( Other Identifier: European Network for Gynaecological Oncological Trial Groups )
MK-7339-001 ( Other Identifier: Merck )
KEYLYNK-001 ( Other Identifier: Merck )
194619 ( Registry Identifier: Japic-CTI )
First Posted: November 14, 2018    Key Record Dates
Last Update Posted: July 18, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Fallopian Tube Neoplasms
Peritoneal Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Fallopian Tube Diseases
Abdominal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Peritoneal Diseases
Paclitaxel
Albumin-Bound Paclitaxel
Bevacizumab
Carboplatin
Pembrolizumab
Olaparib
Antineoplastic Agents, Phytogenic
Antineoplastic Agents