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)
- Conditions
- Fallopian Tube CancerOvarian CancerPeritoneal Neoplasms
- Interventions
- Registration Number
- NCT03740165
- Lead Sponsor
- Merck Sharp & Dohme LLC
- 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) 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.
- 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
* 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.
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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- Female
- Target Recruitment
- 1367
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Pembrolizumab + Olaparib Docetaxel 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 who experience severe hypersensitivity reaction to paclitaxel or an AE requiring discontinuation of paclitaxel may receive docetaxel (75 mg/m\^2 Q3W) plus carboplatin AUC 5 Q3W after Sponsor consultation. Participants may also receive bevacizumab via IV infusion on Day 1 of each 3-week cycle at the Investigator's discretion. Pembrolizumab + Olaparib 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 who experience severe hypersensitivity reaction to paclitaxel or an AE requiring discontinuation of paclitaxel may receive docetaxel (75 mg/m\^2 Q3W) plus carboplatin AUC 5 Q3W after Sponsor consultation. Participants may also receive bevacizumab via IV infusion on Day 1 of each 3-week cycle at the Investigator's discretion. Pembrolizumab + Placebo for Olaparib Carboplatin 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 who experience severe hypersensitivity reaction to paclitaxel or an AE requiring discontinuation of paclitaxel may receive docetaxel (75 mg/m\^2 Q3W) plus carboplatin AUC 5 Q3W after Sponsor consultation. Participants may also receive bevacizumab via IV infusion on Day 1 of each 3-week cycle at the Investigator's discretion. Placebo for Pembrolizumab + Placebo for Olaparib 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 who experience severe hypersensitivity reaction to paclitaxel or an AE requiring discontinuation of paclitaxel may receive docetaxel (75 mg/m\^2 Q3W) plus carboplatin AUC 5 Q3W after Sponsor consultation. Participants may also receive bevacizumab via IV infusion on Day 1 of each 3-week cycle at the Investigator's discretion. Pembrolizumab + Placebo for Olaparib 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 who experience severe hypersensitivity reaction to paclitaxel or an AE requiring discontinuation of paclitaxel may receive docetaxel (75 mg/m\^2 Q3W) plus carboplatin AUC 5 Q3W after Sponsor consultation. Participants may also receive bevacizumab via IV infusion on Day 1 of each 3-week cycle at the Investigator's discretion. Placebo for Pembrolizumab + Placebo for Olaparib Placebo for pembrolizumab 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 who experience severe hypersensitivity reaction to paclitaxel or an AE requiring discontinuation of paclitaxel may receive docetaxel (75 mg/m\^2 Q3W) plus carboplatin AUC 5 Q3W after Sponsor consultation. Participants may also receive bevacizumab via IV infusion on Day 1 of each 3-week cycle at the Investigator's discretion. Pembrolizumab + Olaparib Pembrolizumab 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 who experience severe hypersensitivity reaction to paclitaxel or an AE requiring discontinuation of paclitaxel may receive docetaxel (75 mg/m\^2 Q3W) plus carboplatin AUC 5 Q3W after Sponsor consultation. Participants may also receive bevacizumab via IV infusion on Day 1 of each 3-week cycle at the Investigator's discretion. Pembrolizumab + Olaparib Carboplatin 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 who experience severe hypersensitivity reaction to paclitaxel or an AE requiring discontinuation of paclitaxel may receive docetaxel (75 mg/m\^2 Q3W) plus carboplatin AUC 5 Q3W after Sponsor consultation. Participants may also receive bevacizumab via IV infusion on Day 1 of each 3-week cycle at the Investigator's discretion. Pembrolizumab + Olaparib Paclitaxel 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 who experience severe hypersensitivity reaction to paclitaxel or an AE requiring discontinuation of paclitaxel may receive docetaxel (75 mg/m\^2 Q3W) plus carboplatin AUC 5 Q3W after Sponsor consultation. Participants may also receive bevacizumab via IV infusion on Day 1 of each 3-week cycle at the Investigator's discretion. Pembrolizumab + Olaparib Bevacizumab 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 who experience severe hypersensitivity reaction to paclitaxel or an AE requiring discontinuation of paclitaxel may receive docetaxel (75 mg/m\^2 Q3W) plus carboplatin AUC 5 Q3W after Sponsor consultation. Participants may also receive bevacizumab via IV infusion on Day 1 of each 3-week cycle at the Investigator's discretion. Pembrolizumab + Placebo for Olaparib Pembrolizumab 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 who experience severe hypersensitivity reaction to paclitaxel or an AE requiring discontinuation of paclitaxel may receive docetaxel (75 mg/m\^2 Q3W) plus carboplatin AUC 5 Q3W after Sponsor consultation. Participants may also receive bevacizumab via IV infusion on Day 1 of each 3-week cycle at the Investigator's discretion. Pembrolizumab + Placebo for Olaparib Paclitaxel 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 who experience severe hypersensitivity reaction to paclitaxel or an AE requiring discontinuation of paclitaxel may receive docetaxel (75 mg/m\^2 Q3W) plus carboplatin AUC 5 Q3W after Sponsor consultation. Participants may also receive bevacizumab via IV infusion on Day 1 of each 3-week cycle at the Investigator's discretion. Pembrolizumab + Placebo for Olaparib Bevacizumab 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 who experience severe hypersensitivity reaction to paclitaxel or an AE requiring discontinuation of paclitaxel may receive docetaxel (75 mg/m\^2 Q3W) plus carboplatin AUC 5 Q3W after Sponsor consultation. Participants may also receive bevacizumab via IV infusion on Day 1 of each 3-week cycle at the Investigator's discretion. Pembrolizumab + Placebo for Olaparib Docetaxel 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 who experience severe hypersensitivity reaction to paclitaxel or an AE requiring discontinuation of paclitaxel may receive docetaxel (75 mg/m\^2 Q3W) plus carboplatin AUC 5 Q3W after Sponsor consultation. Participants may also receive bevacizumab via IV infusion on Day 1 of each 3-week cycle at the Investigator's discretion. Placebo for Pembrolizumab + Placebo for Olaparib Carboplatin 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 who experience severe hypersensitivity reaction to paclitaxel or an AE requiring discontinuation of paclitaxel may receive docetaxel (75 mg/m\^2 Q3W) plus carboplatin AUC 5 Q3W after Sponsor consultation. Participants may also receive bevacizumab via IV infusion on Day 1 of each 3-week cycle at the Investigator's discretion. Placebo for Pembrolizumab + Placebo for Olaparib Docetaxel 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 who experience severe hypersensitivity reaction to paclitaxel or an AE requiring discontinuation of paclitaxel may receive docetaxel (75 mg/m\^2 Q3W) plus carboplatin AUC 5 Q3W after Sponsor consultation. Participants may also receive bevacizumab via IV infusion on Day 1 of each 3-week cycle at the Investigator's discretion. Placebo for Pembrolizumab + Placebo for Olaparib Paclitaxel 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 who experience severe hypersensitivity reaction to paclitaxel or an AE requiring discontinuation of paclitaxel may receive docetaxel (75 mg/m\^2 Q3W) plus carboplatin AUC 5 Q3W after Sponsor consultation. Participants may also receive bevacizumab via IV infusion on Day 1 of each 3-week cycle at the Investigator's discretion. Placebo for Pembrolizumab + Placebo for Olaparib Bevacizumab 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 who experience severe hypersensitivity reaction to paclitaxel or an AE requiring discontinuation of paclitaxel may receive docetaxel (75 mg/m\^2 Q3W) plus carboplatin AUC 5 Q3W after Sponsor consultation. Participants may also receive bevacizumab via IV infusion on Day 1 of each 3-week cycle at the Investigator's discretion.
- Primary Outcome Measures
Name Time Method Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by the Investigator in Participants with Programmed Death-Ligand 1 (PD-L1)-Positive Tumors (Combined Positive Score [CPS]≥10) Up to approximately 57 months 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 reported for participants with PD-L1-positive (CPS≥10) tumors.
PFS Per RECIST 1.1 as Assessed by the Investigator in All Participants Up to approximately 57 months 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 reported for all participants.
- Secondary Outcome Measures
Name Time Method Overall Survival (OS) in All Participants 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 reported for all participants.
OS in Participants with PDL-1 Positive Tumors (CPS ≥ 10) 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 reported for all participants with PD-L1 positive tumors (CPS≥10).
PFS Per RECIST 1.1 as Assessed by Blinded Independent Central Review (BICR) in Participants with PD-L1-Positive Tumors (CPS≥10) Up to approximately 57 months 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 reported for participants with PD-L1-positive (CPS≥10) tumors.
Number of Participants Who Discontinue Study Treatment Due to an AE Up to approximately 6 years 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 discontinue study treatment due to an AE will be reported.
Mean 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) 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 mean change from baseline in GHS/QoL score of participants will be reported.
Time to First Subsequent Anti-cancer Treatment (TFST) 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 reported.
PFS Per RECIST 1.1 as Assessed by BICR in All Participants Up to approximately 57 months 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 reported for all participants.
PFS After Second-line Treatment (PFS2) Following Discontinuation of Study Treatment as Assessed by the Investigator in Participants with PD-L1-Positive Tumors (CPS≥10) Up to approximately 78 months PFS2 is defined as the time from randomization until PD (clinical or radiological) after second-line treatment or death due to any cause, whichever occurs first. The PFS2 per Investigator assessment will be reported for participants with PD-L1-positive (CPS≥10) tumors.
PFS2 Following Discontinuation of Study Treatment as Assessed by the Investigator in All Participants Up to approximately 78 months PFS2 is defined as the time from randomization until PD (clinical or radiological) after second-line treatment or death due to any cause, whichever occurs first. The PFS2 per Investigator assessment will be reported for all participants.
Number of Participants Who Experience an Adverse Event (AE) 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 reported.
Mean 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 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 mean change from baseline in abdominal/GI symptom score of participants will be reported.
Time to deterioration (TTD) of GHS/QoL score using EORTC QLQ-C30 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. TTD is defined as the time from the first GHS/QoL assessment to deterioration (defined as ≥10-point decrease in GHS/QoL score from baseline) or death, whichever occurs first. The TTD in GHS/QoL score of participants will be reported.
Time to deterioration (TTD) of abdominal/GI symptoms using EORTC QLQ-OV28 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. TTD is defined as the time from the first EORTC QLQ-OV28 assessment to deterioration (defined as ≥10-point decrease in EORTC QLQ-OV28 score from baseline) or death, whichever occurs first. The TTD in abdominal/GI symptom score of participants will be reported.
Time to Second Subsequent Anti-cancer Treatment (TSST) 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 reported.
Time to Discontinuation of Study Treatment or Death (TDT) 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 reported.
Pathological Complete Response (pCR) Rate 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 reported.
Trial Locations
- Locations (227)
The Bing Cancer Center ( Site 0044)
🇺🇸Columbus, Ohio, United States
Parkland Hospital ( Site 0081)
🇺🇸Dallas, Texas, United States
UT Southwestern Medical Center ( Site 0046)
🇺🇸Dallas, Texas, United States
Wits Clinical Research ( Site 1702)
🇿🇦Johannesburg, Gauteng, South Africa
Cancercare ( Site 1706)
🇿🇦Cape Town, Western Cape, South Africa
Oncomedica S.A. ( Site 2911)
🇨🇴Monteria, Cordoba, Colombia
UZ Gent ( Site 0307)
🇧🇪Gent, Oost-Vlaanderen, Belgium
The Oncology Centre ( Site 1709)
🇿🇦Durban, Kwazulu-Natal, South Africa
Hospital de Caridade de Ijui ( Site 2712)
🇧🇷Ijui, Rio Grande Do Sul, Brazil
Centre D Oncologie de Gentilly ( Site 0609)
🇫🇷Nancy, Meurthe-et-Moselle, France
Staedtisches Krankenhaus Kiel GmbH ( Site 0709)
🇩🇪Kiel, Schleswig-Holstein, Germany
Kaiser Permanente Oncology Clinical Trial - San Francisco ( Site 0078)
🇺🇸San Francisco, California, United States
Tom Baker Cancer Centre ( Site 0200)
🇨🇦Calgary, Alberta, Canada
Kingston Health Sciences Centre ( Site 0207)
🇨🇦Kingston, Ontario, Canada
CIUSSS de l Est de L Ile de Montreal - Hopital Maisonneuve-Rosemont ( Site 0219)
🇨🇦Montreal, Quebec, Canada
Northeast Georgia Medical Center ( Site 0029)
🇺🇸Gainesville, Georgia, United States
University of Alabama at Birmingham (UAB) ( Site 0036)
🇺🇸Birmingham, Alabama, United States
Saint Vincent Hospital and Health Center ( Site 0012)
🇺🇸Indianapolis, Indiana, United States
Kaiser Permanente Oncology Clinical Trial - Walnut Creek ( Site 0080)
🇺🇸Walnut Creek, California, United States
Kaiser Permanente Oncology Clinical Trial - Santa Clara ( Site 0079)
🇺🇸Santa Clara, California, United States
Saint Dominic - Jackson Memorial Hospital ( Site 0072)
🇺🇸Jackson, Mississippi, United States
Kaiser Permanente Oncology Clinical Trials-Roseville ( Site 0084)
🇺🇸Roseville, California, United States
Kaiser Permanente Oncology Clinical Trials-Sacramento ( Site 0083)
🇺🇸Sacramento, California, United States
Smilow Cancer Center at Yale-New Haven ( Site 0057)
🇺🇸New Haven, Connecticut, United States
University of Chicago ( Site 0049)
🇺🇸Chicago, Illinois, United States
Weinberg Cancer Institute at Franklin Square ( Site 0035)
🇺🇸Baltimore, Maryland, United States
University of Iowa Hospital and Clinics ( Site 0005)
🇺🇸Iowa City, Iowa, United States
Cliniques Universitaires Saint-Luc ( Site 0312)
🇧🇪Brussels, Bruxelles-Capitale, Region De, Belgium
AZ Maria Middelares Gent ( Site 0300)
🇧🇪Gent, Oost-Vlaanderen, Belgium
Oncology/Hematology Care Clinical Trials, LLC ( Site 8001)
🇺🇸Cincinnati, Ohio, United States
Centre Hospitalier de l'Ardenne ( Site 0303)
🇧🇪Libramont, Luxembourg, Belgium
MEDICAL COLLEGE OF WISCONSIN ( Site 0064)
🇺🇸Milwaukee, Wisconsin, United States
Cairns and Hinterland Hospital and Health Service ( Site 2201)
🇦🇺Cairns, Queensland, Australia
Jessa Ziekenhuis ( Site 0309)
🇧🇪Hasselt, Limburg, Belgium
Centro Investigación del Cáncer James Lind ( Site 2810)
🇨🇱Temuco, Araucania, Chile
Fundacion Arturo Lopez Perez FALP ( Site 2800)
🇨🇱Santiago, Region M. De Santiago, Chile
UZ Leuven Campus Gasthuisberg ( Site 0306)
🇧🇪Leuven, Antwerpen, Belgium
Hospital Bruno Born ( Site 2704)
🇧🇷Lajeado, Rio Grande Do Sul, Brazil
Real e Benemerita Associacao Portuguesa de Beneficencia ( Site 2710)
🇧🇷Sao Paulo, Brazil
Virginia Cancer Specialists, PC ( Site 8003)
🇺🇸Gainesville, Virginia, United States
St George Hospital ( Site 2207)
🇦🇺Kogarah, New South Wales, Australia
Hospital Araujo Jorge Associacao de Combate ao Cancer de Goias ( Site 2708)
🇧🇷Goiania, Goias, Brazil
Instituto do Cancer do Estado de Sao Paulo - ICESP ( Site 2714)
🇧🇷Sao Paulo, Brazil
Hospital Nossa Senhora Da Conceicao ( Site 2703)
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Instituto Nacional de Cancer Hospital do Cancer II ( Site 2700)
🇧🇷Rio de Janeiro, Brazil
Iram Cancer Research ( Site 2809)
🇨🇱Santiago, Region M. De Santiago, Chile
Pontificia Universidad Catolica de Chile ( Site 2805)
🇨🇱Santiago, Region M. De Santiago, Chile
Hemato Oncologos S.A. ( Site 2906)
🇨🇴Cali, Valle Del Cauca, Colombia
Biomelab S A S ( Site 2900)
🇨🇴Barranquilla, Atlantico, Colombia
Clinica Colsanitas S.A. Sede Clinica Universitaria Colombia ( Site 2912)
🇨🇴Bogota, Distrito Capital De Bogota, Colombia
Sociedad de Oncología Y Hematología del Cesar S.A.S. ( Site 2913)
🇨🇴Valledupar, Cesar, Colombia
Oncocentro ( Site 2801)
🇨🇱Vina del Mar, Valparaiso, Chile
Hopital Prive Jean Mermoz ( Site 0607)
🇫🇷Lyon, Auvergne, France
Istituto Europeo di Oncologia ( Site 1100)
🇮🇹Milano, Lombardia, Italy
CHU de Brest -Site Hopital Morvan ( Site 0616)
🇫🇷Brest, Bretagne, France
Caritas Klinikum Saarbruecken St. Theresia ( Site 0702)
🇩🇪Saarbruecken, Saarland, Germany
Centre Paul Strauss ( Site 0615)
🇫🇷Strasbourg, Bas-Rhin, France
Marienhospital Stuttgart Vincenz von Paul Kliniken gGmbH ( Site 0707)
🇩🇪Stuttgart, Baden-Wurttemberg, Germany
Institut de Cancerologie du Gard - CHU Caremeau ( Site 0610)
🇫🇷Nimes, Gard, France
HELIOS Klinikum Krefeld ( Site 0715)
🇩🇪Krefeld, Nordrhein-Westfalen, Germany
Orszagos Onkologiai Intezet ( Site 0800)
🇭🇺Budapest, Hungary
Ospedale Cannizzaro ( Site 1110)
🇮🇹Catania, Italy
Uniklinik RWTH Aachen ( Site 0718)
🇩🇪Aachen, Nordrhein-Westfalen, Germany
Soroka Medical Center ( Site 1006)
🇮🇱Beer-Sheva, Israel
Debreceni Egyetem Klinikai Kozpont ( Site 0801)
🇭🇺Debrecen, Hungary
Uzsoki Utcai Korhaz ( Site 0803)
🇭🇺Budapest, Hungary
Istituto Oncologico Veneto IRCCS ( Site 1113)
🇮🇹Padova, Veneto, Italy
ASST Lecco. Ospedale A. Manzoni ( Site 1101)
🇮🇹Lecco, Italy
Azienda Ospedaliera Policlinico Umberto I ( Site 1111)
🇮🇹Roma, Italy
A.O. Univ. S. M. della Misericordia ( Site 1114)
🇮🇹Udine, Italy
Policlinico Universitario Gemelli ( Site 1105)
🇮🇹Roma, Italy
Swietokrzyskie Centrum Onkologii SPZOZ ( Site 1410)
🇵🇱Kielce, Swietokrzyskie, Poland
Istanbul Universitesi Istanbul Tip Fakultesi ( Site 1900)
🇹🇷Istanbul, Turkey
Bakirkoy Sadi Konuk Egitim ve Arastirma Hastanesi ( Site 1907)
🇹🇷Istanbul, Turkey
Outeniqua Cancercare Oncology Unit ( Site 1708)
🇿🇦George, Western Cape, South Africa
Instituto Valenciano de Oncologia ( Site 1601)
🇪🇸Valencia, Valenciana, Comunitat, Spain
Grigoriev Institute for medical Radiology NAMS of Ukraine ( Site 2180)
🇺🇦Kharkiv, Kharkivska Oblast, Ukraine
Uludag Universitesi Tip Fakultesi ( Site 1904)
🇹🇷Bursa, Turkey
Sakarya Universitesi Tip Fakultesi Hastanesi ( Site 1906)
🇹🇷Sakarya, Turkey
RMI - Sumy Regional Clinical Oncology Dispensary ( Site 2191)
🇺🇦Sumy, Sumska Oblast, Ukraine
Hospital de Terrassa ( Site 1606)
🇪🇸Terrassa, Barcelona, Spain
MI Precarpathian Clinical Oncology Center ( Site 2181)
🇺🇦Ivano-Frankivsk, Ivano-Frankivska Oblast, Ukraine
Medipol Universite Hastanesi ( Site 1909)
🇹🇷Istanbul, Turkey
MI Odessa Regional Oncological Centre ( Site 2121)
🇺🇦Odesa, Odeska Oblast, Ukraine
National Defense Medical College Hospital ( Site 2608)
🇯🇵Tokorozawa, Saitama, Japan
Sandton Oncology Medical Group PTY LTD ( Site 1712)
🇿🇦Sandton, Gauteng, South Africa
Washington University - School of Medicine ( Site 0062)
🇺🇸Saint Louis, Missouri, United States
Clinica Universitaria de Navarra ( Site 1600)
🇪🇸Madrid, Spain
Complejo Hospitalario Universitario A Coruna. CHUAC ( Site 1608)
🇪🇸A Coruna, La Coruna, Spain
Klinikum Chemnitz gGmbH ( Site 0711)
🇩🇪Chemnitz, Sachsen, Germany
Universitaetsklinikum Duesseldorf ( Site 0704)
🇩🇪Duesseldorf, Nordrhein-Westfalen, Germany
Rabin Medical Center ( Site 1004)
🇮🇱Petah Tikva, Israel
Fakultni nemocnice Ostrava ( Site 0403)
🇨🇿Ostrava-Poruba, Moravskoslezsky Kraj, Czechia
Fakultni nemocnice Brno ( Site 0404)
🇨🇿Brno, Brno-mesto, Czechia
Fakultni nemocnice Olomouc ( Site 0402)
🇨🇿Olomouc, Czechia
Hopital Tenon ( Site 0612)
🇫🇷Paris, France
Nemocnice Na Bulovce ( Site 0401)
🇨🇿Praha, Praha, Hlavni Mesto, Czechia
Charite Campus Virchow-Klinikum - CVK ( Site 0700)
🇩🇪Berlin, Germany
Cancer Care Langenhoven Drive Oncology Centre ( Site 1701)
🇿🇦Port Elizabeth, Eastern Cape, South Africa
The Credit Valley Hospital ( Site 0206)
🇨🇦Mississauga, Ontario, Canada
Sarasota Memorial Hospital ( Site 0023)
🇺🇸Sarasota, Florida, United States
Memorial Health University Medical Center ( Site 0011)
🇺🇸Savannah, Georgia, United States
OSU Wexner Medical Center ( Site 0076)
🇺🇸Hilliard, Ohio, United States
Ballarat Health Services ( Site 2202)
🇦🇺Ballarat, Victoria, Australia
Instituto do Cancer do Ceara ( Site 2707)
🇧🇷Fortaleza, Ceara, Brazil
Hillel Yaffe Medical Center ( Site 1011)
🇮🇱Hadera, Israel
University of Arizona Cancer Center ( Site 0074)
🇺🇸Tucson, Arizona, United States
Disney Family Cancer Center ( Site 0042)
🇺🇸Burbank, California, United States
Kaiser Permanente Oncology Clinical Trial -Oakland ( Site 0077)
🇺🇸Oakland, California, United States
Kaiser Permanente N. CA Regional Oncology Clinical Trials ( Site 0008)
🇺🇸Vallejo, California, United States
Emory School of Medicine ( Site 0053)
🇺🇸Atlanta, Georgia, United States
Rush University Medical Center ( Site 0019)
🇺🇸Chicago, Illinois, United States
Dr. Sudarshan K. Sharma, LTD ( Site 0061)
🇺🇸Hinsdale, Illinois, United States
Northwell Health- Monter Cancer Center ( Site 0075)
🇺🇸Lake Success, New York, United States
MD Anderson Cancer Center at Cooper ( Site 0067)
🇺🇸Camden, New Jersey, United States
Dartmouth Hitchcock Medical Center ( Site 0024)
🇺🇸Lebanon, New Hampshire, United States
Nebraska Methodist Hospital ( Site 0063)
🇺🇸Omaha, Nebraska, United States
Holy Name Medical Center ( Site 0037)
🇺🇸Teaneck, New Jersey, United States
Miami Valley Hospital [Dayton, OH] ( Site 0073)
🇺🇸Centerville, Ohio, United States
Texas Oncology, P.A. - Bedford ( Site 8005)
🇺🇸Bedford, Texas, United States
Texas Oncology-Dallas Presbyterian Hospital ( Site 8004)
🇺🇸Dallas, Texas, United States
Women and Infants Hospital [Providence, RI] ( Site 0039)
🇺🇸Providence, Rhode Island, United States
Texas Oncology, P.A. Texas Oncology-Tyler ( Site 8006)
🇺🇸Tyler, Texas, United States
Monash Health ( Site 2204)
🇦🇺Clayton, Victoria, Australia
Sunshine Hospital. ( Site 2205)
🇦🇺St Albans, Victoria, Australia
Grand Hopital de Charleroi ( Site 0302)
🇧🇪Charleroi, Hainaut, Belgium
Hospital Erasto Gaertner ( Site 2716)
🇧🇷Curitiba, Parana, Brazil
Taichung Veterans General Hospital ( Site 2510)
🇨🇳Taichung, Taiwan
Clinica de Pesquisas e Ctro de Estudos Onc. Ginecol. e Mamaria Ltda ( Site 2706)
🇧🇷Sao Paulo, Brazil
Princess Margaret Hospital.. ( Site 0202)
🇨🇦Toronto, Ontario, Canada
CIUSSS du Saguenay-Lac-St-Jean ( Site 0218)
🇨🇦Chicoutimi, Quebec, Canada
Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0208)
🇨🇦Montreal, Quebec, Canada
Royal Victoria Hospital McGill University Health Centre ( Site 0211)
🇨🇦Montreal, Quebec, Canada
Instituto Nacional de Cancerologia E.S.E ( Site 2910)
🇨🇴Bogota, Distrito Capital De Bogota, Colombia
Vseobecna fakultni nemocnice v Praze ( Site 0400)
🇨🇿Praha, Praha, Hlavni Mesto, Czechia
Hopital de la Timone ( Site 0617)
🇫🇷Marseille, Bouches-du-Rhone, France
Institut de Cancerologie Lucien Neuwirth ( Site 0613)
🇫🇷Saint-Priest-en-Jarez, Loire, France
Gynaekologisches Zentrum ( Site 0712)
🇩🇪Bonn, Nordrhein-Westfalen, Germany
Klinikum Rechts der Isar. Technischen Universitaet Muenchen ( Site 0710)
🇩🇪Muenchen, Bayern, Germany
Universitaetsklinikum Muenster ( Site 0720)
🇩🇪Muenster, Nordrhein-Westfalen, Germany
Klinikum Dortmund gGmbH ( Site 0717)
🇩🇪Dortmund, Nordrhein-Westfalen, Germany
Pecsi Tudomanyegyetem Klinikai Kozpont ( Site 0805)
🇭🇺Pecs, Baranya, Hungary
Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi Oktato Korhaz ( Site 0802)
🇭🇺Miskolc, Borsod-Abauj-Zemplen, Hungary
Shaare Zedek Medical Center ( Site 1005)
🇮🇱Jerusalem, Israel
Carmel Medical Center ( Site 1007)
🇮🇱Haifa, Israel
Rambam Medical Center ( Site 1002)
🇮🇱Haifa, Israel
Edith Wolfson Medical Center ( Site 1003)
🇮🇱Holon, Israel
Chaim Sheba Medical Center ( Site 1000)
🇮🇱Ramat Gan, Israel
Sourasky Medical Center ( Site 1001)
🇮🇱Tel Aviv, Israel
IRCCS Giovanni Paolo II. Ospedale Oncologico ( Site 1108)
🇮🇹Bari, Abruzzo, Italy
Sacro Cuore di Gesu Fatebenefratelli ( Site 1112)
🇮🇹Benevento, Italy
A.O.U. Citta della Salute e della Scienza di Torino ( Site 1104)
🇮🇹Torino, Piemonte, Italy
Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 1115)
🇮🇹Milano, Italy
A.O.U. Federico II di Napoli ( Site 1107)
🇮🇹Napoli, Italy
National Hospital Organization Shikoku Cancer Center ( Site 2601)
🇯🇵Matsuyama, Ehime, Japan
Gunma Prefectural Cancer Center ( Site 2609)
🇯🇵Ota, Gunma, Japan
Presidio Ospedaliero Santa Chiara ( Site 1109)
🇮🇹Trento, Italy
National Cancer Center Hospital East ( Site 2602)
🇯🇵Kashiwa, Chiba, Japan
Saitama Cancer Center ( Site 2614)
🇯🇵Kitaadachi-gun, Saitama, Japan
St. Marianna University School of Medicine Hospital ( Site 2613)
🇯🇵Kawasaki, Kanagawa, Japan
Ehime University Hospital ( Site 2600)
🇯🇵Toon, Ehime, Japan
Iwate Medical University Hospital ( Site 2606)
🇯🇵Shiwa-gun, Iwate, Japan
University of the Ryukyus Hospital ( Site 2616)
🇯🇵Nakagami-gun, Okinawa, Japan
Hokkaido University Hospital ( Site 2607)
🇯🇵Sapporo, Hokkaido, Japan
Niigata Cancer Center Hospital ( Site 2618)
🇯🇵Niigata, Japan
Kyorin University Hospital ( Site 2610)
🇯🇵Mitaka, Tokyo, Japan
Saitama Medical University International Medical Center ( Site 2604)
🇯🇵Hidaka, Saitama, Japan
Osaka International Cancer Institute ( Site 2617)
🇯🇵Osaka, Japan
Kagoshima City Hospital ( Site 2612)
🇯🇵Kagoshima, Japan
National Cancer Center Hospital ( Site 2605)
🇯🇵Tokyo, Japan
Asan Medical Center ( Site 2402)
🇰🇷Seoul, Korea, Republic of
Seoul National University Bundang Hospital ( Site 2404)
🇰🇷Seongnam-si, Kyonggi-do, Korea, Republic of
Seoul National University Hospital ( Site 2403)
🇰🇷Seoul, Korea, Republic of
Severance Hospital Yonsei University Health System ( Site 2400)
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center ( Site 2401)
🇰🇷Seoul, Korea, Republic of
Szpitale Pomorskie Sp. z o.o. ( Site 1407)
🇵🇱Gdynia, Pomorskie, Poland
Bialostockie Centrum Onkologii ( Site 1412)
🇵🇱Bialystok, Podlaskie, Poland
Szpital Kliniczny im. Przemienienia Panskiego Uniwersytetu Medycznego im. K. Marcinkowskiego w Pozna
🇵🇱Poznan, Wielkopolskie, Poland
Narodowy Instytut Onkologii - Oddzial w Gliwicach ( Site 1406)
🇵🇱Gliwice, Slaskie, Poland
Republican Clinical Oncology Dispensary of Republic of Bashkortostan ( Site 1507)
🇷🇺Ufa, Baskortostan, Respublika, Russian Federation
Arkhangelsk Clinical Oncological Dispensary ( Site 1508)
🇷🇺Arkhangelsk, Arkhangel Skaya Oblast, Russian Federation
A. Tsyb Medical Radiological Research Center ( Site 1513)
🇷🇺Obninsk, Kaluzskaja Oblast, Russian Federation
City Clinical Oncology Center ( Site 1505)
🇷🇺Saint Petersburg, Sankt-Peterburg, Russian Federation
FSBI National Medical Oncology Research Center n.a. N.N. Blokhina ( Site 1500)
🇷🇺Moscow, Moskva, Russian Federation
Medical Rehabilitation Center ( Site 1502)
🇷🇺Moscow, Moskva, Russian Federation
National Medical Research Center of Oncology N.A. N.N. Petrov ( Site 1504)
🇷🇺Saint-Petersburg, Sankt-Peterburg, Russian Federation
FSCC of Special Types of Med. Care and Technologies ( Site 1503)
🇷🇺Moscow, Moskva, Russian Federation
Groote Schuur Hospital ( Site 1704)
🇿🇦Cape Town, Gauteng, South Africa
Republican Clinical Oncology Dispensary of Tatarstan MoH ( Site 1509)
🇷🇺Kazan, Tatarstan, Respublika, Russian Federation
Wilgers Oncology Centre ( Site 1705)
🇿🇦Pretoria, Gauteng, South Africa
Curo Oncology ( Site 1710)
🇿🇦Pretoria, Gauteng, South Africa
Little Company of Mary Hospital ( Site 1700)
🇿🇦Pretoria, Gauteng, South Africa
Department of Medical Oncology ( Site 1703)
🇿🇦Pretoria, Gauteng, South Africa
Instituto Catalan de Oncologia ICO - Hospital Duran i Reynals ( Site 1603)
🇪🇸Hospitalet de Llobregat, Barcelona, Spain
Hospital General Universitario de Valencia ( Site 1610)
🇪🇸Valencia, Valenciana, Comunitat, Spain
Hospital Universitario Lucus Augusti ( Site 1609)
🇪🇸Lugo, Spain
Hospital Provincial San Pedro de Alcantara ( Site 1607)
🇪🇸Caceres, Spain
Hospital Universitario de Donostia ( Site 1602)
🇪🇸Donostia, Gipuzkoa, Spain
Xarxa Assistencial Universitaria Manresa ( Site 1605)
🇪🇸Manresa, Barcelona, Spain
Hospital Universitario Virgen del Rocio ( Site 1604)
🇪🇸Sevilla, Spain
Changhua Christian Hospital ( Site 2507)
🇨🇳Changhua, Taiwan
China Medical University Hospital ( Site 2506)
🇨🇳Taichung, Taiwan
MacKay Memorial Hospital ( Site 2500)
🇨🇳Taipei, Taiwan
Istanbul Acibadem University Atakent Hospital ( Site 1902)
🇹🇷Kucukcekmece, Istanbul, Turkey
Taipei Veterans General Hospital ( Site 2503)
🇨🇳Taipei, Taiwan
National Cheng Kung University Hospital ( Site 2508)
🇨🇳Tainan, Taiwan
Linkou Chang Gung Memorial Hospital ( Site 2501)
🇨🇳Taoyuan, Taiwan
Akdeniz Universitesi Tıp Fakultesi ( Site 1901)
🇹🇷Antalya, Turkey
Etlik Zubeyde Hanim Kadin Hastaliklari Egitim ve Arastirma Hastanesi ( Site 1903)
🇹🇷Ankara, Turkey
Ankara UTF Cebeci Arastırma ve Uygulama Hastanesi ( Site 1905)
🇹🇷Ankara, Turkey
Centro Oncologico Antofagasta ( Site 2804)
🇨🇱Antofagasta, Chile
Municipal non-profit Enterprise Khmelnytskyi Regional Antitu-Gynecological Oncology department, Poli
🇺🇦Khmelnytskyi, Khmelnytska Oblast, Ukraine
Sociedad Oncovida S.A. ( Site 2807)
🇨🇱Santiago, Region M. De Santiago, Chile
Centro de Investigacion y desarrollo Oncologico SpA - CIDO SpA ( Site 2808)
🇨🇱Temuco, Araucania, Chile
Institut Gustave Roussy ( Site 0600)
🇫🇷Villejuif, Val-de-Marne, France
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie (
🇵🇱Warszawa, Mazowieckie, Poland
Lviv State Oncology Regional Treatment and Diagnostic Center ( Site 2170)
🇺🇦Lviv, Lvivska Oblast, Ukraine
Kyiv City Clinical Oncological Center ( Site 2140)
🇺🇦Kyiv, Ukraine
CHU de Liege ( Site 0310)
🇧🇪Liège, Liege, Belgium
Imelda Ziekenhuis Bonheiden ( Site 0301)
🇧🇪Bonheiden, Antwerpen, Belgium
National Taiwan University Hospital ( Site 2502)
🇨🇳Taipei, Taiwan
Central City Clinical Hospital ( Site 2150)
🇺🇦Uzhgorod, Zakarpatska Oblast, Ukraine
University of Kentucky ( Site 0045)
🇺🇸Lexington, Kentucky, United States
Sanford Gynecology Oncology ( Site 0004)
🇺🇸Sioux Falls, South Dakota, United States
Sanford Roger Maris Cancer Center ( Site 0082)
🇺🇸Fargo, North Dakota, United States
Centro Medico Imbanaco de Cali S.A ( Site 2909)
🇨🇴Cali, Valle Del Cauca, Colombia
Cape Town Oncology Trials Pty Ltd ( Site 1707)
🇿🇦Kraaifontein, Western Cape, South Africa