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 / GOG-3036)
| Registry | NCT03740165 |
|---|---|
| Status | Completed |
| Phase | Phase 3 |
| Study type | Interventional; randomized, parallel, masking: quadruple, treatment |
| Enrollment | 1367 (Actual) |
| Sponsor | Merck Sharp & Dohme LLC (Industry); collaborators: European Network of Gynaecological Oncological Trial Groups (ENGOT), Gynecologic Oncology Group |
| Conditions | Ovarian Cancer, Fallopian Tube Cancer, Peritoneal Neoplasms |
| Interventions | Pembrolizumab, Placebo for pembrolizumab, Carboplatin, Paclitaxel, Olaparib, Placebo for olaparib, Bevacizumab, Docetaxel (Biological, drug) |
| Dates | start 2018-12-18, primary completion 2024-08-26, completion 2026-04-14, first posted 2018-11-14, last updated 2026-08-19 |
| Locations | 227 sites in United States, Australia, Belgium, Brazil, Canada, Chile, Colombia, Czechia and 14 more countries |
Related Papers Related Patents Related Grants Related Experts
All trials for Ovarian Cancer All trials for Fallopian Tube Cancer All trials of Pembrolizumab All trials of Placebo for pembrolizumab
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.
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, and will receive carboplatin/paclitaxel* for 5 cycles plus:
* 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.
| Arm | Type | Interventions | Description |
|---|---|---|---|
| Carboplatin + Paclitaxel + Pembrolizumab + Olaparib | Experimental | Biological: Pembrolizumab; Drug: Carboplatin; Drug: Paclitaxel; Drug: Olaparib; Biological: Bevacizumab; Drug: 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. |
| Carboplatin + Paclitaxel + Pembrolizumab | Experimental | Biological: Pembrolizumab; Drug: Carboplatin; Drug: Paclitaxel; Drug: Placebo for olaparib; Biological: Bevacizumab; Drug: 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. |
| Carboplatin + Paclitaxel | Active comparator | Drug: Placebo for pembrolizumab; Drug: Carboplatin; Drug: Paclitaxel; Drug: Placebo for olaparib; Biological: Bevacizumab; Drug: 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. |
Sex: Female, ages: 18 Years to any
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
| Milestone | Carboplatin + Paclitaxel + Pembrolizumab + Olaparib | Carboplatin + Paclitaxel + Pembrolizumab | Carboplatin + Paclitaxel |
|---|---|---|---|
| Started | 455 | 458 | 454 |
| Treated | 452 | 456 | 454 |
| Completed | 0 | 0 | 0 |
| Not completed | 455 | 458 | 454 |
Time frame: Up to approximately 67 months
| Arm | Deaths | Serious adverse events | Other adverse events |
|---|---|---|---|
| Carboplatin + Paclitaxel + Pembrolizumab + Olaparib | 237/455 (52.1%) | 205/452 (45.4%) | 445/452 (98.5%) |
| Carboplatin + Paclitaxel + Pembrolizumab | 243/458 (53.1%) | 179/456 (39.3%) | 442/456 (96.9%) |
| Carboplatin + Paclitaxel | 229/454 (50.4%) | 122/454 (26.9%) | 445/454 (98.0%) |
| Term | Organ system | Carboplatin + Paclitaxel + Pembrolizumab + Olaparib | Carboplatin + Paclitaxel + Pembrolizumab | Carboplatin + Paclitaxel |
|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | 6/452 | 5/456 | 4/454 |
| Aplasia pure red cell | Blood and lymphatic system disorders | 1/452 | 0/456 | 0/454 |
| Autoimmune haemolytic anaemia | Blood and lymphatic system disorders | 1/452 | 0/456 | 0/454 |
| Bone marrow failure | Blood and lymphatic system disorders | 1/452 | 0/456 | 0/454 |
| Disseminated intravascular coagulation | Blood and lymphatic system disorders | 1/452 | 1/456 | 0/454 |
| Eosinophilia | Blood and lymphatic system disorders | 0/452 | 1/456 | 0/454 |
| Febrile neutropenia | Blood and lymphatic system disorders | 19/452 | 16/456 | 9/454 |
| Leukopenia | Blood and lymphatic system disorders | 3/452 | 0/456 | 1/454 |
| Lymphadenopathy mediastinal | Blood and lymphatic system disorders | 1/452 | 0/456 | 0/454 |
| Neutropenia | Blood and lymphatic system disorders | 5/452 | 3/456 | 3/454 |
| Pancytopenia | Blood and lymphatic system disorders | 1/452 | 0/456 | 0/454 |
| Thrombocytopenia | Blood and lymphatic system disorders | 3/452 | 1/456 | 2/454 |
| Acute coronary syndrome | Cardiac disorders | 1/452 | 0/456 | 0/454 |
| Acute myocardial infarction | Cardiac disorders | 1/452 | 0/456 | 1/454 |
| Angina pectoris | Cardiac disorders | 1/452 | 0/456 | 1/454 |
| Angina unstable | Cardiac disorders | 0/452 | 1/456 | 0/454 |
| Atrial fibrillation | Cardiac disorders | 1/452 | 3/456 | 0/454 |
| Autoimmune myocarditis | Cardiac disorders | 0/452 | 1/456 | 0/454 |
| Bundle branch block left | Cardiac disorders | 1/452 | 0/456 | 0/454 |
| Cardiomyopathy | Cardiac disorders | 0/452 | 0/456 | 1/454 |
| Coronary artery disease | Cardiac disorders | 0/452 | 1/456 | 0/454 |
| Myocardial infarction | Cardiac disorders | 1/452 | 2/456 | 2/454 |
| Myocarditis | Cardiac disorders | 1/452 | 0/456 | 0/454 |
| Ventricular hypokinesia | Cardiac disorders | 0/452 | 1/456 | 0/454 |
| Vertigo | Ear and labyrinth disorders | 1/452 | 1/456 | 0/454 |
| Vertigo positional | Ear and labyrinth disorders | 1/452 | 0/456 | 0/454 |
| Adrenal insufficiency | Endocrine disorders | 4/452 | 4/456 | 0/454 |
| Hyperthyroidism | Endocrine disorders | 1/452 | 0/456 | 0/454 |
| Hypophysitis | Endocrine disorders | 2/452 | 2/456 | 0/454 |
| Hypopituitarism | Endocrine disorders | 0/452 | 2/456 | 0/454 |
| Hypothyroidism | Endocrine disorders | 2/452 | 0/456 | 0/454 |
| Thyroid disorder | Endocrine disorders | 1/452 | 0/456 | 0/454 |
| Thyroiditis | Endocrine disorders | 1/452 | 1/456 | 0/454 |
| Macular hole | Eye disorders | 0/452 | 1/456 | 0/454 |
| Vogt-Koyanagi-Harada disease | Eye disorders | 1/452 | 0/456 | 0/454 |
| Abdominal adhesions | Gastrointestinal disorders | 0/452 | 1/456 | 0/454 |
| Abdominal hernia | Gastrointestinal disorders | 1/452 | 0/456 | 2/454 |
| Abdominal pain | Gastrointestinal disorders | 4/452 | 1/456 | 2/454 |
| Abdominal pain lower | Gastrointestinal disorders | 0/452 | 0/456 | 1/454 |
| Abdominal pain upper | Gastrointestinal disorders | 1/452 | 0/456 | 1/454 |
| Ascites | Gastrointestinal disorders | 1/452 | 4/456 | 2/454 |
| Colitis | Gastrointestinal disorders | 4/452 | 6/456 | 2/454 |
| Colonic fistula | Gastrointestinal disorders | 0/452 | 1/456 | 0/454 |
| Constipation | Gastrointestinal disorders | 1/452 | 3/456 | 0/454 |
| Diarrhoea | Gastrointestinal disorders | 4/452 | 2/456 | 1/454 |
| Dysphagia | Gastrointestinal disorders | 1/452 | 0/456 | 0/454 |
| Enteritis | Gastrointestinal disorders | 2/452 | 0/456 | 1/454 |
| Enterocolitis | Gastrointestinal disorders | 2/452 | 0/456 | 2/454 |
| Enterocutaneous fistula | Gastrointestinal disorders | 0/452 | 2/456 | 0/454 |
| Faecaloma | Gastrointestinal disorders | 1/452 | 5/456 | 0/454 |
| Flatulence | Gastrointestinal disorders | 1/452 | 0/456 | 0/454 |
| Gastric ulcer | Gastrointestinal disorders | 0/452 | 1/456 | 1/454 |
| Gastritis | Gastrointestinal disorders | 2/452 | 0/456 | 0/454 |
| Gastrointestinal haemorrhage | Gastrointestinal disorders | 0/452 | 1/456 | 1/454 |
| Haemorrhoids | Gastrointestinal disorders | 1/452 | 1/456 | 0/454 |
| Hernial eventration | Gastrointestinal disorders | 3/452 | 0/456 | 0/454 |
| Ileal perforation | Gastrointestinal disorders | 1/452 | 0/456 | 0/454 |
| Ileus | Gastrointestinal disorders | 6/452 | 6/456 | 4/454 |
| Impaired gastric emptying | Gastrointestinal disorders | 0/452 | 2/456 | 0/454 |
| Intestinal obstruction | Gastrointestinal disorders | 8/452 | 9/456 | 6/454 |
279 more terms not shown.
| Term | Organ system | Carboplatin + Paclitaxel + Pembrolizumab + Olaparib | Carboplatin + Paclitaxel + Pembrolizumab | Carboplatin + Paclitaxel |
|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | 270/452 | 212/456 | 205/454 |
| Leukopenia | Blood and lymphatic system disorders | 90/452 | 60/456 | 60/454 |
| Neutropenia | Blood and lymphatic system disorders | 170/452 | 138/456 | 147/454 |
| Thrombocytopenia | Blood and lymphatic system disorders | 89/452 | 73/456 | 72/454 |
| Hyperthyroidism | Endocrine disorders | 33/452 | 44/456 | 23/454 |
| Hypothyroidism | Endocrine disorders | 89/452 | 93/456 | 42/454 |
| Abdominal distension | Gastrointestinal disorders | 26/452 | 26/456 | 24/454 |
| Abdominal pain | Gastrointestinal disorders | 91/452 | 90/456 | 102/454 |
| Abdominal pain upper | Gastrointestinal disorders | 50/452 | 54/456 | 42/454 |
| Constipation | Gastrointestinal disorders | 121/452 | 122/456 | 104/454 |
| Diarrhoea | Gastrointestinal disorders | 121/452 | 138/456 | 94/454 |
| Dyspepsia | Gastrointestinal disorders | 40/452 | 22/456 | 28/454 |
| Nausea | Gastrointestinal disorders | 227/452 | 187/456 | 150/454 |
| Stomatitis | Gastrointestinal disorders | 46/452 | 35/456 | 30/454 |
| Vomiting | Gastrointestinal disorders | 114/452 | 81/456 | 70/454 |
| Asthenia | General disorders | 116/452 | 97/456 | 70/454 |
| Fatigue | General disorders | 120/452 | 115/456 | 85/454 |
| Mucosal inflammation | General disorders | 33/452 | 23/456 | 17/454 |
| Oedema peripheral | General disorders | 35/452 | 28/456 | 36/454 |
| Pyrexia | General disorders | 66/452 | 50/456 | 34/454 |
| COVID-19 | Infections and infestations | 65/452 | 53/456 | 53/454 |
| Cystitis | Infections and infestations | 24/452 | 15/456 | 14/454 |
| Nasopharyngitis | Infections and infestations | 21/452 | 26/456 | 30/454 |
| Urinary tract infection | Infections and infestations | 91/452 | 79/456 | 85/454 |
| Alanine aminotransferase increased | Investigations | 74/452 | 65/456 | 71/454 |
| Aspartate aminotransferase increased | Investigations | 68/452 | 64/456 | 59/454 |
| Blood alkaline phosphatase increased | Investigations | 26/452 | 33/456 | 22/454 |
| Blood creatinine increased | Investigations | 46/452 | 21/456 | 22/454 |
| Lymphocyte count decreased | Investigations | 28/452 | 19/456 | 7/454 |
| Neutrophil count decreased | Investigations | 104/452 | 96/456 | 102/454 |
| Platelet count decreased | Investigations | 79/452 | 65/456 | 58/454 |
| Weight decreased | Investigations | 51/452 | 37/456 | 28/454 |
| Weight increased | Investigations | 12/452 | 23/456 | 18/454 |
| White blood cell count decreased | Investigations | 88/452 | 63/456 | 80/454 |
| Decreased appetite | Metabolism and nutrition disorders | 83/452 | 69/456 | 52/454 |
| Hyperglycaemia | Metabolism and nutrition disorders | 23/452 | 18/456 | 20/454 |
| Hypokalaemia | Metabolism and nutrition disorders | 43/452 | 44/456 | 21/454 |
| Hypomagnesaemia | Metabolism and nutrition disorders | 49/452 | 53/456 | 58/454 |
| Hyponatraemia | Metabolism and nutrition disorders | 24/452 | 23/456 | 20/454 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 136/452 | 142/456 | 139/454 |
| Back pain | Musculoskeletal and connective tissue disorders | 63/452 | 48/456 | 67/454 |
| Bone pain | Musculoskeletal and connective tissue disorders | 20/452 | 13/456 | 23/454 |
| Myalgia | Musculoskeletal and connective tissue disorders | 72/452 | 82/456 | 75/454 |
| Pain in extremity | Musculoskeletal and connective tissue disorders | 38/452 | 61/456 | 45/454 |
| Dizziness | Nervous system disorders | 52/452 | 41/456 | 43/454 |
| Dysgeusia | Nervous system disorders | 41/452 | 35/456 | 22/454 |
| Headache | Nervous system disorders | 87/452 | 67/456 | 77/454 |
| Hypoaesthesia | Nervous system disorders | 23/452 | 18/456 | 22/454 |
| Neuropathy peripheral | Nervous system disorders | 85/452 | 91/456 | 83/454 |
| Paraesthesia | Nervous system disorders | 32/452 | 32/456 | 35/454 |
| Peripheral sensory neuropathy | Nervous system disorders | 54/452 | 68/456 | 56/454 |
| Anxiety | Psychiatric disorders | 19/452 | 21/456 | 23/454 |
| Insomnia | Psychiatric disorders | 35/452 | 38/456 | 45/454 |
| Dysuria | Renal and urinary disorders | 29/452 | 11/456 | 17/454 |
| Proteinuria | Renal and urinary disorders | 33/452 | 36/456 | 37/454 |
| Cough | Respiratory, thoracic and mediastinal disorders | 46/452 | 46/456 | 41/454 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 55/452 | 51/456 | 41/454 |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | 38/452 | 38/456 | 47/454 |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | 30/452 | 17/456 | 26/454 |
| Alopecia | Skin and subcutaneous tissue disorders | 123/452 | 114/456 | 131/454 |
4 more terms not shown.
| Facility | City | Country | Status |
|---|---|---|---|
| University of Alabama at Birmingham (UAB) ( Site 0036) | Birmingham, Alabama | United States | |
| 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 Oncology Clinical Trials-Roseville ( Site 0084) | Roseville, California | United States | |
| Kaiser Permanente Oncology Clinical Trials-Sacramento ( Site 0083) | Sacramento, California | United States | |
| Kaiser Permanente Oncology Clinical Trial - San Francisco ( Site 0078) | San Francisco, California | United States | |
| Kaiser Permanente Oncology Clinical Trial - Santa Clara ( Site 0079) | Santa Clara, California | United States | |
| Kaiser Permanente N. CA Regional Oncology Clinical Trials ( Site 0008) | Vallejo, California | United States | |
| Kaiser Permanente Oncology Clinical Trial - Walnut Creek ( Site 0080) | Walnut Creek, California | United States | |
| Smilow Cancer Center at Yale-New Haven ( Site 0057) | New Haven, Connecticut | United States | |
| Sarasota Memorial Hospital ( Site 0023) | Sarasota, Florida | United States | |
| Emory School of Medicine ( Site 0053) | Atlanta, Georgia | United States | |
| Northeast Georgia Medical Center ( Site 0029) | Gainesville, Georgia | United States | |
| Memorial Health University Medical Center ( Site 0011) | Savannah, Georgia | United States | |
| Rush University Medical Center ( Site 0019) | Chicago, Illinois | United States | |
| University of Chicago ( Site 0049) | Chicago, Illinois | United States | |
| Dr. Sudarshan K. Sharma, LTD ( Site 0061) | Hinsdale, Illinois | United States | |
| Saint Vincent Hospital and Health Center ( Site 0012) | Indianapolis, Indiana | United States | |
| University of Iowa Hospital and Clinics ( Site 0005) | Iowa City, Iowa | United States | |
| University of Kentucky ( Site 0045) | Lexington, Kentucky | United States | |
| Weinberg Cancer Institute at Franklin Square ( Site 0035) | Baltimore, Maryland | United States | |
| Saint Dominic - Jackson Memorial Hospital ( Site 0072) | Jackson, Mississippi | United States | |
| Washington University - School of Medicine ( Site 0062) | St Louis, Missouri | United States | |
| Nebraska Methodist Hospital ( Site 0063) | Omaha, Nebraska | United States | |
| Dartmouth Hitchcock Medical Center ( Site 0024) | Lebanon, New Hampshire | United States | |
| MD Anderson Cancer Center at Cooper ( Site 0067) | Camden, New Jersey | United States | |
| Holy Name Medical Center ( Site 0037) | Teaneck, New Jersey | United States | |
| Northwell Health- Monter Cancer Center ( Site 0075) | Lake Success, New York | United States | |
| Sanford Roger Maris Cancer Center ( Site 0082) | Fargo, North Dakota | United States | |
| Miami Valley Hospital [Dayton, OH] ( Site 0073) | Centerville, Ohio | United States | |
| Oncology/Hematology Care Clinical Trials, LLC ( Site 8001) | Cincinnati, Ohio | United States | |
| The Bing Cancer Center ( Site 0044) | Columbus, Ohio | United States | |
| OSU Wexner Medical Center ( Site 0076) | Hilliard, Ohio | United States | |
| Women and Infants Hospital [Providence, RI] ( Site 0039) | Providence, Rhode Island | United States | |
| Sanford Gynecology Oncology ( Site 0004) | Sioux Falls, South Dakota | United States | |
| Texas Oncology, P.A. - Bedford ( Site 8005) | Bedford, Texas | United States | |
| Texas Oncology-Dallas Presbyterian Hospital ( Site 8004) | Dallas, Texas | United States | |
| Parkland Hospital ( Site 0081) | Dallas, Texas | United States | |
| UT Southwestern Medical Center ( Site 0046) | Dallas, Texas | United States | |
| Texas Oncology, P.A. Texas Oncology-Tyler ( Site 8006) | Tyler, Texas | United States | |
| Virginia Cancer Specialists, PC ( Site 8003) | Gainesville, Virginia | United States | |
| MEDICAL COLLEGE OF WISCONSIN ( Site 0064) | Milwaukee, Wisconsin | United States | |
| St George Hospital ( Site 2207) | Kogarah, New South Wales | Australia | |
| Cairns and Hinterland Hospital and Health Service ( Site 2201) | Cairns, Queensland | Australia | |
| Ballarat Health Services ( Site 2202) | Ballarat, Victoria | Australia | |
| Monash Health ( Site 2204) | Clayton, Victoria | Australia | |
| Sunshine Hospital. ( Site 2205) | St Albans, Victoria | Australia | |
| Imelda Ziekenhuis Bonheiden ( Site 0301) | Bonheiden, Antwerpen | Belgium | |
| UZ Leuven Campus Gasthuisberg ( Site 0306) | Leuven, Antwerpen | Belgium | |
| Cliniques Universitaires Saint-Luc ( Site 0312) | Brussels, Bruxelles-Capitale, Region de | Belgium | |
| Grand Hopital de Charleroi ( Site 0302) | Charleroi, Hainaut | Belgium | |
| CHU de Liege ( Site 0310) | Liège, Liege | Belgium | |
| Jessa Ziekenhuis ( Site 0309) | Hasselt, Limburg | Belgium | |
| Centre Hospitalier de l'Ardenne ( Site 0303) | Libramont, Luxembourg | Belgium | |
| AZ Maria Middelares Gent ( Site 0300) | Ghent, Oost-Vlaanderen | Belgium | |
| UZ Gent ( Site 0307) | Ghent, Oost-Vlaanderen | Belgium | |
| Instituto do Cancer do Ceara ( Site 2707) | Fortaleza, Ceará | Brazil | |
| Hospital Araujo Jorge Associacao de Combate ao Cancer de Goias ( Site 2708) | Goiânia, Goiás | Brazil | |
| Hospital Erasto Gaertner ( Site 2716) | Curitiba, Paraná | Brazil | |
| Hospital de Caridade de Ijui ( Site 2712) | Ijuí, Rio Grande do Sul | Brazil | |
| Hospital Bruno Born ( Site 2704) | Lajeado, Rio Grande do Sul | 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 | |
| Instituto do Cancer do Estado de Sao Paulo - ICESP ( Site 2714) | São Paulo | Brazil | |
| Clinica de Pesquisas e Ctro de Estudos Onc. Ginecol. e Mamaria Ltda ( Site 2706) | São Paulo | Brazil | |
| Real e Benemerita Associacao Portuguesa de Beneficencia ( Site 2710) | São Paulo | Brazil | |
| Tom Baker Cancer Centre ( Site 0200) | Calgary, Alberta | Canada | |
| Kingston Health Sciences Centre ( Site 0207) | Kingston, Ontario | Canada | |
| The Credit Valley Hospital ( Site 0206) | Mississauga, Ontario | Canada | |
| Princess Margaret Hospital.. ( Site 0202) | Toronto, Ontario | Canada | |
| CIUSSS du Saguenay-Lac-St-Jean ( Site 0218) | Chicoutimi, Quebec | Canada | |
| CIUSSS de l Est de L Ile de Montreal - Hopital Maisonneuve-Rosemont ( Site 0219) | Montreal, 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 | |
| Centro Investigación del Cáncer James Lind ( Site 2810) | Temuco, Araucania | Chile | |
| Centro de Investigacion y desarrollo Oncologico SpA - CIDO SpA ( Site 2808) | Temuco, Araucania | Chile | |
| Fundacion Arturo Lopez Perez FALP ( Site 2800) | Santiago, Region M. de Santiago | Chile | |
| Sociedad Oncovida S.A. ( Site 2807) | Santiago, Region M. de Santiago | Chile | |
| Iram Cancer Research ( Site 2809) | Santiago, Region M. de Santiago | Chile | |
| Pontificia Universidad Catolica de Chile ( Site 2805) | Santiago, Region M. de Santiago | Chile | |
| Oncocentro ( Site 2801) | Viña del Mar, Valparaiso | Chile | |
| Centro Oncologico Antofagasta ( Site 2804) | Antofagasta | Chile | |
| Biomelab S A S ( Site 2900) | Barranquilla, Atlántico | Colombia | |
| Instituto Nacional de Cancerologia E.S.E ( Site 2910) | Bogotá, Bogota D.C. | Colombia | |
| Clinica Colsanitas S.A. Sede Clinica Universitaria Colombia ( Site 2912) | Bogotá, Bogota D.C. | Colombia | |
| Sociedad de Oncología Y Hematología del Cesar S.A.S. ( Site 2913) | Valledupar, Cesar Department | Colombia | |
| Oncomedica S.A. ( Site 2911) | Montería, Departamento de Córdoba | Colombia | |
| Centro Medico Imbanaco de Cali S.A ( Site 2909) | Cali, Valle del Cauca Department | Colombia | |
| Hemato Oncologos S.A. ( Site 2906) | Cali, Valle del Cauca Department | Colombia | |
| Fakultni nemocnice Brno ( Site 0404) | Brno, Brno-mesto | Czechia | |
| Fakultni nemocnice Ostrava ( Site 0403) | Ostrava-Poruba, Moravian-Silesian Region | Czechia | |
| Vseobecna fakultni nemocnice v Praze ( Site 0400) | Prague, Praha, Hlavni Mesto | Czechia | |
| Nemocnice Na Bulovce ( Site 0401) | Prague, Praha, Hlavni Mesto | Czechia | |
| Fakultni nemocnice Olomouc ( Site 0402) | Olomouc | Czechia | |
| Hopital Prive Jean Mermoz ( Site 0607) | Lyon, Auvergne | France | |
| Centre Paul Strauss ( Site 0615) | Strasbourg, Bas-Rhin | France | |
| Hopital de la Timone ( Site 0617) | Marseille, Bouches-du-Rhone | France | |
| CHU de Brest -Site Hopital Morvan ( Site 0616) | Brest, Brittany Region | France | |
| Institut de Cancerologie du Gard - CHU Caremeau ( Site 0610) | Nîmes, Gard | France |
127 more sites not listed.
NIH grants: 2018