Efficacy and Safety of Olaparib (MK-7339) With or Without Bevacizumab Compared to Bevacizumab With a Fluoropyrimidine in Unresectable or Metastatic Colorectal Cancer (CRC) (MK-7339-003/LYNK-003)

Phase 3

Completed

Conditions: Metastatic Colorectal Cancer

Interventions: Drug: Olaparib
Drug: 5-FU
Drug: Bevacizumab
Drug: Capecitabine
Drug: Leucovorin/ levoleucovorin

Registration Number: NCT04456699

Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary: This is an efficacy and safety study of olaparib alone or in combination with bevacizumab being compared to bevacizumab with a fluoropyrimidine in participants with unresectable or metastatic colorectal cancer who have not progressed following first-line induction. The primary hypotheses are: Olaparib + Bevacizumab is superior to a fluoropyrimidine + Bevacizumab with respect to progression-free survival (PFS) using Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1) as assessed by blinded independent central review (BICR); Olaparib is superior to a fluoropyrimidine + Bevacizumab with respect to PFS using RECIST 1.1 as assessed by BICR. As of amendment 5 study enrollment is being discontinued and study participants randomized to one of the two experimental arms (olaparib plus bevacizumab or olaparib monotherapy) must discontinue study intervention. Participants who are still on study treatment will no longer have tumor response assessments by BICR.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 335

Inclusion Criteria

Has a histologically-confirmed metastatic or unresectable (Stage IV as defined by American Joint Committee on Cancer (AJCC eighth edition) colorectal adenocarcinoma (National Comprehensive Cancer Network [NCCN] 2018).
Has not progressed (ie, achieved a stable disease [SD], partial response [PR], or complete response [CR]) after a first-line induction course of at least 6 cycles of folinic acid/fluorouracil/oxaliplatin (FOLFOX) + bevacizumab or 4 cycles of capecitabine and oxaliplatin (CAPOX) + bevacizumab as first-line therapy.
- Participants must not have received an investigational agent during their induction course.
- Determination of best overall response (SD/PR/CR) will be made by the investigator.
- Non-Progressive Disease (PD) will be verified by BICR prior to randomization based on the images submitted to imaging contract research organization (iCRO) as described in inclusion criterion 4.
- "First-line therapy" is defined as the first systemic chemotherapy regimen given for the diagnosis of unresectable or metastatic colorectal cancer (CRC). Participants may have received prior adjuvant/neoadjuvant chemotherapy for CRC, as long as it was completed at least 6 months prior to initiation of first-line CAPOX + bevacizumab or FOLFOX + bevacizumab induction treatment.
Has experienced unacceptable toxicity to oxaliplatin that, in the opinion of the treating physician, requires/required the discontinuation of oxaliplatin. Note: As an example, unacceptable toxicity may include (but is not limited to) severe or prolonged neurotoxicity.

• Participants must be randomized within a minimum of 2 weeks and a maximum of 6 weeks after their last dose of CAPOX + bevacizumab or FOLFOX + bevacizumab (last dose is the day of the last infusion that contained oxaliplatin).
Has provided to the iCRO 1 set of baseline radiographic images taken before or during the CAPOX + bevacizumab or FOLFOX + bevacizumab induction period and at least 42 days prior to the imaging performed during Screening. Tumor imaging at Screening must be performed within 28 days prior to the date of randomization.
Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within 10 days prior to randomization.

Exclusion Criteria

Has known hypersensitivity to the components and/or excipients in bevacizumab, 5-FU, capecitabine, or olaparib.
Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable (ie, without evidence of progression for at least 28 days by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid intervention for at least 14 days prior to first dose of study intervention.
Has an active infection requiring systemic therapy.
Has a known history of human immunodeficiency virus (HIV) infection. No HIV testing is required unless mandated by local health authority.
Has a known history of or is positive for hepatitis B surface antigen (HBsAg reactive) or hepatitis C ribonucleic acid (HCV RNA [qualitative]) is detected). Note: No testing for hepatitis B and hepatitis C is required unless mandated by local health authority.
Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study.
Has myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) or with features suggestive of MDS/AML.
Has hemoptysis or hematemesis within 28 days prior to randomization.
Has evidence of bleeding diathesis or significant coagulopathy (in the absence of anticoagulation).
Has clinically significant bleeding within 28 days prior to randomization.
Is considered a poor medical risk due to a serious, uncontrolled medical disorder, nonmalignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on high-resolution computed tomography (HRCT) scan or any psychiatric disorder that prohibits obtaining informed consent.
Has 1 or more conditions that, in the opinion of the treating physician, make the participant ineligible for treatment with bevacizumab. These conditions may include:
- Uncontrolled hypertension (systolic blood pressure [SBP] >150 mm Hg or diastolic blood pressure [DBP] >100 mm Hg) or a history of hypertensive crisis or hypertensive encephalopathy
- Arterial thromboembolic events (eg, myocardial infarction, cerebral infarction)
- History of nephrotic syndrome or moderate proteinuria
- History of gastrointestinal perforation
- History of non-gastrointestinal fistula formation
- History of possible reversible encephalopathy syndrome (RPLS)
Has received prior systemic anticancer therapy (other than CAPOX + bevacizumab or FOLFOX + bevacizumab induction) including investigational agents within 28 days prior to randomization. Note: Participants must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Participants with persistent alopecia or Grade ≤3 neuropathy are eligible.
Has received prior therapy with olaparib or with any other polyadenosine 5'-diphosphoribose polymerase (PARP) inhibitor.
Is currently receiving either strong (eg, 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 3A4 (CYP3A4) that cannot be discontinued for the duration of the study. The required washout period prior to randomization is 2 weeks.
Is currently receiving either strong (phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate (eg. bosentan, efavirenz, modafinil) inducers of CYP3A4 that cannot be discontinued for the duration of the study. The required washout period prior to randomization is 5 weeks for phenobarbital and 3 weeks for other agents.
Has undergone major surgery within 2 weeks of randomization or has not recovered adequately from toxicities and/or complications from any major surgery prior to randomization.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Bevacizumab + chemotherapy	Leucovorin/ levoleucovorin	Participants will receive investigator's choice of either bevacizumab (7.5 mg/kg IV once every three weeks (Q3W)) + capecitabine (1000 mg/m\^2 BID for 14 days, then 7 days off, Q3W) or bevacizumab (5 mg/kg IV Q2W) + 5-FU (2400 mg/m2 IV over 46 to 48 hours Q2W; bolus 5-FU (400 mg/m2) can be added prior to infusional 5-FU, per local standards and at the investigator's discretion). Leucovorin or levoleucovorin 400 mg/m\^2 (leucovorin) or 200 mg/m\^2 (levoleucovorin) Q2W IV infusion may be added per investigator's discretion. Treatment will continue until progressive disease or end of study.
Olaparib + bevacizumab	Olaparib	Participants will receive olaparib (300 mg twice daily \[BID\] oral) + Bevacizumab (5 mg/kg intravenous \[IV\] once every 2 weeks \[Q2W\]) until progressive disease or end of study.
Olaparib + bevacizumab	Bevacizumab	Participants will receive olaparib (300 mg twice daily \[BID\] oral) + Bevacizumab (5 mg/kg intravenous \[IV\] once every 2 weeks \[Q2W\]) until progressive disease or end of study.
Olaparib	Olaparib	Participants will receive olaparib (300 mg BID) oral, until progressive disease or end of study.
Bevacizumab + chemotherapy	5-FU	Participants will receive investigator's choice of either bevacizumab (7.5 mg/kg IV once every three weeks (Q3W)) + capecitabine (1000 mg/m\^2 BID for 14 days, then 7 days off, Q3W) or bevacizumab (5 mg/kg IV Q2W) + 5-FU (2400 mg/m2 IV over 46 to 48 hours Q2W; bolus 5-FU (400 mg/m2) can be added prior to infusional 5-FU, per local standards and at the investigator's discretion). Leucovorin or levoleucovorin 400 mg/m\^2 (leucovorin) or 200 mg/m\^2 (levoleucovorin) Q2W IV infusion may be added per investigator's discretion. Treatment will continue until progressive disease or end of study.
Bevacizumab + chemotherapy	Capecitabine	Participants will receive investigator's choice of either bevacizumab (7.5 mg/kg IV once every three weeks (Q3W)) + capecitabine (1000 mg/m\^2 BID for 14 days, then 7 days off, Q3W) or bevacizumab (5 mg/kg IV Q2W) + 5-FU (2400 mg/m2 IV over 46 to 48 hours Q2W; bolus 5-FU (400 mg/m2) can be added prior to infusional 5-FU, per local standards and at the investigator's discretion). Leucovorin or levoleucovorin 400 mg/m\^2 (leucovorin) or 200 mg/m\^2 (levoleucovorin) Q2W IV infusion may be added per investigator's discretion. Treatment will continue until progressive disease or end of study.
Bevacizumab + chemotherapy	Bevacizumab	Participants will receive investigator's choice of either bevacizumab (7.5 mg/kg IV once every three weeks (Q3W)) + capecitabine (1000 mg/m\^2 BID for 14 days, then 7 days off, Q3W) or bevacizumab (5 mg/kg IV Q2W) + 5-FU (2400 mg/m2 IV over 46 to 48 hours Q2W; bolus 5-FU (400 mg/m2) can be added prior to infusional 5-FU, per local standards and at the investigator's discretion). Leucovorin or levoleucovorin 400 mg/m\^2 (leucovorin) or 200 mg/m\^2 (levoleucovorin) Q2W IV infusion may be added per investigator's discretion. Treatment will continue until progressive disease or end of study.

Primary Outcome Measures

Name	Time	Method
Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1 as Assessed by Blinded Independent Central Review (BICR)	Up to approximately 30 months	PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD was 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 new lesions was also considered PD. PFS using RECIST 1.1 as assessed by BICR is presented.

Secondary Outcome Measures

Name	Time	Method
Overall Survival (OS)	Up to approximately 30 months	OS was defined as the time from randomization to death due to any cause. The OS is presented.
Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BICR	Up to approximately 30 months	ORR was defined as the percentage of participants who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ.
Number of Participants With One or More Adverse Events (AE)	Up to approximately 30 months	An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who experienced at least one AE was reported for each arm.
Number of Participants Discontinuing Study Intervention Due to an AE	Up to approximately 30 months	An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who discontinued study intervention due to an AE was reported for each arm.
Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR	Up to approximately 30 months	For participants who demonstrate a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. DOR is defined as the time from first documented evidence of a CR or PR until progressive disease (PD) or death. DOR for participants who had not progressed or died at the time of analysis will be censored at the date of their last tumor assessment. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions as well as an absolute increase of at least a 5 mm in the sum of diameters. The appearance of one or more new lesions is also considered PD. DOR assessments will be based on BICR with confirmation. The DOR as assessed using RECIST 1.1 for all participants who experience a confirmed CR or PR will be presented.

Trial Locations

Locations (129): Hospital Universitario Central de Asturias ( Site 1153)
🇪🇸
Oviedo, Asturias, Spain
Providence Portland Medical Center ( Site 1400)
🇺🇸
Portland, Oregon, United States
Oregon Health & Science University ( Site 1411)
🇺🇸
Portland, Oregon, United States
Chiba Cancer Center ( Site 0656)
🇯🇵
Chiba, Japan
Riga East Clinical University Hospital ( Site 1501)
🇱🇻
Riga, Latvia
Nacionalinis Vezio Institutas ( Site 1527)
🇱🇹
Vilnius, Lithuania
National Medical and Surgical Center n.a. N.I.Pirogov ( Site 1126)
🇷🇺
Moscow, Moskva, Russian Federation
Inonu Universitesi Medical Fakultesi ( Site 1207)
🇹🇷
Malatya, Adana, Turkey
N.N. Blokhin NMRCO ( Site 1106)
🇷🇺
Moscow, Moskva, Russian Federation
Sandton Oncology Medical Group PTY LTD ( Site 0900)
🇿🇦
Sandton, Gauteng, South Africa
Hospital Vall D Hebron ( Site 1151)
🇪🇸
Barcelona, Spain
Hospital 12 de Octubre de Madrid ( Site 1150)
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Madrid, Spain
Necmettin Erbakan Universitesi Meram Tip Fakultesi ( Site 1203)
🇹🇷
Konya, Turkey
Medical center Medikal Plaza of Ecodnipro LLC ( Site 1317)
🇺🇦
Dnipro, Dnipropetrovska Oblast, Ukraine
Medical Center of Yuriy Spizhenko LLC.-Clinical Trial ( Site 1319)
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Kapitanivka Village, Kyivska Oblast, Ukraine
Hospital Universitario Gregorio Maranon ( Site 1152)
🇪🇸
Madrid, Spain
Samsung Medical Center ( Site 0954)
🇰🇷
Seoul, Korea, Republic of
St Joseph Heritage Healthcare-Oncology ( Site 1383)
🇺🇸
Fullerton, California, United States
Providence Saint Joseph Medical Center, Disney Family Cancer ( Site 1392)
🇺🇸
Burbank, California, United States
Poudre Valley Health System ( Site 1402)
🇺🇸
Fort Collins, Colorado, United States
UC Health Memorial Hospital ( Site 1401)
🇺🇸
Colorado Springs, Colorado, United States
University of Chicago ( Site 1357)
🇺🇸
Chicago, Illinois, United States
University Cancer & Blood Center, LLC ( Site 1381)
🇺🇸
Athens, Georgia, United States
Illinois Cancer Care, PC ( Site 1352)
🇺🇸
Peoria, Illinois, United States
James Graham Brown Cancer Center ( Site 1393)
🇺🇸
Louisville, Kentucky, United States
Washington University in St. Louis ( Site 1384)
🇺🇸
Saint Louis, Missouri, United States
CHI Health St. Francis ( Site 1406)
🇺🇸
Grand Island, Nebraska, United States
Allegheny Singer Research Institute ( Site 1364)
🇺🇸
Pittsburgh, Pennsylvania, United States
West Cancer Center - East Campus ( Site 1396)
🇺🇸
Germantown, Tennessee, United States
Vanderbilt University Medical Center ( Site 1362)
🇺🇸
Nashville, Tennessee, United States
Baylor Scott & White Medical Center - Temple ( Site 1397)
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Temple, Texas, United States
Blue Ridge Cancer Care ( Site 1374)
🇺🇸
Roanoke, Virginia, United States
Royal Brisbane and Women s Hospital ( Site 0054)
🇦🇺
Herston, Queensland, Australia
St George Hospital ( Site 0052)
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Kogarah, New South Wales, Australia
Liverpool Hospital ( Site 0055)
🇦🇺
Liverpool, New South Wales, Australia
Queen Elizabeth Hospital ( Site 0053)
🇦🇺
Woodville South, South Australia, Australia
Peninsula Health Frankston Hospital ( Site 0056)
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Frankston, Victoria, Australia
AZ Klina ( Site 0106)
🇧🇪
Brasschaat, Antwerpen, Belgium
UZ Antwerpen ( Site 0108)
🇧🇪
Edegem, Antwerpen, Belgium
UCL Saint Luc ( Site 0100)
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Brussels, Bruxelles-Capitale, Region De, Belgium
Dr. Everett Chalmers Regional Hospital ( Site 0204)
🇨🇦
Fredericton, New Brunswick, Canada
Princess Margaret Cancer Centre ( Site 0209)
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Toronto, Ontario, Canada
McGill University Health Centre ( Site 0207)
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Montreal, Quebec, Canada
Sociedad Oncovida S.A. ( Site 0250)
🇨🇱
Santiago, Region M. De Santiago, Chile
Centro Investigación del Cáncer James Lind ( Site 0251)
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Temuco, Araucania, Chile
Clínica San Carlos de Apoquindo Red Salud UC Christus ( Site 0252)
🇨🇱
Santiago, Region M. De Santiago, Chile
Instituto Nacional de Cancerologia E.S.E ( Site 0362)
🇨🇴
Bogota, Distrito Capital De Bogota, Colombia
Sociedad de Oncología Y Hematología del Cesar S.A.S. ( Site 0353)
🇨🇴
Valledupar, Cesar, Colombia
Administradora Country SA - Clinica del Country ( Site 0350)
🇨🇴
Bogota, Distrito Capital De Bogota, Colombia
Oncomedica S.A. ( Site 0352)
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Monteria, Cordoba, Colombia
Fundacion Cardiovascular de Colombia ( Site 0360)
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Bucaramanga, Santander, Colombia
Oncologos del Occidente ( Site 0364)
🇨🇴
Pereira, Risaralda, Colombia
Centre Leon Berard ( Site 0459)
🇫🇷
Lyon, Rhone-Alpes, France
Hemato Oncologos S.A. ( Site 0355)
🇨🇴
Cali, Valle Del Cauca, Colombia
C.H.U. de Strasbourg Hopital de Hautepierre ( Site 0464)
🇫🇷
Strasbourg, Bas-Rhin, France
Institut de Cancerologie de l Ouest Centre Rene Gauducheau ( Site 0455)
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Saint-Herblain, Bretagne, France
CHU Jean Minjoz ( Site 0450)
🇫🇷
Besancon, Doubs, France
CHU Bordeaux Haut-Leveque ( Site 0457)
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Pessac Cedex, Gironde, France
CHU Saint Eloi ( Site 0467)
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Montpellier, Herault, France
St. Josef und St. Elisabeth Hospital gGmbH-Hematology, oncology and palliative medicine ( Site 0503)
🇩🇪
Bochum, Nordrhein-Westfalen, Germany
Hopital Europeen Georges Pompidou ( Site 0452)
🇫🇷
Paris, France
Charité Universitaetsmedizin Berlin - Campus Mitte ( Site 0504)
🇩🇪
Berlin, Germany
Universitaetsklinikum Ulm ( Site 0500)
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Ulm, Baden-Wurttemberg, Germany
Bekes Megyei Kozponti Korhaz - Pandy Kalman Tagkorhaza ( Site 1432)
🇭🇺
Gyula, Bekes, Hungary
Facharztzentrum Eppendorf ( Site 0501)
🇩🇪
Hamburg, Germany
Borsod-Abaúj-Zemplén Megyei Központi Kórház és Egyetemi Okta-Klinikai Onkológiai és Sugárterápiás Ce
🇭🇺
Miskolc, Borsod-Abauj-Zemplen, Hungary
Debreceni Egyetem Klinikai Kozpont ( Site 1426)
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Debrecen, Hajdu-Bihar, Hungary
Jasz Nagykun Szolnok Megyei Hetenyi Geza Korhaz Rendelointezet ( Site 1427)
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Szolnok, Jasz-Nagykun-Szolnok, Hungary
Zala Megyei Szent Rafael Korhaz ( Site 1429)
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Zalaegerszeg, Zala, Hungary
Orszagos Onkologiai Intezet ( Site 1431)
🇭🇺
Budapest, Hungary
Aichi Cancer Center Hospital ( Site 0658)
🇯🇵
Nagoya, Aichi, Japan
National Cancer Center Hospital East ( Site 0650)
🇯🇵
Kashiwa, Chiba, Japan
National Hospital Organization Shikoku Cancer Center ( Site 0652)
🇯🇵
Matsuyama, Ehime, Japan
Saitama Cancer Center ( Site 0653)
🇯🇵
Kitaadachi-gun, Saitama, Japan
Shizuoka Cancer Center Hospital and Research Institute ( Site 0655)
🇯🇵
Sunto-gun, Shizuoka, Japan
National Hospital Organization Kyushu Cancer Center ( Site 0654)
🇯🇵
Fukuoka, Japan
National Cancer Center Hospital ( Site 0651)
🇯🇵
Tokyo, Japan
The Cancer Institute Hospital of JFCR ( Site 0659)
🇯🇵
Tokyo, Japan
Asan Medical Center ( Site 0952)
🇰🇷
Songpagu, Seoul, Korea, Republic of
Kyungpook National University Chilgok Hospital ( Site 0956)
🇰🇷
Daegu, Taegu-Kwangyokshi, Korea, Republic of
Korea University Anam Hospital ( Site 0955)
🇰🇷
Seoul, Korea, Republic of
Seoul National University Hospital ( Site 0950)
🇰🇷
Seoul, Korea, Republic of
Severance Hospital Yonsei University Health System ( Site 0951)
🇰🇷
Seoul, Korea, Republic of
Moncton Hospital - Horizon Health Network ( Site 0201)
🇨🇦
Moncton, New Brunswick, Canada
The Catholic University of Korea St. Mary s Hospital ( Site 0953)
🇰🇷
Seoul, Korea, Republic of
UZ Gasthuisberg ( Site 0102)
🇧🇪
Leuven, Vlaams-Brabant, Belgium
AZ Groeninge ( Site 0105)
🇧🇪
Kortrijk, West-Vlaanderen, Belgium
St. Vincent Frontier Cancer Center-Research ( Site 1414)
🇺🇸
Billings, Montana, United States
Imelda vzw ( Site 0110)
🇧🇪
Bonheiden, Antwerpen, Belgium
LSMUL Kauno Klinikos ( Site 1528)
🇱🇹
Kaunas, Lithuania
Hattiesburg Clinic Hematology/Oncology ( Site 1418)
🇺🇸
Hattiesburg, Mississippi, United States
OLV Ziekenhuis ( Site 0109)
🇧🇪
Aalst, Oost-Vlaanderen, Belgium
Monash Health ( Site 0050)
🇦🇺
Clayton, Victoria, Australia
Cancer Partners of Nebraska ( Site 1353)
🇺🇸
Lincoln, Nebraska, United States
New England Cancer Specialists ( Site 1422)
🇺🇸
Scarborough, Maine, United States
CIUSSS de l Estrie - CHUS - Centre Hosp. Univ. Sherbrooke ( Site 0202)
🇨🇦
Sherbrooke, Quebec, Canada
Daugavpils Regional Hospital ( Site 1502)
🇱🇻
Daugavpils, Latvia
Krasnoyarsk Regional Clinical Oncological Dispensary ( Site 1121)
🇷🇺
Krasnoyarsk, Krasnoyarskiy Kray, Russian Federation
First Moscow State Medical University n.a. I.M.Sechenov ( Site 1127)
🇷🇺
Moscow, Moskva, Russian Federation
City Clinical Oncology Center ( Site 1114)
🇷🇺
Saint Petersburg, Sankt-Peterburg, Russian Federation
Prof. Dr. Cemil Tascioglu Sehir Hastanesi ( Site 1216)
🇹🇷
Istanbul, Turkey
Dobrobut Medical Center ( Site 1320)
🇺🇦
Kyiv, Ukraine
UZ Gent ( Site 0101)
🇧🇪
Gent, Oost-Vlaanderen, Belgium
St. Marianna University School of Medicine Hospital ( Site 0657)
🇯🇵
Kawasaki, Kanagawa, Japan
P. Stradina Clinical University Hospital ( Site 1500)
🇱🇻
Riga, Latvia
Göztepe Prof. Dr. Süleyman Yalçın Şehir Hastanesi-oncology ( Site 1214)
🇹🇷
Istanbul, Turkey
Kartal Dr. Lutfi Kirdar Egitim ve Arast Hast ( Site 1211)
🇹🇷
Istanbul, Turkey
Ege Universitesi Tip Fakultesi Tulay Aktas Onkoloji Hastanesi ( Site 1204)
🇹🇷
Izmir, Turkey
University Medical Center New Orleans ( Site 1365)
🇺🇸
New Orleans, Louisiana, United States
Cancer & Hematology Centers of Western Michigan ( Site 1358)
🇺🇸
Grand Rapids, Michigan, United States
Hopital Cite de la Sante de Laval ( Site 0203)
🇨🇦
Laval, Quebec, Canada
Vilniaus Universiteto Ligonine Santaros Klinikos ( Site 1526)
🇱🇹
Vilnius, Lithuania
The Oncology Centre ( Site 0903)
🇿🇦
Durban, Limpopo, South Africa
Hospital General Universitario de Elche ( Site 1155)
🇪🇸
Elche, Alicante, Spain
Baskent University Adana Training Hospital ( Site 1205)
🇹🇷
Adana, Turkey
Hacettepe University Faculty of Medicine ( Site 1200)
🇹🇷
Ankara, Turkey
Medical Center Verum ( Site 1318)
🇺🇦
Kyiv, Kyivska Oblast, Ukraine
Shalimov s NI of Surgery and Transplantation ( Site 1321)
🇺🇦
Kyiv, Kyivska Oblast, Ukraine
Medical center of the Limited Liability Company Yulis ( Site 1314)
🇺🇦
Zaporizhzhia, Zaporizka Oblast, Ukraine
Cancercare Rondebosch Oncology ( Site 0904)
🇿🇦
Rondebosch, Western Cape, South Africa
Arkhangelsk Clinical Oncological Dispensary ( Site 1113)
🇷🇺
Arkhangelsk, Arkhangel Skaya Oblast, Russian Federation
MEDSI Clinical Hospital on Pyatnitsky Highway-Departmentof Antitumor Drug therapy ( Site 1129)
🇷🇺
Krasnogorsk, Moskovskaya Oblast, Russian Federation
Gazi Universitesi Tip Fakultesi ( Site 1215)
🇹🇷
Ankara, Turkey
Trakya Universitesi Tip Fakultesi ( Site 1210)
🇹🇷
Edirne, Turkey
GBUZ Republican Clinical Oncological Dispensary-Antitumor drug therapy department ( Site 1130)
🇷🇺
Ufa, Baskortostan, Respublika, Russian Federation
MROI n.a. P.A. Herzen - branch of FSBI NMICR of MoH of Russia ( Site 1128)
🇷🇺
Moscow, Moskva, Russian Federation
Istanbul Universitesi Cerrahpasa Tip Fakultesi ( Site 1202)
🇹🇷
Istanbul, Turkey
Medical Center Asklepion LLC ( Site 1309)
🇺🇦
Khodosivka, Kyivska Oblast, Ukraine
Communal non profit enterprise Regional Clinical Oncology Center ( Site 1304)
🇺🇦
Kharkiv, Kharkivska Oblast, Ukraine