MedPath

A Study Of Avelumab Alone Or In Combination With Pegylated Liposomal Doxorubicin Versus Pegylated Liposomal Doxorubicin Alone In Patients With Platinum Resistant/Refractory Ovarian Cancer (JAVELIN Ovarian 200)

Phase 3
Completed
Conditions
Ovarian Cancer
Interventions
Drug: PLD
Biological: avelumab
Registration Number
NCT02580058
Lead Sponsor
Pfizer
Brief Summary

A Phase 3 global study comparing avelumab alone to avelumab plus PLD and to PLD alone to demonstrate that avelumab given alone or in combination with PLD is superior to PLD alone in prolonging Overall Survival in patients with platinum resistant/platinum refractory ovarian cancer.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
566
Inclusion Criteria
  • Histologically confirmed epithelial ovarian, fallopian tube, or peritoneal cancer, including malignant mixed Müllerian tumors with high grade serous component.
  • Platinum resistant/refractory disease, defined as disease progression within 180 days following the last administered dose of platinum therapy (resistant), or lack of response or disease progression while receiving the most recent platinum based therapy (refractory), respectively.
  • Received up to 3 lines of systemic anticancer therapy for platinum sensitive disease, most recently platinum containing, and no prior systemic therapy for platinum resistant disease
  • Measurable disease by investigator assessment with at least 1 unidimensional measurable lesion by RECIST v.1.1 that has not previously been irradiated
  • Active autoimmune disease that might deteriorate when receiving an immunostimulatory agents. Patients with diabetes type I, vitiligo, psoriasis, hypo or hyperthyroid disease not requiring immunosuppressive treatment are eligible.

Mandatory tumor biopsy must be performed prior to enrollment for all patients (unless there is a documented clinical contraindication). In addition, availability of archived FFPE tumor tissue should be confirmed. If a patient underwent tumor tissue collection within 3 months prior to enrollment with no intervening treatment, and the sample is provided, then a new de novo tumor biopsy is not required.

Exclusion Criteria
  • Non epithelial tumor or ovarian tumors with low malignant potential (ie, borderline tumors).
  • Prior therapy with an anti PD 1, anti PD L1, anti PD L2, anti CD137, or anti cytotoxic T lymphocyte associated antigen 4 (CTLA 4) antibody (including ipilimumab, tremelimumab or any other antibody or drug specifically targeting T cell co stimulation or immune checkpoint pathways).
  • Known symptomatic brain metastases requiring steroids. Patients with previously diagnosed brain metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to study entry, have discontinued corticosteroid treatment for these metastases for at least 4 weeks prior to study entry and are neurologically stable.
  • Diagnosis of any other malignancy within 5 years prior to registration, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the breast or of the cervix.
  • Severe gastrointestinal conditions such as clinical or radiological evidence of bowel obstruction within 4 weeks prior to study entry, uncontrolled diarrhea in the last 4 weeks prior to enrollment, or history of inflammatory bowel disease.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PLDPLDArm C: PLD alone
avelumabavelumabArm A: avelumab alone
avelumab plus pegylated liposomal doxorubicin (PLD)avelumabArm B: avelumab plus PLD
avelumab plus pegylated liposomal doxorubicin (PLD)PLDArm B: avelumab plus PLD
Primary Outcome Measures
NameTimeMethod
Progression Free Survival (PFS) Based on Blinded Independent Central Review (BICR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1From randomization to date of first documentation of PD or death due to any cause whichever was first (up to 30 months); based on cutoff date: 19 September 2018.

PFS is defined as the time from date of randomization to the date of the first documentation of progression of disease (PD) or death due to any cause, whichever occurs first. PFS time was summarized by treatment arm using the Kaplan-Meier method. PFS based on BICR assessment was evaluated for this endpoint.

Overall Survival (OS)From randomization until the date of first documented progression or date of deaths from any cause, whichever came first, assessed up to 30 months (based on cutoff date: 19 September 2018).

OS is defined as the time from the date of randomization to the date of death due to any cause. OS time was summarized by treatment arm using the Kaplan-Meier method.

Secondary Outcome Measures
NameTimeMethod
Objective Response Rate (ORR) Based on BICR AssessmentTumor assessments as assessed by BICR were conducted at every 8 weeks from screening until documented disease progression (approximately up to 30 months); based on cutoff date: 19 September 2018.

Percentage of participants achieved objective response (OR) based on BICR assessment is presented for this endpoint. OR is defined as a complete response (CR, disappearance of all target lesions) or partial response (PR, \>=30% decrease under the baseline of the sum of diameters of all target measurable lesions) according to the RECIST (version 1.1) recorded from randomization until disease progression or death due to any cause. Both CR and PR must be confirmed by repeat assessments performed no less than 4 weeks after the criteria for response are first met and before the first documentation of disease progression. Only tumor assessments performed on or before the start date of any further anti-cancer therapies are considered in the assessment of best overall response.

PFS Based on Investigator Assessment According to RECIST Version 1.1From randomization to date of first documentation of PD or death due to any cause whichever was first (up to 30 months); based on cutoff date: 19 September 2018.

PFS is defined as the time from date of randomization to the date of the first documentation of PD or death due to any cause, whichever occurs first. PFS time was summarized by treatment arm using the Kaplan-Meier method.

ORR Based on Investigator AssessmentTumor assessments as assessed by investigator were conducted at every 8 weeks from screening until documented disease progression, up to 30 months; based on cutoff date: 19 September 2018.

Percentage of participants achieved OR based on investigator assessment is presented for this endpoint. OR is defined as a CR (disappearance of all target lesions) or PR (\>=30% decrease under the baseline of the sum of diameters of all target measurable lesions) according to the RECIST (version 1.1) recorded from randomization until disease progression or death due to any cause. The ORR on each randomized treatment arm were estimated by dividing the number of participants with OR (CR or PR) by number of participants randomized to the respective treatment arm.

Disease Control (DC) Rate Based on BICR AssessmentTumor assessments as assessed by investigator were conducted at every 8 weeks from screening until documented disease progression, up to 30 months; based on cutoff date: 19 September 2018.

Percentage of participants achieving DC based on BICR assessment is presented in this endpoint. DC is a best overall response of CR (disappearance of all target lesions), PR (\>=30% decrease under the baseline of the sum of diameters of all target measurable lesions), non-complete response/non-progressive disease or stable disease (SD) according to the RECIST version 1.1.

DC Rate Based on Investigator AssessmentTumor assessments as assessed by investigator were conducted at every 8 weeks from screening until documented disease progression, up to 30 months; based on cutoff date: 19 September 2018.

Percentage of participants achieving DC based on investigator assessment is presented in this endpoint. DC is a best overall response of CR (disappearance of all target lesions), PR (\>=30% decrease under the baseline of the sum of diameters of all target measurable lesions), non-complete response/non-progressive disease or SD according to the RECIST version 1.1.

Time to Deterioration in Abdominal/GI Symptom Subscale of EORTC QLQ-OV28From Day 1 of Cycle 1 to prior to end of treatment/withdrawal visit, based on cutoff date: 19 September 2018.

The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Ovarian Cancer 28 (EORTC QLQ-OV28) is a 28 item instrument with 7 functional domain subscales. Time to deterioration was defined as the time from randomization to the first time the participant's score showed a 15-point or higher increase in the score of the abdominal/GI symptom subscale of the EORTC QLQ-OV28.

Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)From the time of the first dose of study treatment through a minimum of 30 days + last dose of study treatment, start day of new anti-cancer therapy -1 day (up to 70 months); based on cutoff date: 13 July 2022.

An adverse event (AE) is any untoward medical occurrence in a clinical investigation patient administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening; initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; progression of the malignancy under study. Treatment emergent AEs are those events with onset dates occurring during the on-treatment period for the first time, or if the worsening of an event is during the on-treatment period.

Number of Participants With Laboratory AbnormalitiesFrom screening to the end of treatment/withdrawal visit, up to 2.7 years, based on cutoff date: 19 September 2018.

The number of participants with following laboratory abnormalities meeting any of the Grades 1 to 4 classified according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) toxicity grading version 4.03 were summarized: hematology (anemia, lymphocyte count decreased, neutrophil count decreased; and platelet count decreased) and chemistry laboratory tests (creatinine increased; serum amylase increased and lipase increased).

Number of Participants With Electrocardiogram (ECG) AbnormalitiesFrom screening to the end of treatment/withdrawal visit, up to 2.7 years, based on cutoff date: 19 September 2018.

Categorical summarization ECG criteria were as follows: 1) QT interval, QTcB, QTcF and QTcP: increase from baseline \>30 ms or 60 ms; absolute value \> 450 ms, \>480 ms and \> 500 ms; 2) heart rate (HR): change from baseline \>=20 bpm and absolute value \<=50 bpm or \>=120 bpm; 3) PR interval: absolute value \>=220 ms and increase from baseline \>=20 ms; 4) QRS: \>= 120 ms.

Serum Trough Concentration (Ctrough) For Avelumab Following Cycle 2 Day 1 Pegylated Liposomal Doxorubicin (PLD) DoseAt predose (0 H) on Cycle 2 Day 1

Ctrough was defined as predose concentration during multiple dosing, and can be observed directly from data.

Area Under The Concentration Time Profile From Time Zero to 24 Hours (AUC24) For Doxorubicin Following Cycle 2 Day 1 PLD DoseFrom 0 through 24 hours postdose

AUC24 was defined as area under the concentration time profile from time zero to 24 hours.

Area Under The Concentration Time Profile From Time Zero to 336 Hours (AUC336) For Doxorubicin Following Cycle 2 Day 1 PLD DoseFrom predose (0 H) of Cycle 2 Day 1 through 336 hours postdose

AUC336 was defined as area under the concentration time profile from time zero to 336 hours.

Area Under The Concentration Time Profile From Time Zero to The Last Quantifiable Concentration (AUClast) For Doxorubicin Following Cycle 2 Day 1 PLD DoseFrom predose (0 H) of Cycle 2 Day 1 through 336 hours postdose

AUClast was defined as area under the concentration time profile from time zero to the time of the last quantifiable concentration (Clast).

Number of Participants With Treatment-Induced Neutralizing Antibody (nAb)At predose (0 H) of select cycles starting from Cycle 1 through Cycle 24, at end of treatment and 30 days after the last dose of avelumab

Treatment-induced nAb was defined as participant who was not nAb positive at baseline and had at least one positive post-baseline nAb result; or if participant did not have a baseline sample, the participant had at least one positive past-baseline ADA result.

Duration of Response (DR) Based on BICR AssessmentTumor assessments as assessed by investigator were conducted at every 8 weeks from screening until documented disease progression, up to 30 months; based on cutoff date: 19 September 2018.

DR is defined, for participants with an OR per RECIST version 1.1, as the time from the first documentation of objective tumor response (CR \[disappearance of all target lesions\] or PR \[\>=30% decrease under the baseline of the sum of diameters of all target measurable lesions\]) to the first documentation of objective tumor progression or death due to any cause, whichever occurs first.

Number of Participants With % Left Ventricular Ejection Fraction (LVEF) Decrease From BaselineScreening, Cycle 3 Day 1 (repeated every 2 cycles) to the end of treatment/withdrawal visit, based on cutoff date: 19 September 2018.

LVEF decrease was summarized by multiple-gated acquisition (MUGA)/ echocardiogram (ECHO) parameter. Participants with a LVEF% \>=10 points and \>= 15 points decrease from baseline during the on-treatment period were summarized.

Number of Participants With PD-L1 Expression for PFS (Based on BICR Assessment) and for OSBiomarkers are measured only at screening.

PD-L1 expression was assessed by immunohistochemistry. Participants were considered positive for PD-L1 if their baseline tissue sample demonstrated PD-L1 expression on \>=1% of tumor cells or \>=5% of immune cells.

Number of Participants With CD8 Expression for PFS (Based on BICR Assessment) and for OSBiomarkers are measured only at screening.

Tumor infiltrating CD8 positive (CD8+) T lymphocytes was assessed by immunohistochemistry. Participants were considered positive for CD8 T cells if their baseline tissue sample demonstrated presence of \>=1% CD8+ cells across the area of the tumor.

Change From Baseline in EQ-VAS Score at End of TreatmentBaseline and end of treatment/withdrawal visit

The EuroQol- 5 Dimensions- 5 Levels (EQ-5D-5L) questionnaire consists of the EQ-5D-5L descriptive system and a visual analogue scale (the EuroQol-visual analogue scale \[EQ-VAS\]). The respondent's self-rated health is assessed on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state) by the EQ-VAS.

DR Based on Investigator AssessmentTumor assessments as assessed by investigator were conducted at every 8 weeks from screening until documented disease progression, up to 30 months; based on cutoff date: 19 September 2018.

DR is defined, for participants with an OR per RECIST version 1.1, as the time from the first documentation of objective tumor response (CR \[disappearance of all target lesions\] or PR \[\>=30% decrease under the baseline of the sum of diameters of all target measurable lesions\]) to the first documentation of objective tumor progression or death due to any cause, whichever occurs first.

Change From Baseline in Vital Signs - Blood PressureFrom screening to the end of treatment/withdrawal visit, up to 2.7 years, based on cutoff date: 19 September 2018.

Vital signs included blood pressure and pulse rate. Changes from baseline in sitting diastolic blood pressure (DBP) and systolic blood pressure (SBP) were summarized.

Change From Baseline in Vital Signs - Pulse RateFrom screening to the end of treatment/withdrawal visit, up to 2.7 years, based on cutoff date: 19 September 2018.

Vital signs included blood pressure and pulse rate. Changes from baseline in sitting pulse rate were summarized.

Number of Participants With Improved, Stable and Deterioration Based on 10-Point Change for EORTC QLQ-C30 Global QoLDay 1 of Cycle 1, Day 1 of each subsequent cycle, end of treatment/withdrawal visit and the 30, 60 and 90 days safety follow up visits, based on cutoff date: 19 September 2018.

The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC QLQ-C30) is a 30 question survey and includes 5 functional domain subscales, global health status/quality of life, disease/treatment related symptoms, and the perceived financial impact of disease. Higher scores are reflective of a greater presence of symptoms.

Serum Maximum Concentration (Cmax) For Avelumab Following Cycle 2 Day 1 PLD DoseAt postdose (end of infusion, 1H) on Cycle 2 Day 1

Cmax was defined as maximum observed serum concentration, and can be observed directly from data.

Cmax For Doxorubicin Following Cycle 2 Day 1 PLD DoseFrom predose (0 H) of Cycle 2 Day 1 through 336 hours postdose

Cmax was defined as maximum observed serum concentration, and can be observed directly from data.

Number of Participants With Treatment-Boosted Anti-Drug Antibody (ADA)At predose (0 H) of select cycles starting from Cycle 1 through Cycle 24, at end of treatment and 30 days after the last dose of avelumab

Treatment-boosted ADA was defined as a positive ADA result at baseline and the titer ≥ 8×baseline titer at least once after treatment with avelumab.

Number of Participants With Treatment-Induced ADAAt predose (0 H) of select cycles starting from Cycle 1 through Cycle 24, at end of treatment and 30 days after the last dose of avelumab

Treatment-induced ADA was defined as participant who was ADA-negative at baseline and has at least one positive post-baseline ADA result; or if participant did not have a baseline sample, the participant had at least one positive past-baseline ADA result.

Trial Locations

Locations (256)

Maryland Oncology Hematology, P.A.

🇺🇸

Columbia, Maryland, United States

Texas Oncology - The Woodlands, Gynecologic Oncology

🇺🇸

The Woodlands, Texas, United States

General Hospital of Athens Alexandra

🇬🇷

Athens, Greece

Chang Gung Memorial Hospital - Linkou Branch

🇨🇳

Taoyuan City, Taiwan

National Cancer Centre Singapore

🇸🇬

Singapore, Singapore

Universitatsspital Zurich, Universitares Herzzentrum Zurich

🇨🇭

Zurich, Switzerland

Carilion Clinic

🇺🇸

Roanoke, Virginia, United States

Arizona Oncology Associates, PC-HAL

🇺🇸

Tempe, Arizona, United States

University of California, Irvine/UC Irvine Health

🇺🇸

Orange, California, United States

Arizona Oncology Associates, PC - HAL

🇺🇸

Scottsdale, Arizona, United States

Hope Women's Cancer Centers

🇺🇸

Asheville, North Carolina, United States

University of New Mexico Comprehensive Cancer Center

🇺🇸

Albuquerque, New Mexico, United States

Rocky Mountain Cancer Centers

🇺🇸

Lakewood, Colorado, United States

The University of Kansas Clinical Research Center

🇺🇸

Fairway, Kansas, United States

Center of Hope at Renown Regional Medical Center

🇺🇸

Reno, Nevada, United States

CHU de Liege - Sart Tilman

🇧🇪

Liege, Belgium

Cross Cancer Institute

🇨🇦

Edmonton, Alberta, Canada

Icon Cancer Foundation

🇦🇺

South Brisbane, Queensland, Australia

Mater Cancer Care Centre

🇦🇺

South Brisbane, Queensland, Australia

The Royal Women's Hospital

🇦🇺

Parkville, Victoria, Australia

British Columbia Cancer Agency-Vancouver Centre

🇨🇦

Vancouver, British Columbia, Canada

Medizinische Universitat Graz, LKH-Univ. Klinikum Graz

🇦🇹

Graz, Austria

Icon Cancer Care Wesley

🇦🇺

Auchenflower, Queensland, Australia

Institut Jules Bordet

🇧🇪

Brussels, Belgium

AZ Groeninge Hospital

🇧🇪

Kortrijk, Belgium

Clinique et Maternite Sainte Elisabeth

🇧🇪

Namur, Belgium

Mater Pharmacy Services

🇦🇺

Brisbane, Queensland, Australia

Health Sciences Centre

🇨🇦

Winnipeg, Manitoba, Canada

Icon Cancer Care Chermside

🇦🇺

Chermside, Queensland, Australia

Cabrini Health Limited

🇦🇺

Malvern, Victoria, Australia

Peter MacCallum Cancer Centre

🇦🇺

Melbourne, Victoria, Australia

Sunnybrook Research Institute

🇨🇦

Toronto, Ontario, Canada

Humanitas Cliniche Gavazzeni

🇮🇹

Bergamo, Italy

State Budgetary Healthcare Institution "Clinical oncology dispensary #1"

🇷🇺

Krasnodar, Russian Federation

Humanitas, Unita Operativa di Cardiologia 2

🇮🇹

Bergamo, Italy

Institut Catala d'Oncologia - Hospital Duran y Reynalds

🇪🇸

L'Hospitalet de Llobregat, Barcelona, Spain

C D C, Sede di Torino Centro

🇮🇹

Torino, Italy

Ambulatorio dott. Francesco Cavanna, Medico Chirurgo

🇮🇹

Piacenza, Italy

Clinical Trial Pharmacy, National Cheng Kung University Hospital

🇨🇳

Tainan city, Taiwan

Northampton General Hospital NHS Trust

🇬🇧

Northampton, Northamptonshire, United Kingdom

East and North Hertfordshire NHS Trust

🇬🇧

Northwood, Middlesex, United Kingdom

State Regional Budgetary Healthcare Institution "Regional clinical oncology dispensary"

🇷🇺

Velikiy Novgorod, Russian Federation

Clinical Trial Pharmacy, Keimyung University Dongsan Medical Center

🇰🇷

Daegu, Korea, Republic of

State Budgetary Healthcare Institution "Orenburg Regional Clinical Oncological Dispensary"

🇷🇺

Orenburg, Russian Federation

State Budget Institution of Healthcare Saint Petersburg Clinical Scientific - Practice Center

🇷🇺

Saint Petersburg, Russian Federation

Hospital MD Anderson

🇪🇸

Madrid, Spain

Hospital Universitario Virgen de Valme

🇪🇸

Sevilla, Spain

SPZOZ Wojewodzki Szpital Specjalistyczny nr 3 w Rybniku, Apteka Szpitalna

🇵🇱

Rybnik, Poland

The Clatterbridge Cancer Centre

🇬🇧

Bebington, Wirral, Merseyside, United Kingdom

lnstitut Catala d Oncologia de Girona. Hospital Universitario Dr. Josep Trueta

🇪🇸

Girona, Spain

National University Hospital

🇸🇬

Singapore, Singapore

National Cancer Centre Singapore Pharmacy

🇸🇬

Singapore, Singapore

Chemotherapy Pharmacy, Chang Gung Memorial Hospital - Linkou Branch

🇨🇳

Taoyuan City, Taiwan

National Taiwan University Hospital

🇨🇳

Taipei, Taiwan

Imperial College Healthcare NHS Trust

🇬🇧

London, United Kingdom

Szpital Kliniczny Przemienienia Panskiego Uniwersytetu Medycznego

🇵🇱

Poznan, Poland

Raffles Hospital

🇸🇬

Singapore, Singapore

Nottingham University Hospital NHS Trust

🇬🇧

Nottingham, United Kingdom

Hospital Universitario La Paz

🇪🇸

Madrid, Spain

Guy's & St. Thomas' NHS Foundation Trust

🇬🇧

London, United Kingdom

Mackay Memorial Hospital

🇨🇳

Taipei City, Taiwan

Universitatsspital Zurich, Institut fur diagnostische und interventionelle Radiologie

🇨🇭

Zurich, Switzerland

Centro Integral Oncologico Clara Campal

🇪🇸

Madrid, Spain

Hospital Universitario Reina Sofia

🇪🇸

Cordoba, Spain

The Royal Marsden NHS Foundation Trust

🇬🇧

London, United Kingdom

Universitatsspital Basel

🇨🇭

Basel, Basel-stadt, Switzerland

National Cheng Kung University Hospital

🇨🇳

Tainan City, Taiwan

Clinical Trial Pharmacy, Mackay Memorial Hospital

🇨🇳

Taipei City, Taiwan

Nottingham University Hospitals NHS Trust

🇬🇧

Nottingham, United Kingdom

NHS Greater Glasgow and Clyde

🇬🇧

Glasgow, United Kingdom

Universitatsspital Basel, Frauenklinik

🇨🇭

Basel, Basel-stadt, Switzerland

Shaare Zedek Medical Center

🇮🇱

Jerusalem, Israel

Atlanta Gynecologic Oncology

🇺🇸

Atlanta, Georgia, United States

Northside Hospital - Pharmacy

🇺🇸

Atlanta, Georgia, United States

Cleveland Clinic Taussig Cancer Center

🇺🇸

Cleveland, Ohio, United States

Utah Cancer Specialists

🇺🇸

Salt Lake City, Utah, United States

University Gynecologic Oncology

🇺🇸

Atlanta, Georgia, United States

Massachusetts General Hospital

🇺🇸

Boston, Massachusetts, United States

Brigham Women's Hospital

🇺🇸

Boston, Massachusetts, United States

Dana Farber Cancer Institute

🇺🇸

Boston, Massachusetts, United States

Fairview Hospital Moll Pavilion Cancer Center

🇺🇸

Cleveland, Ohio, United States

Cleveland Clinic

🇺🇸

Cleveland, Ohio, United States

Texas Oncology - San Antonio Medical Center

🇺🇸

San Antonio, Texas, United States

The Sarah Cannon Research Institute

🇺🇸

Nashville, Tennessee, United States

Azienda USL 4 Toscana Centro

🇮🇹

Prato, Italy

Centre Antoine Lacassagne

🇫🇷

Nice cedex 2, France

Hôpital Européen Georges Pompidou

🇫🇷

Paris, France

Institut de Cancérologie de Lorraine

🇫🇷

Vandoeuvre-lès-Nancy, France

Oxford University Hospitals NHS Foundation Trust

🇬🇧

Headington, Oxford, United Kingdom

Nippon Medical School Musashikosugi Hospital

🇯🇵

Kawasaki, Kanagawa, Japan

National Defense Medical College Hospital

🇯🇵

Tokorozawa, Saitama, Japan

Seirei Hamamatsu General Hospital

🇯🇵

Hamamatsu, Shizuoka, Japan

Metro North Hospital and Health Service

🇦🇺

Herston, Queensland, Australia

Arizona Oncology Associates, PC - HOPE

🇺🇸

Tucson, Arizona, United States

Highlands Oncology Group

🇺🇸

Rogers, Arkansas, United States

Sansum Clinic

🇺🇸

Solvang, California, United States

Florida Cancer Specialists

🇺🇸

West Palm Beach, Florida, United States

The University of Kansas Cancer Center and Medical Pavilion

🇺🇸

Westwood, Kansas, United States

Northwest Georgia Oncology Centers, P.C.

🇺🇸

Marietta, Georgia, United States

Maryland Oncology Hematology P.A.

🇺🇸

Silver Spring, Maryland, United States

Southwest GYN Oncology Associates, Inc.

🇺🇸

Albuquerque, New Mexico, United States

Mission Hospital, Inc.

🇺🇸

Asheville, North Carolina, United States

Hillcrest Hospital Hirsch Cancer Center Pharmacy

🇺🇸

Mayfield Heights, Ohio, United States

Hillcrest Hospital

🇺🇸

Mayfield Heights, Ohio, United States

Investigational Drug Services, University of Pennsylvania

🇺🇸

Philadelphia, Pennsylvania, United States

Willamette Valley Cancer Institute and Research Center

🇺🇸

Eugene, Oregon, United States

Fairview Hospital Moll Pavilion Pharmacy

🇺🇸

Cleveland, Ohio, United States

The University of Pennsylvania Health System

🇺🇸

Philadelphia, Pennsylvania, United States

Tennessee Oncology, PLLC

🇺🇸

Smyrna, Tennessee, United States

Texas Oncology-Austin Central

🇺🇸

Austin, Texas, United States

Texas Oncology-South Austin

🇺🇸

Austin, Texas, United States

Texas Oncology -Fort Worth Cancer Center

🇺🇸

Fort Worth, Texas, United States

Texas Oncology - Bedford

🇺🇸

Bedford, Texas, United States

US Oncology Investigational Products Center (IPC)

🇺🇸

Irving, Texas, United States

US Oncology Investigational Products Center

🇺🇸

Irving, Texas, United States

Carilion Clinic Gynecologic Oncology

🇺🇸

Roanoke, Virginia, United States

Medizinische Universitat Innsbruck

🇦🇹

Innsbruck, Austria

Rivercity Pharmacy

🇦🇺

Auchenflower, Queensland, Australia

Epic Pharmacy,Newcastle Private Hospital

🇦🇺

New Lambton Heights, New South Wales, Australia

Newcastle Private Hospital Pty Limited

🇦🇺

Newcastle, New South Wales, Australia

Clinical Research Unit

🇦🇺

Herston, Queensland, Australia

Oncology Pharmacy

🇦🇺

Herston, Queensland, Australia

Icon Cancer Care Southport

🇦🇺

Southport, Queensland, Australia

Icon Cancer Care

🇦🇺

South Brisbane, Queensland, Australia

Royal Melbourne Hospital

🇦🇺

Parkville, Victoria, Australia

St. Boniface General Hospital

🇨🇦

Winnipeg, Manitoba, Canada

Tom Baker Cancer Centre

🇨🇦

Calgary, Alberta, Canada

CancerCare Manitoba

🇨🇦

Winnipeg, Manitoba, Canada

The Ottawa Hospital

🇨🇦

Ottawa, Ontario, Canada

Princess Margaret Cancer Centre

🇨🇦

Toronto, Ontario, Canada

Nova Scotia Health Authority, QEII Health Sciences Centre, Nova Scotia Cancer Centre

🇨🇦

Halifax, Nova Scotia, Canada

Nova Scotia Health Authority, QEII Health Sciences Centre

🇨🇦

Halifax, Nova Scotia, Canada

McGill University Health Centre - Glen Site

🇨🇦

Montreal, Quebec, Canada

Oncology Pharmacy McGill University Health Centre

🇨🇦

Montreal, Quebec, Canada

Jewish General Hospital

🇨🇦

Montreal, Quebec, Canada

Vseobecna fakultni nemocnice v Praze, Fakultni poliklinika

🇨🇿

Praha 2, Czech Republic, Czechia

Fakultni nemocnice Olomouc

🇨🇿

Olomouc, Czechia

Fakultni nemocnice Ostrava

🇨🇿

Ostrava-Poruba, Czechia

Vseobecna fakultni nemocnice v Praze, Nemocnicni lekarna,

🇨🇿

Praha 2, Czechia

Fakultni nemocnice v Motole

🇨🇿

Praha 5, Czechia

Vseobecna fakultni nemocnice v Praze, Neurologicka klinika

🇨🇿

Praha 2, Czechia

Krajska zdravotni a.s., Masarykova nemocnice v Usti nad Labem, o.z

🇨🇿

Usti nad Labem, Czechia

Vseobecna fakultni nemocnice v Praze

🇨🇿

Praha 2, Czechia

Aalborg University Hospital

🇩🇰

Aalborg, Denmark

Rigshospitalet

🇩🇰

Copenhagen, Denmark

Centre Leon Berard

🇫🇷

Lyon cedex 08, France

Centre Francois Baclesse

🇫🇷

Caen Cedex 5, France

Service de Radiologie

🇫🇷

LYON cedex 8, France

Centre Hospitalier Lyon Sud

🇫🇷

Pierre Benite cedex, France

Gustave Roussy Cancer Campus

🇫🇷

Villejuif cedex, France

General Oncology Hospital of Kifissia "Agioi Anargiroi", 2nd Department of Medical Oncology

🇬🇷

Athens/New Kifissia, Greece

Mater Private Hospital

🇮🇪

Dublin, Ireland

Princess Margaret Hospital

🇭🇰

Hong Kong, Hong Kong

Orszagos Onkologiai Intezet, Nogyogyaszati Osztaly

🇭🇺

Budapest, Hungary

Orszagos Onkologiai Intezet, Gyogyszertar

🇭🇺

Budapest, Hungary

Debreceni Egyetem Klinikai Gyogyszertar

🇭🇺

Debrecen, Hungary

Mater Misericordiae University Hospital

🇮🇪

Dublin 7, Dublin, Ireland

Debreceni Egyetem Klinikai Kozpont

🇭🇺

Debrecen, Hungary

Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz-Rendelointezet, Onkologiai Kozpont

🇭🇺

Szolnok, Hungary

St Vincent's University Hospital

🇮🇪

Dublin 4, Ireland

St James's Hospital

🇮🇪

Dublin, Ireland

Mater Misericoridae University Hospital

🇮🇪

Dublin, Ireland

Poliambulatorio Specialistico Villa Salute

🇮🇹

Manerbio, Brescia, Italy

Congregazione delle Suore Infermiere dell'Addolorata

🇮🇹

Como, Italy

ASST Fatebenefratelli Sacco

🇮🇹

Miano, Milano, Italy

Servizio Sanitario Regionale Emilia-Romagna

🇮🇹

Rimini, Italy

Fondazione del Piemonte per l'Oncologia

🇮🇹

Candiolo, Torino, Italy

Habilita, San Marco Bergamo

🇮🇹

Bergamo, Italy

Fondazione Poliambulanza Istituto Ospedelario

🇮🇹

Brescia, Italy

Fondazione Teresa Camplani

🇮🇹

Cremona, Italy

Regione Lombardia, A O Istituti Ospitalieri di Cremona

🇮🇹

Cremona, Italy

Istituto Europeo di Oncologia

🇮🇹

Milano, Italy

Regione Lombardia, ASST Cremona

🇮🇹

Cremona, Italy

Azienda Unita Sanitaria Locale di Piacenza

🇮🇹

Piacenza, Italy

Azienda USL 4 Prato

🇮🇹

Prato, Italy

Ehime University Hospital

🇯🇵

Toon, Ehime, Japan

Shikoku Cancer Center

🇯🇵

Matsuyama, Ehime, Japan

Hokkaido University Hospital

🇯🇵

Sapporo, Hokkaido, Japan

Hyogo Cancer Center

🇯🇵

Akashi, Hyogo, Japan

University of Tsukuba Hospital

🇯🇵

Tsukuba, Ibaraki, Japan

Saitama Cancer Center

🇯🇵

Kita-adachi-gun, Saitama, Japan

Tokai University Hospital

🇯🇵

Isehara, Kanagawa, Japan

Tohoku University Hospital

🇯🇵

Sendai, Miyagi, Japan

Saitama Medical University International Medical Center

🇯🇵

Hidaka, Saitama, Japan

Yokohama City University Hospital

🇯🇵

Yokohama, Kanagawa, Japan

The University of Tokyo Hospital

🇯🇵

Bunkyo-ku, Tokyo, Japan

Jichi Medical University Hospital

🇯🇵

Shimotsuke, Tochigi, Japan

National Cancer Center Hospital

🇯🇵

Chuo-ku, Tokyo, Japan

Kagoshima University Hospital

🇯🇵

Kagoshima, Japan

Kagoshima City Hospital

🇯🇵

Kagoshima, Japan

Niigata Cancer Center Hospital

🇯🇵

Niigata, Japan

Keimyung University Dongsan Medical Center

🇰🇷

Daegu, Korea, Republic of

National Cancer Center

🇰🇷

Goyangsi, Gyeonggi-do, Korea, Republic of

Seoul National University Hospital

🇰🇷

Seoul, Korea, Republic of

Asan Medical Center

🇰🇷

Seoul, Korea, Republic of

Korea University Anam Hospital

🇰🇷

Seoul, Korea, Republic of

Severance Hospital, Yonsei University Health System, Clinical Trial Pharmacy

🇰🇷

Seoul, Korea, Republic of

Samsung Medical Center Clinical Trial Pharmacy

🇰🇷

Seoul, Korea, Republic of

Severance Hospital, Yonsei University Health System

🇰🇷

Seoul, Korea, Republic of

Department of Pharamacy, The Catholic University of Korea, Seoul St. Mary's Hospital

🇰🇷

Seoul, Korea, Republic of

The Catholic University of Korea

🇰🇷

Seoul, Korea, Republic of

The Catholic University of Korea, Seoul St. Mary's Hospital

🇰🇷

Seoul, Korea, Republic of

Universitair Medisch Centrum Groningen

🇳🇱

Groningen, Netherlands

LUMC

🇳🇱

Leiden, Netherlands

Department of Obstetrics and Gynecology, Haukeland University Hospital

🇳🇴

Bergen, Norway

Maastricht Universitair Medisch Centrum

🇳🇱

Maastricht, Netherlands

Oslo Universitetssykehus

🇳🇴

Oslo, Norway

Sykehusapoteket Oslo

🇳🇴

Oslo, Norway

Sykehusapoteket i Bergen

🇳🇴

Bergen, Norway

Centrum Onkologii, Instytut im. M. Sklodowskiej-Curie, Oddzial w Krakowie, Apteka Szpitalna

🇵🇱

Krakow, Poland

Wojewodzki Szpital Specjalistyczny w Olsztynie, Apteka Szpitalna

🇵🇱

Olsztyn, Poland

Wojewodzki Szpital Specjalistyczny w Olsztynie

🇵🇱

Olsztyn, Poland

SPZOZ Wojewodzki Szpital Specjalistyczny nr 3 w Rybniku

🇵🇱

Rybnik, Poland

State Budgetary Healthcare Institution "Oncology Center #2" of the Ministry of Healthcare

🇷🇺

Sochi, Krasnodar Region, Russian Federation

Szpital Kliniczny Przemienienia Panskiego Uniwersytetu Medycznego im. Karola Marcinkowskiego w

🇵🇱

Poznan, Poland

State Budgetary Healthcare Institution Pyatigorsk Oncology Dispensary

🇷🇺

Pyatigorsk, Stavropol Region, Russian Federation

Evimed Llc

🇷🇺

Chelyabinsk, Russian Federation

State Budgetary Healthcare Institution

🇷🇺

Chelyabinsk, Russian Federation

Federal State Budgetary Institution "Russian Cancer Research Center n.a. N.N. Blokhin"

🇷🇺

Moscow, Russian Federation

State Budgetary Healthcare Institution of Nizhegorogsky region

🇷🇺

Nizhniy Novgorod, Russian Federation

Universitaetsspital Zurich, Klinik fuer Gynakologie

🇨🇭

Zurich, Switzerland

Oncology Institute of Southern Switzerland (IOSI)

🇨🇭

Bellinzona, Ticino, Switzerland

Universitatsspital Zurich, Clinical Trials Center

🇨🇭

Zurich, Switzerland

Clinical Trial Pharmacy, Koo Foundation Sun Yat-Sen Cancer Center

🇨🇳

Taipei City, Taiwan

Ross Hall Hospital

🇬🇧

Glasgow, CITY OF Glasgow, United Kingdom

Clinical Trial Pharmacy, Taipei Veterans General Hospital

🇨🇳

Taipei, Taiwan

Taipei Veterans General Hospital

🇨🇳

Taipei, Taiwan

The Clatterbridge Cancer Centre NHS Foundation Trust

🇬🇧

Bebington, Wirral, Merseyside, United Kingdom

Spire Healthcare Limited (St. Anthony's Hospital)

🇬🇧

Sutton, Surrey, United Kingdom

Guy's & St Thomas' NHS Foundation Trust

🇬🇧

London, United Kingdom

University College London Hospital NHS Foundation Trust

🇬🇧

London, United Kingdom

The Christie Hospital NHS Foundation Trust

🇬🇧

Manchester, United Kingdom

Samsung Medical Center

🇰🇷

Seoul, Korea, Republic of

Pharmacy Department

🇮🇪

Dublin 4, Ireland

University Hospital Waterford

🇮🇪

Waterford, Ireland

Cambridge University Hospitals NHS Foundation Trust

🇬🇧

Cambridge, Cambridgeshire, United Kingdom

Centrum Onkologii, Instytut im. M. Sklodowskiej-Curie, Oddzial w Krakowie

🇵🇱

Krakow, Poland

Koo Foundation Sun Yat-Sen Cancer Center

🇨🇳

Taipei City, Taiwan

University Hospital Gent

🇧🇪

Gent, EAST Flanders, Belgium

Luzerner Kantonsspital, Medizinische Onkologie, Studienzentrale Onkologie

🇨🇭

Luzern 16, Luzern, Switzerland

Kantonsapotheke Zurich

🇨🇭

Zurich, Switzerland

Fox Chase Cancer Center

🇺🇸

Philadelphia, Pennsylvania, United States

Norton Cancer Institute, Norton Healthcare Pavilion

🇺🇸

Louisville, Kentucky, United States

Norton Healthcare Pharmacy, Attn: Marlon Baranda, Pharm D

🇺🇸

Louisville, Kentucky, United States

Norton Hospital

🇺🇸

Louisville, Kentucky, United States

Norton Cancer Institute, St. Matthews Campus

🇺🇸

Louisville, Kentucky, United States

Norton Women's and Children's Hospital

🇺🇸

Louisville, Kentucky, United States

Norton Brownsboro Hospital

🇺🇸

Louisville, Kentucky, United States

Norton Cancer Institute, Brownsboro Hospital Campus

🇺🇸

Louisville, Kentucky, United States

The University of Kansas Cancer Center, CCP - North

🇺🇸

Kansas City, Missouri, United States

Novant Health Oncology Specialists

🇺🇸

Winston-Salem, North Carolina, United States

Froedtert and The Medical College of Wisconsin

🇺🇸

Milwaukee, Wisconsin, United States

Froedtert Hospital

🇺🇸

Milwaukee, Wisconsin, United States

Universitaire Ziekenhuizen Leuven

🇧🇪

Leuven, Belgium

British Columbia Cancer Agency - Sindi Ahluwalia Hawkins Centre for the Southern Interior

🇨🇦

Kelowna, British Columbia, Canada

University of Hong Kong

🇭🇰

Hong Kong, Hong Kong

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