Temsirolimus, Carboplatin, and Paclitaxel as First-Line Therapy in Treating Patients With Newly Diagnosed Stage III-IV Clear Cell Ovarian Cancer
- Conditions
- Ovarian Clear Cell CystadenocarcinomaStage III Ovarian CancerStage IV Ovarian Cancer
- Interventions
- Drug: CarboplatinDrug: DocetaxelOther: Laboratory Biomarker AnalysisDrug: PaclitaxelDrug: Temsirolimus
- Registration Number
- NCT01196429
- Lead Sponsor
- National Cancer Institute (NCI)
- Brief Summary
This phase II trial studies how well temsirolimus, carboplatin, and paclitaxel as first-line therapy works in treating patients with newly diagnosed stage III-IV clear cell ovarian cancer. Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving temsirolimus with combination chemotherapy may be an effective treatment for ovarian cancer.
- Detailed Description
PRIMARY OBJECTIVES:
I. To assess the activity of the study regimen as measured by the proportion of patients who are alive and progression-free for at least 12 months after study entry in patients with newly diagnosed stage III or IV clear cell ovarian cancer in the following populations: patients in the United States (U.S.) and worldwide (outside of Japan) and patients in Japan.
II. To compare progression-free survival in newly diagnosed stage III or IV clear cell ovarian cancer patients in patients in the U.S. and worldwide (outside of Japan) versus patients in Japan.
SECONDARY OBJECTIVES:
I. To characterize the duration of overall survival and progression-free survival in each population.
II. To examine the frequency and severity of adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4 in each population.
III. To estimate the rate of objective tumor response in patients with measurable disease.
TERTIARY OBJECTIVES:
I. To explore whether immunohistochemical (IHC) expression of components of the mammalian target of rapamycin (mTOR) signaling pathway (phosphatase and tensin homolog \[PTEN\], total and phosphorylated protein kinase B \[Akt\], as well as, ATP-binding cassette, sub-family C \[CFTR/MRP\], member 3 \[ABCC3\] \[MRP3\], ATPase, H+ transporting, lysosomal accessory protein 1 \[AB CF2\], cyclin E, and vascular endothelial growth factor \[VEGF\]) are associated with outcome, nationality or clinical characteristics.
II. To explore whether there is any differences in differential gene expression profiles between U.S. and worldwide (outside of Japan) versus Japanese patients.
OUTLINE:
Patients receive paclitaxel\* intravenously (IV) over 3 hours and carboplatin IV over 30 minutes on day 1 and temsirolimus IV on days 1 and 8. Treatment repeats every 3 weeks for 6 courses. Patients then receive consolidation therapy comprising temsirolimus IV on days 1, 8, and 15. Treatment repeats every 3 weeks for 11 courses in the absence of disease progression or unacceptable toxicity.
NOTE: \* For circumstances in which docetaxel should be substituted for paclitaxel, docetaxel is given IV over 1 hour.
After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 90
- Patients must have stage III or IV clear cell ovarian cancer; primary tumors must be at least 50% clear cell histomorphology in order to be eligible; in addition, the tumors should be negative for expression of Wilms tumor 1 (WT-1) antigen and estrogen receptor (ER) antigen by immunohistochemistry; appropriate tissue sections to confirm stage and histologic classification of cell type must be sent to Gynecologic Oncology Group (GOG) for central pathology review; immunohistochemical stained slides for ER and WT-1 antigen must be also be submitted to GOG for pathology review
- Patients who have met the pre-entry requirements
- Patients must have signed an approved informed consent and authorization permitting release of personal health information
- Patients with a GOG performance status of 0, 1, or 2
- Patients must be entered between 2 and 12 weeks after initial surgery; performed for the combined purpose of diagnosis, staging and cytoreduction
- Patients should be free of active infection requiring antibiotics (with the exception of uncomplicated urinary tract infection [UTI])
- Absolute neutrophil count >= 1,500/mcl
- Platelets >= 100,000/mcl
- Total bilirubin within normal institutional limits
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =< 2.5 times institutional upper limit of normal (< 5 times upper limit of normal [ULN] for subjects with liver metastases)
- Alkaline phosphatase =< 2.5 times institutional upper limit of normal (< 5 times ULN for subjects with liver metastases)
- Creatinine =< 1.5 x institutional upper limit of normal, grade 1 per CTCAE v. 4.0
- Cholesterol =< 350 mg/dL (fasting)
- Triglycerides =< 400 mg/dL (fasting)
- Albumin >= 3.0 g/dL
- Prothrombin time (PT) such that international normalized ratio (INR) is =< 1.5 (or an in-range INR, usually between 2 and 3, if a patient is on a stable dose of therapeutic warfarin for management of venous thrombosis including pulmonary thrombo-embolus)
- Partial thromboplastin time (PTT) < 1.2 times the upper limit of normal
- Neurologic function (sensory and motor) =< CTCAE grade 1
- Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancer, are excluded if there is any evidence of other malignancy being present within the last five years; patients are also excluded if their previous cancer treatment contraindicates this protocol therapy
- Patients who have received prior radiotherapy to any portion of the abdominal cavity or pelvis are excluded; prior radiation for localized cancer of the breast, head and neck, or skin is permitted, provided that it was completed more than five years prior to registration, and the patient remains free of recurrent or metastatic disease
- Patients who have received prior chemotherapy for any abdominal or pelvic tumor including neo-adjuvant chemotherapy for their clear cell ovarian cancer
- Patients with primary peritoneal and fallopian tube carcinoma are not eligible
- Previous treatment with an mTOR inhibitor (sirolimus, temsirolimus, everolimus), paclitaxel, or carboplatin
- Patients cannot be receiving enzyme-inducing antiepileptic drugs (enzyme-inducing antiepileptic drugs [EIAEDs]; e.g., phenytoin, carbamazepine, phenobarbital) nor any other cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inducer such as rifampin or St. John's Wort; use of agents that potently inhibit CYP3A4 (and hence may raise temsirolimus levels), such as ketoconazole, is discouraged, but not specifically prohibited; the appropriateness of use of such agents is left to physician discretion; strong CYP3A4 inhibitors are prohibited
- Patients receiving any investigational agents
- Patients with severely impaired lung function defined as a diffusion lung capacity for carbon monoxide (DLCO) =< 50% of the normal predicted value and/or oxygen (O2) saturation =< 88% at rest on room air
- Patients with symptomatic congestive heart failure of New York Heart Association class III or IV, unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction =< 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant disease
- Patients with active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major vessels
- Patients on maintenance corticosteroids are ineligible with the exception of short term use (fewer than 5 days)
- Patients with baseline requirement for oxygen
- Patients with serious concomitant illness which, in the opinion of the treating physician, will place patient at unreasonable risk from therapy on this protocol
- Patients who are pregnant or nursing; patients of childbearing potential must agree to use contraceptive measures during study therapy and for at least six months after completion of study therapies
- Patients with poorly controlled diabetes
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Treatment (paclitaxel, carboplatin, temsirolimus, docetaxel) Laboratory Biomarker Analysis Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1 and temsirolimus IV on days 1 and 8. Treatment repeats every 3 weeks for 6 courses. Patients then receive consolidation therapy comprising temsirolimus IV on days 1, 8, and 15. Treatment repeats every 3 weeks for 11 courses in the absence of disease progression or unacceptable toxicity. NOTE: \* For circumstances in which docetaxel should be substituted for paclitaxel, docetaxel is given IV over 1 hour. Treatment (paclitaxel, carboplatin, temsirolimus, docetaxel) Docetaxel Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1 and temsirolimus IV on days 1 and 8. Treatment repeats every 3 weeks for 6 courses. Patients then receive consolidation therapy comprising temsirolimus IV on days 1, 8, and 15. Treatment repeats every 3 weeks for 11 courses in the absence of disease progression or unacceptable toxicity. NOTE: \* For circumstances in which docetaxel should be substituted for paclitaxel, docetaxel is given IV over 1 hour. Treatment (paclitaxel, carboplatin, temsirolimus, docetaxel) Carboplatin Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1 and temsirolimus IV on days 1 and 8. Treatment repeats every 3 weeks for 6 courses. Patients then receive consolidation therapy comprising temsirolimus IV on days 1, 8, and 15. Treatment repeats every 3 weeks for 11 courses in the absence of disease progression or unacceptable toxicity. NOTE: \* For circumstances in which docetaxel should be substituted for paclitaxel, docetaxel is given IV over 1 hour. Treatment (paclitaxel, carboplatin, temsirolimus, docetaxel) Paclitaxel Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1 and temsirolimus IV on days 1 and 8. Treatment repeats every 3 weeks for 6 courses. Patients then receive consolidation therapy comprising temsirolimus IV on days 1, 8, and 15. Treatment repeats every 3 weeks for 11 courses in the absence of disease progression or unacceptable toxicity. NOTE: \* For circumstances in which docetaxel should be substituted for paclitaxel, docetaxel is given IV over 1 hour. Treatment (paclitaxel, carboplatin, temsirolimus, docetaxel) Temsirolimus Patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1 and temsirolimus IV on days 1 and 8. Treatment repeats every 3 weeks for 6 courses. Patients then receive consolidation therapy comprising temsirolimus IV on days 1, 8, and 15. Treatment repeats every 3 weeks for 11 courses in the absence of disease progression or unacceptable toxicity. NOTE: \* For circumstances in which docetaxel should be substituted for paclitaxel, docetaxel is given IV over 1 hour.
- Primary Outcome Measures
Name Time Method Compare Progression-free Survival in Newly Diagnosed Stage III or IV Clear Cell Ovarian Cancer Patients in Patients in the U.S. and Worldwide (Outside of Japan) Versus Patients in Japan. Tumor scans were done every other cycle for the first 6 months;then every 3 mnths x2;then every 6 mnths thereafter; and at any other time if clinically indicated based on symptoms or physical signs suggesting progressive dx or rising serum tumor marker le Progression-free survival (PFS) was defined s the period from study entry until disease progression, death, or the last date of contact. Progression was based on Response Evaluation Criteria In Solid Tumors (RECIST) 1.1. Outcome measure data not reported because protocol stated "If the combination is declared active (i.e. HO is rejected) in one or both of the populations, the two populations will be compared with respect to PFS using a logrank test stratified by optimal/suboptimal disease status." The combination was not declared active in either population.
Proportion of Patients Who Are Alive and Progression-free for at Least 12 Months After Study Entry in Patients With Newly Diagnosed Stage III or IV Clear Cell Ovarian Cancer in the Following Populations: Patients in the U.S./Worldwide and Japan Tumor scans were done every other cycle for the first 6 months; then every 3 months x2; then every 6 months thereafter; and at any other time if clinically indicated or signs suggestive of progressive disease or rising levels; for up to 5 years. Progression of target lesions (TL) was a \>=20% increase in the sum of the diameters of TL, taking as reference the smallest sum on study (including the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must demonstrate an absolute increase \>=5 mm. Progression of non-target lesions (NTL) as defined as appearance of \>=1 new lesions or unequivocal progression of existing NTL. Unequivocal progression should not normally trump target lesion status; it must be representative of overall disease status change, not a single lesion increase. Clear progression of only NTL is exceptional, but the opinion of the treating physician should prevail in such circumstances, and the progression status should be later confirmed by a review panel (or Principal Investigator). Progression of TL, unequivocal progression of NTL, or new lesions constitutes progression. This description is abbreviated; see the RECIST 1.1 manuscript for further details.
Frequency and Severity of Toxicity Each cycle while on treatment Grade 3 or higher adverse events were graded by CTC AE v4
- Secondary Outcome Measures
Name Time Method Objective Tumor Response Every other cycle for first 6 months; then every 3 months for two years; then every six months for the next three years; and at any other time if clinically indicated based on symptoms or physical signs suggestive of progressive disease or rising serum tu Complete and Partial Tumor Response by RECIST 1.1. RECIST1.1 is a multi-page paper, and response is defined in the protocol across multiple pages, so it is not practical to define response here.
Progression-free Survival Tumor scans were done every other cycle for the first 6 months; then every 3 months x 2; then every 6 mths thereafter; and at any other time if clinically indicated based on symptoms or physical signs suggestive of progressive disease or rising tumor mark Progression-free survival (PFS) was defined as the period from study entry until disease progression, death, or the last date of contact. Progression was based on RECIST 1.1
Overall Survival Every cycle during treatment, then every 3 months for the first 2 years, then every six months for the next three years and then annually for the next 5 years. Overall survival is defined as the duration of time from study entry to time of death or the date of last contact.
Trial Locations
- Locations (145)
Cadence Cancer Center in Warrenville
🇺🇸Warrenville, Illinois, United States
Lahey Hospital and Medical Center
🇺🇸Burlington, Massachusetts, United States
Case Western Reserve University
🇺🇸Cleveland, Ohio, United States
Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
Massachusetts General Hospital Cancer Center
🇺🇸Boston, Massachusetts, United States
University of Washington Medical Center
🇺🇸Seattle, Washington, United States
Michiana Hematology Oncology PC-Niles
🇺🇸Niles, Michigan, United States
Bronson Methodist Hospital
🇺🇸Kalamazoo, Michigan, United States
Cancer Research for the Ozarks NCORP
🇺🇸Springfield, Missouri, United States
Sparrow Hospital
🇺🇸Lansing, Michigan, United States
CoxHealth South Hospital
🇺🇸Springfield, Missouri, United States
Saint Joseph Mercy Oakland
🇺🇸Pontiac, Michigan, United States
Saint Joseph Mercy Port Huron
🇺🇸Port Huron, Michigan, United States
Saint Mary Mercy Hospital
🇺🇸Livonia, Michigan, United States
Winthrop University Hospital
🇺🇸Mineola, New York, United States
Lakeland Hospital
🇺🇸Saint Joseph, Michigan, United States
Mercy Hospital-Joplin
🇺🇸Joplin, Missouri, United States
Mercy Hospital Springfield
🇺🇸Springfield, Missouri, United States
West Michigan Cancer Center
🇺🇸Kalamazoo, Michigan, United States
Saint John Macomb-Oakland Hospital
🇺🇸Warren, Michigan, United States
Saint Mary's of Michigan
🇺🇸Saginaw, Michigan, United States
Cooper Hospital University Medical Center
🇺🇸Camden, New Jersey, United States
Summa Akron City Hospital/Cooper Cancer Center
🇺🇸Akron, Ohio, United States
Korea Cancer Center Hospital
🇰🇷Seoul, Korea, Republic of
MetroHealth Medical Center
🇺🇸Cleveland, Ohio, United States
Lake University Ireland Cancer Center
🇺🇸Mentor, Ohio, United States
Stony Brook University Medical Center
🇺🇸Stony Brook, New York, United States
Carolinas Medical Center/Levine Cancer Institute
🇺🇸Charlotte, North Carolina, United States
Women and Infants Hospital
🇺🇸Providence, Rhode Island, United States
Kettering Medical Center
🇺🇸Kettering, Ohio, United States
Geisinger Medical Center
🇺🇸Danville, Pennsylvania, United States
National Kyushu Cancer Center
🇯🇵Minami-ku, Japan
Hyogo Cancer Center
🇯🇵Akashi-city, Hyogo, Japan
Indiana University/Melvin and Bren Simon Cancer Center
🇺🇸Indianapolis, Indiana, United States
Saint Vincent Oncology Center
🇺🇸Indianapolis, Indiana, United States
Women's Cancer Center of Nevada
🇺🇸Las Vegas, Nevada, United States
University of Kansas Cancer Center
🇺🇸Kansas City, Kansas, United States
University of Mississippi Medical Center
🇺🇸Jackson, Mississippi, United States
Saint Joseph's Hospital and Medical Center
🇺🇸Phoenix, Arizona, United States
University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
Providence Saint Joseph Medical Center/Disney Family Cancer Center
🇺🇸Burbank, California, United States
USC / Norris Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
Palo Alto Medical Foundation-Gynecologic Oncology
🇺🇸Mountain View, California, United States
University of Chicago Comprehensive Cancer Center
🇺🇸Chicago, Illinois, United States
Elkhart General Hospital
🇺🇸Elkhart, Indiana, United States
Community Howard Regional Health
🇺🇸Kokomo, Indiana, United States
Michiana Hematology Oncology PC-Plymouth
🇺🇸Plymouth, Indiana, United States
Michiana Hematology Oncology PC-Westville
🇺🇸Westville, Indiana, United States
Memorial Hospital of South Bend
🇺🇸South Bend, Indiana, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Marie Yeager Cancer Center
🇺🇸Saint Joseph, Michigan, United States
Oakwood Hospital and Medical Center
🇺🇸Dearborn, Michigan, United States
Allegiance Health
🇺🇸Jackson, Michigan, United States
Genesys Regional Medical Center
🇺🇸Grand Blanc, Michigan, United States
Ohio State University Comprehensive Cancer Center
🇺🇸Columbus, Ohio, United States
University of Cincinnati
🇺🇸Cincinnati, Ohio, United States
Hillcrest Hospital Cancer Center
🇺🇸Mayfield Heights, Ohio, United States
Abington Memorial Hospital
🇺🇸Abington, Pennsylvania, United States
PeaceHealth Medical Group PC
🇺🇸Bellingham, Washington, United States
Geisinger Medical Group
🇺🇸State College, Pennsylvania, United States
Geisinger Wyoming Valley/Henry Cancer Center
🇺🇸Wilkes-Barre, Pennsylvania, United States
Harrison HealthPartners Hematology and Oncology-Bremerton
🇺🇸Bremerton, Washington, United States
Pacific Gynecology Specialists
🇺🇸Seattle, Washington, United States
Group Health Cooperative-Seattle
🇺🇸Seattle, Washington, United States
Northwest Hospital
🇺🇸Seattle, Washington, United States
Saint Joseph Medical Center
🇺🇸Tacoma, Washington, United States
Olympic Medical Cancer Care Center
🇺🇸Sequim, Washington, United States
Los Angeles County-USC Medical Center
🇺🇸Los Angeles, California, United States
Saint Francis Hospital and Medical Center
🇺🇸Hartford, Connecticut, United States
The Hospital of Central Connecticut
🇺🇸New Britain, Connecticut, United States
Hartford Hospital
🇺🇸Hartford, Connecticut, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
Saint Alphonsus Cancer Care Center-Boise
🇺🇸Boise, Idaho, United States
Memorial University Medical Center
🇺🇸Savannah, Georgia, United States
Sudarshan K Sharma MD Limted-Gynecologic Oncology
🇺🇸Hinsdale, Illinois, United States
Good Samaritan Regional Health Center
🇺🇸Mount Vernon, Illinois, United States
Michiana Hematology Oncology PC-Elkhart
🇺🇸Elkhart, Indiana, United States
Saint Joseph Regional Medical Center-Mishawaka
🇺🇸Mishawaka, Indiana, United States
IU Health La Porte Hospital
🇺🇸La Porte, Indiana, United States
Michiana Hematology Oncology PC-Mishawaka
🇺🇸Mishawaka, Indiana, United States
Michiana Hematology Oncology PC-South Bend
🇺🇸South Bend, Indiana, United States
South Bend Clinic
🇺🇸South Bend, Indiana, United States
Walter Reed Army Medical Center-Olney
🇺🇸Olney, Maryland, United States
Wayne State University/Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Hurley Medical Center
🇺🇸Flint, Michigan, United States
Saint John Hospital and Medical Center
🇺🇸Detroit, Michigan, United States
Gynecologic Oncology of West Michigan PLLC
🇺🇸Grand Rapids, Michigan, United States
Borgess Medical Center
🇺🇸Kalamazoo, Michigan, United States
Cleveland Clinic Cancer Center/Fairview Hospital
🇺🇸Cleveland, Ohio, United States
Tulsa Cancer Institute
🇺🇸Tulsa, Oklahoma, United States
Geisinger Medical Center-Cancer Center Hazleton
🇺🇸Hazleton, Pennsylvania, United States
M D Anderson Cancer Center CCOP Research Base
🇺🇸Houston, Texas, United States
M D Anderson Cancer Center
🇺🇸Houston, Texas, United States
Providence Regional Cancer Partnership
🇺🇸Everett, Washington, United States
Harrison Medical Center
🇺🇸Bremerton, Washington, United States
Skagit Valley Hospital Regional Cancer Care Center
🇺🇸Mount Vernon, Washington, United States
Harrison HealthPartners Hematology and Oncology-Poulsbo
🇺🇸Poulsbo, Washington, United States
Fred Hutchinson Cancer Research Center
🇺🇸Seattle, Washington, United States
Seattle Cancer Care Alliance
🇺🇸Seattle, Washington, United States
Rockwood Cancer Treatment Center-DHEC-Downtown
🇺🇸Spokane, Washington, United States
Swedish Medical Center-First Hill
🇺🇸Seattle, Washington, United States
Cancer Care Northwest - Spokane South
🇺🇸Spokane, Washington, United States
Wenatchee Valley Hospital and Clinics
🇺🇸Wenatchee, Washington, United States
Providence Saint Mary Regional Cancer Center
🇺🇸Walla Walla, Washington, United States
Tohoku University School of Medicine
🇯🇵Sendai, Aoba-ku, Japan
University of the Ryukyus Hospital-Col Health Scnc
🇯🇵Nakagami-gun, Okinawa, Japan
Iwate Medical University School of Medicine
🇯🇵Morioka, Iwate, Japan
Kagoshima City Hospital
🇯🇵Kagoshima City, Kagoshima, Japan
Shizuoka Cancer Center
🇯🇵Shizuoka City, Suntou, Japan
Niigata University Medical and Dental Hospital
🇯🇵Niigata City, Niigata, Japan
Shikoku Cancer Center
🇯🇵Matsuyama, Japan
Jikei University School of Medicine
🇯🇵Minato-ku, Tokyo, Japan
Kinki University
🇯🇵Osaka, Osaka, Japan
National Cancer Center Hospital
🇯🇵Tokyo, Japan
Tottori University
🇯🇵Tottori, Japan
Keimyung University-Dongsan Medical Center
🇰🇷Jung-Ku, Daegu, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Korea, Republic of
Gangnam Severance Hospital
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Elkhart Clinic
🇺🇸Elkhart, Indiana, United States
MultiCare Tacoma General Hospital
🇺🇸Tacoma, Washington, United States
National Cancer Center-Korea
🇰🇷Goyang-si, Gyeonggi-do, Korea, Republic of
Northern Indiana Cancer Research Consortium CCOP
🇺🇸South Bend, Indiana, United States
Baystate Medical Center
🇺🇸Springfield, Massachusetts, United States
Kure National Hospital
🇯🇵Kure, Hiroshima, Japan
Hokkaido University Hospital
🇯🇵Sapporo, Hokkaido, Japan
Saitama Medical University International Medical Center
🇯🇵Saitama, Japan
Keio University
🇯🇵Shinjuku-ku, Tokyo, Japan
University of Colorado Cancer Center - Anschutz Cancer Pavilion
🇺🇸Aurora, Colorado, United States
Florida Hospital Orlando
🇺🇸Orlando, Florida, United States
Iowa Methodist Medical Center
🇺🇸Des Moines, Iowa, United States
Iowa Oncology Research Association CCOP
🇺🇸Des Moines, Iowa, United States
Medical Oncology and Hematology Associates-Des Moines
🇺🇸Des Moines, Iowa, United States
Medical Oncology and Hematology Associates-Laurel
🇺🇸Des Moines, Iowa, United States
Mercy Medical Center - Des Moines
🇺🇸Des Moines, Iowa, United States
Iowa Lutheran Hospital
🇺🇸Des Moines, Iowa, United States
Saint Joseph Mercy Hospital
🇺🇸Ann Arbor, Michigan, United States
Michigan Cancer Research Consortium CCOP
🇺🇸Ann Arbor, Michigan, United States
Nebraska Methodist Hospital
🇺🇸Omaha, Nebraska, United States
University of North Carolina at Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
Wake Forest University Health Sciences
🇺🇸Winston-Salem, North Carolina, United States
University of Wisconsin Hospital and Clinics
🇺🇸Madison, Wisconsin, United States
Froedtert and the Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States