Tumor-Agnostic Precision Immuno-Oncology and Somatic Targeting Rational for You (TAPISTRY) Platform Study

Sponsor

Hoffmann-La Roche (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04589845

Collaborator

(none)

770

Enrollment

150

Locations

Arms

140.2

Anticipated Duration (Months)

5.1

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

TAPISTRY is a Phase II, global, multicenter, open-label, multi-cohort study designed to evaluate the safety and efficacy of targeted therapies or immunotherapy as single agents or in rational, specified combinations in participants with unresectable, locally advanced or metastatic solid tumors determined to harbor specific oncogenic genomic alterations or who are tumor mutational burden (TMB)-high as identified by a validated next-generation sequencing (NGS) assay. Participants with solid tumors will be treated with a drug or drug regimen tailored to their NGS assay results at screening. Participants will be assigned to the appropriate cohort based on their genetic alteration(s). Treatment will be assigned on the basis of relevant oncogenotype, will have cohort-specific inclusion/exclusion criteria, and, unless otherwise specified, will continue until disease progression, loss of clinical benefit, unacceptable toxicity, participant or physician decision to discontinue, or death, whichever occurs first.

Condition or Disease	Intervention/Treatment	Phase
Solid Tumors	Drug: Entrectinib Drug: Entrectinib Drug: Alectinib Drug: Atezolizumab Drug: Ipatasertib Drug: Trastuzumab emtansine Drug: Idasanutlin Drug: Inavolisib Drug: Belvarafenib Drug: Pralsetinib	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

770 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Tumor-Agnostic Precision Immunooncology and Somatic Targeting Rational for You (TAPISTRY) Phase II Platform Trial

Actual Study Start Date :

Jan 18, 2021

Anticipated Primary Completion Date :

Sep 25, 2032

Anticipated Study Completion Date :

Sep 25, 2032

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort A: ROS1 fusion-positive tumors Participants with metastatic or advanced solid tumors, with the exception of NSCLC will receive entrectinib once daily in repeated 28-day cycles at a dose of 600 milligram per day (mg/day) for adults and pediatric participants with a body surface area (BSA) >/= 1.51 squaremeter (m2). The total dose of daily entrectinib administration for pediatric participants with BSA<1.51 m2 will be lower.	Drug: Entrectinib Adults and pediatric participants with a BSA >/= 1.51 m2: entrectinib will be self-administered by participants orally at home at a dose of 600 mg/day (three 200-mg capsules per day). Pediatric participants with a BSA < 1.51 m2: entrectinib will be administered orally at home in mini-tablet formulation at a dose of 400 mg/day (BSA=1.11-1.50 m2) or 300 mg/day (BSA=0.81-1.10 m2) or 200 mg/day (BSA=0.51-0.80 m2) or 100 mg/day (BSA=0.43-0.50 m2). Other Names: Rozlytrek
Experimental: Cohort B: NTRK1/2/3 fusion-positive tumors Participants with metastatic or advanced solid tumors will receive entrectinib once daily in repeated 28-day cycles at a dose of 600 mg/day for adults and pediatric participants with a BSA >/= 1.51 m2. The total dose of daily entrectinib administration for pediatric participants with BSA<1.51 m2 will be lower.	Drug: Entrectinib Adults and pediatric participants with a BSA >/= 1.51 m2: entrectinib will be self-administered by participants orally at home at a dose of 600 mg/day (three 200-mg capsules per day). Pediatric participants with a BSA < 1.51 m2: entrectinib will be administered orally at home in mini-tablet formulation at a dose of 400 mg/day (BSA=1.11-1.50 m2) or 300 mg/day (BSA=0.81-1.10 m2) or 200 mg/day (BSA=0.51-0.80 m2) or 100 mg/day (BSA=0.43-0.50 m2). Other Names: Rozlytrek
Experimental: Cohort C: ALK fusion-positive tumors Participants with metastatic or advanced solid tumors, with the exception of NSCLC, will receive alectinib at a dosage of 600 mg orally twice a day (BID), taken with food, in repeated 28-day cycles.	Drug: Alectinib Alectinib will be administered orally BID (twice a day) with food at a dosage of 600 mg (four 150-mg capsules). Other Names: Alecensa
Experimental: Cohort D: TMB-high tumors Participants with metastatic or advanced solid tumors will receive atezolizumab intravenously (IV) at a fixed dose for participants aged >/= 18 years, and 15 mg/kg (maximum 1200 mg) for participants aged < 18 years on Day 1 of each 21-day cycle.	Drug: Atezolizumab Atezolizumab will be administered by IV infusion at a fixed dose of 1200 mg for participants aged >/=18 years, and 15 mg/kg (maximum 1200 mg) for participants aged <18 years on Day 1 of each 21-day cycle. Other Names: Tecentriq
Experimental: Cohort E: AKT1/2/3 mutant-positive tumors Participants with metastatic or advanced solid tumors will receive ipatasertib orally once daily (QD) at the starting dose of 400 mg in repeated 28-day cycles until the participant experiences disease progression, intolerable toxicity, or withdraws consent. For participants 12-17 years of age, ipatasertib will be administered at the starting dose of 200 mg for participants <35 kg, 300 mg for participants >/= 35 and <45 kg, 400 mg for those >/=45 kg orally QD in repeated 28-day cycles until the participant experiences disease progression, intolerable toxicity, or withdraws consent.	Drug: Ipatasertib For participants 12-17 years of age, ipatasertib will be administered at the starting dose of 200 mg for participants < 35 kg, 300 mg for participants >/= 35 and < 45 kg, 400 mg for those >/= 45 kg orally QD, beginning of Cycle 1, on Days 1-21 of each 28-day cycle until the participant experiences disease progression, intolerable toxicity, or withdraws consent.
Experimental: Cohort F: HER2 mutant-positive tumors Participants with metastatic or advanced solid tumors will receive trastuzumab emtansine IV at a dose of 3.6 mg/kg every 21 days.	Drug: Trastuzumab emtansine Trastuzumab emtansine will be administered at 3.6 mg/kg by IV infusion every 21 days until disease progression or unacceptable toxicity. The dosage and administration method also applies for pediatric participants 12-17 years of age. Other Names: Kadcyla
Experimental: Cohort G: MDM2-amplified, TP53 wild-type tumors Participants with metastatic or advanced solid tumors will receive idasanutlin at a dose of 250 mg orally QD on Days 1-5 of each 28-day cycle. Note: Cohort G has been closed for enrollment	Drug: Idasanutlin Idasanutlin will be administered at 250 mg QD (daily) PO for Days 1-5 of each 28-day cycle. Idasanutlin may be given without regard to meals and water can be given as often as necessary or desired. The daily doses should be administered 10-14 hours apart. Note: Cohort G has been closed for enrollment.
Experimental: Cohort H: PIK3CA multiple mutant-positive tumors Participants with metastatic or advanced solid tumors will receive GDC-0077 QD at a starting dose of 9 mg by mouth (PO) in repeated 28-day cycles.	Drug: Inavolisib GDC-077 will be administered QD at a starting dose of 9 mg PO in repeated 28-day cycles. The dosage and administration method also applies for pediatric participants 12-17 years of age. Other Names: GDC-0077
Experimental: Cohort I: BRAF class II mutant or fusion-positive tumors Participants with BRAF class II mutant/fusion-positive tumors (adults and adolescents ≥ 40 kg) will receive 400 mg belvarafenib by mouth (PO) BID (twice a day) with adequate water (more than 200 mL). One cycle consists of 28 days. Administration of belvarafenib should occur BID on every day of each 28-day cycle.	Drug: Belvarafenib Belvarafenib will be administered at a dose 400 mg (PO) BID with adequate water (more than 200 mL). One cycle consists of 28 days. Administration of belvarafenib should occur BID on every day of each 28-day cycle.
Experimental: Cohort J: BRAF class III mutant-positive tumors Participants with BRAF class III mutant-positive tumors(adults and adolescents ≥ 40 kg) will receive 400 mg belvarafenib by mouth (PO) BID (twice a day) with adequate water (more than 200 mL). One cycle consists of 28 days. Administration of belvarafenib should occur BID on every day of each 28-day cycle.	Drug: Belvarafenib Belvarafenib will be administered at a dose 400 mg (PO) BID with adequate water (more than 200 mL). One cycle consists of 28 days. Administration of belvarafenib should occur BID on every day of each 28-day cycle.
Experimental: Cohort K: RET fusion-positive tumors Participants with RET fusion-positive tumors will self-administer Pralsetinib orally at home (except on clinic days) on a continuous daily dosing regimen at a dose of 400 mg/day (four 100-mg capsules per day) for adult and pediatric patients ≥ 12 and < 18 years of age. A treatment cycle consists of 4 weeks (28 days).	Drug: Pralsetinib Pralsetinib will be self-administered by participants orally at home (except on clinic days) on a continuous daily dosing regimen at a dose of 400 mg/day (four 100-mg capsules per day) for adult and pediatric patients ≥ 12 and < 18 years of age. A treatment cycle consists of 4 weeks (28 days). Other Names: Gavreto (US)

Outcome Measures

Primary Outcome Measures

All Cohorts: Independent Review Committee (IRC)-assessed objective response rate (ORR) based on confirmed objective response (OR) per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) [Approximately up to 12 years]
Confirmed objective response indicates >/= 4 weeks after initial documentation of response

Secondary Outcome Measures

All Cohorts: IRC-assessed duration of response (DOR) per RECIST v1.1 [Approximately up to 12 years]
All Cohorts: IRC-assessed clinical benefit rate (CBR) per RECIST v1.1 [Approximately up to 12 years]
All Cohorts: IRC-assessed progression free survival (PFS) per RECIST v1.1 [Approximately up to 12 years]
All Cohorts: Investigator (INV)-assessed ORR per RECIST v1.1 [Approximately up to 12 years]
All Cohorts: INV-assessed DOR per RECIST v1.1 [Approximately up to 12 years]
All Cohorts: INV-assessed CBR per RECIST v1.1 [Approximately up to 12 years]
All Cohorts: INV-assessed PFS per RECIST v1.1 [Approximately up to 12 years]
All Cohorts: IRC- and INV-assessed time to central nervous system (CNS) progression per RECIST v1.1 [Approximately up to 12 years]
All Cohorts: Overall Survival (OS) [Approximately up to 12 years]
Cohorts A, B, C, D, I, J, K: IRC-assessed CNS-ORR per Response Assessment in Neuro-Oncology (RANO) [Approximately up to 12 years]
Cohorts A, B, C, D, I, J, K: IRC-assessed CNS-DOR per RANO [Approximately up to 12 years]
Cohorts A, B, C, D, I, J, K: IRC-assessed CNS-CBR per RANO [Approximately up to 12 years]
Cohorts A, B, C, D, I, J, K: IRC-assessed CNS-PFS per RANO [Approximately up to 12 years]
Cohorts A, B, C, D, I, J, K: INV-assessed CNS-ORR per RANO [Approximately up to 12 years]
Cohorts A, B, C, D, I, J, K: INV-assessed CNS-DOR per RANO [Approximately up to 12 years]
Cohorts A, B, C, D, I, J, K: INV-assessed CNS-CBR per RANO [Approximately up to 12 years]
Cohorts A, B, C, D, I, J, K: INV-assessed CNS-PFS per RANO [Approximately up to 12 years]
Cohorts A, B, D, E, F, H, I, J, K: IRC-assessed ORR per International Neuroblastoma Response Criteria (INRC) [Approximately up to 12 years]
Cohorts A, B, D, E, F, H, I, J, KIRC-assessed DOR per INRC [Approximately up to 12 years]
Cohorts A, B, D, E, F, H, I, J, K: IRC-assessed CBR per INRC [Approximately up to 12 years]
Cohorts A, B, D, E, F, H, I, J, K: IRC-assessed PFS per INRC [Approximately up to 12 years]
Cohorts A, B, D, E, F, H, I, J, K: INV-assessed ORR per INRC [Approximately up to 12 years]
Cohorts A, B, D, E, F, H, I, J, K: INV-assessed DOR per INRC [Approximately up to 12 years]
Cohorts A, B, D, E, F, H, I, J, K: INV-assessed CBR per INRC [Approximately up to 12 years]
Cohorts A, B, D, E, F, H, I, J, K: INV-assessed PFS per INRC [Approximately up to 12 years]
All Cohorts: IRC-assessed ORR per RECIST v1.1 in participants with alteration/biomarker-positive circulating tumor DNA (ctDNA) by blood-based next-generation sequencing (NGS) assay [Approximately up to 12 years]
All Cohorts: IRC-assessed DOR per RECIST v1.1 in participants with alteration/biomarker-positive ctDNA by blood-based NGS assay [Approximately up to 12 years]
All Cohorts: IRC-assessed CBR per RECIST v1.1 in participants with alteration/biomarker-positive ctDNA by blood-based NGS assay [Approximately up to 12 years]
All Cohorts: IRC-assessed PFS per RECIST v1.1 in participants with alteration/biomarker-positive ctDNA by blood-based NGS assay [Approximately up to 12 years]
All Cohorts: INV-assessed ORR per RECIST v1.1 in participants with alteration/biomarker-positive ctDNA by blood-based NGS assay [Approximately up to 12 years]
All Cohorts: INV-assessed DOR per RECIST v1.1 in participants with alteration/biomarker-positive ctDNA by blood-based NGS assay [Approximately up to 12 years]
All Cohorts: INV-assessed CBR per RECIST v1.1 in participants with alteration/biomarker-positive ctDNA by blood-based NGS assay [Approximately up to 12 years]
All Cohorts: INV-assessed PFS per RECIST v1.1 in participants with alteration/biomarker-positive ctDNA by blood-based NGS assay [Approximately up to 12 years]
Cohorts A, B, C, D, I, J, K: IRC-assessed intracranial (IC)-ORR per RECIST v1.1 [Approximately up to 12 years]
Cohorts A, B, C, D, I, J, K: IRC-assessed IC-DOR per RECIST v1.1 [Approximately up to 12 years]
Cohorts A, B, C, D, I, J, K: IRC-assessed IC-CBR per RECIST v1.1 [Approximately up to 12 years]
Cohorts A, B, C, D, I, J, K: IRC-assessed IC-PFS rate per RECIST v1.1 [Approximately up to 12 years]
Cohorts A, B, C, D, I, J, K: INV-assessed IC-ORR per RECIST v1.1 [Approximately up to 12 years]
Cohorts A, B, C, D, I, J, K: INV-assessed IC-DOR per RECIST v1.1 [Approximately up to 12 years]
Cohorts A, B, C, D, I, J, K: INV-assessed IC-CBR per RECIST v1.1 [Approximately up to 12 years]
Cohorts A, B, C, D, I, J, K: INV-assessed IC-PFS rate per RECIST v1.1 [Approximately up to 12 years]
All Cohorts: Percentage of participants with confirmed deterioration as assessed by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) [Approximately up to 12 years]
The EORTC QLQ-C30 is a validated, reliable self-report measure. It consists of 30 questions that assess five aspects of participant functioning (physical, emotional, role, cognitive, and social), eight symptom scales (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea) and global health/quality of life, with a recall period of the previous week. Scale scores can be obtained for the multi-item scales using rating scales of 4 or 7 points.
All Cohorts: Change from Baseline in the EORTC-QLQ-C30 total score [Approximately up to 12 years]
All Cohorts: Percentage of participants with a clinical meaningful change on the Global Health Status, Physical Functioning, and Role Functioning scores from the EORTC QLQ-C30 [Approximately up to 12 years]
All Cohorts: Time to confirmed symptom onset or worsening from tumor-related symptom scores from the EORTC QLQ-C30 and EORTC Item Library [Approximately up to 12 years]
The EORTC Item library includes stand-alone symptoms scales and an overall assessment of treatment bother to provide additional information not currently captured in the EORTC QLQ-C30. The scales use the same rating scale and recall period of previous week as the symptom scales in the EORTC QLQ-C30.
All Cohorts: Percentage of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [Approximately up to 12 years]
Adverse event severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5 (NCI CTCAE v5.0.)
Cohorts A, B: Plasma concentration of entrectinib at specified timepoints [Day 1 of Cycle 1-6 and Day 1 of every other Cycle going forward (one Cycle=28 days)]
Cohort C: Plasma concentration of alectinib at specified timepoints [Cycle 1, Day 1 and Day 15; Day 1 of Cycle 2-6, and Day 1 of every other Cycle going forward (one Cycle=28 days)]
Cohort D: Plasma concentration of atezolizumab at specified timepoints [Day 1 of Cycle 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, and every even Cycles thereafter (one Cycle=21 days)]
Cohort E: Plasma concentration of ipatasertib at specified timepoints [Cycle 1, Day 1 and 15; Cycle 2, Day 1; Cycle 3, Day 15; Cycle 4, Day 1, and every even Cycle thereafter (one Cycle=28 days)]
Cohort F: Serum concentration of trastuzumab emtansine at specified timepoints [Cycle 1, Day 1; Cycle 2, Day 1; Cycle 4, Day 1; Cycle 6, Day 1, and every even Cycle thereafter (one Cycle=21 days)]
Cohort G: Plasma concentration of idasanutlin at specified timepoint [Cycle 1, Day 1, 2, 5, 8; Cycle 2, Day 1, 2, 5; Cycle 3, Day 2, 5; Cycle 4, Day 1, and every other Cycle going forward (one Cycle=28 days)]
Cohort H: Plasma concentration of GDC-0077 at specified timepoints [Cycle 1, Day 1, 8 (+/-1 day), 15 (+/-1 day); Cycle 2, Day 1 (+/-1 day); Day 1 of Cycle 4, and every other even Cycle going forward (one Cycle=28 days)]
Cohorts D, F: Percentage of participants with anti-drug antibodies (ADA) [Cohort D: Day 1 of Cycle 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, and every even Cycles thereafter (one Cycle=21 days); Cohort F: Cycle 1, Day 1; Cycle 2, Day 1; Cycle 4, Day 1; Cycle 6, Day 1, and every even Cycle thereafter (one Cycle=21 days)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically or cytologically confirmed diagnosis of advanced and unresectable or metastatic solid malignancy
Measurable disease as defined by Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1), Response Assessment in Neuro-Oncology (RANO) criteria, or International Neuroblastoma Response Criteria (INRC)
Performance status as follows: Participantss aged >= 18 years: Eastern Cooperative

Oncology Group (ECOG) Performance Status 0-2; Participantss aged 16 to < 18 years:

Karnofsky score >= 50%; Participants aged < 16 years: Lansky score >= 50%

For participants aged >= 18 and <18 years: adequate hematologic and end-organ function
Disease progression on prior treatment, or previously untreated disease with no available acceptable treatment
Adequate recovery from most recent systemic or local treatment for cancer
Life expectancy >= 8 weeks
Ability to comply with the study protocol, in the investigator's judgment
For female participants of childbearing potential: Negative serum pregnancy test <= 14 days prior to initiating study treatment; agreement to remain abstinent or use single or combined contraception methods that result in a failure rate of < 1% per year for the period defined in the cohort-specific inclusion criteria; and agreement to refrain from donating eggs during the same period
For male participants: Willingness to remain abstinent or use acceptable methods of contraception as defined in the cohort-specific inclusion criteria
In addition to the general inclusion criteria above, participants must meet all of the cohort-specific inclusion criteria for the respective cohort

Exclusion Criteria:

Current participation or enrollment in another therapeutic clinical trial
Any anticancer treatment within 2 weeks or 5 half-lives prior to start of study treatment
Whole brain radiotherapy within 14 days prior to start of study treatment
Stereotactic radiosurgery within 7 days prior to start of study treatment
Pregnant or breastfeeding, or intending to become pregnant during the study
History of or concurrent serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the participant's safe participation in and completion of the study or confounds the ability to interpret data from the study
Incomplete recovery from any surgery prior to the start of study treatment that would interfere with the determination of safety or efficacy of study treatment
Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or higher), myocardial infarction, or cerebrovascular accident within 3 months prior to enrollment, unstable arrhythmias, or unstable angina
History of another active cancer within 5 years prior to screening that may interfere with the determination of safety or efficacy of study treatment with respect to the qualifying solid tumor malignancy
In addition to the general exclusion criteria above, in order to be enrolled in a treatment cohort of the study, participants must not meet any of the cohort-specific exclusion criteria

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Southern Cancer Center	Daphne	Alabama	United States	36526
2	Western Regional Medical Center at Cancer Treatment Centers of America	Goodyear	Arizona	United States	85338
3	City of Hope National Medical Center	Duarte	California	United States	91010
4	Kaiser Permanente Los Angeles; Clinic/Infusion -LA	Los Angeles	California	United States	90027
5	USC Norris Cancer Center	Los Angeles	California	United States	90033
6	Hoag Memorial Hospital	Newport Beach	California	United States	92658
7	UC Davis Comprehensive Cancer Center	Sacramento	California	United States	95817
8	University of California at San Francisco	San Francisco	California	United States	94115
9	Sarcoma Oncology Center	Santa Monica	California	United States	90403
10	Christiana Care Health Srvcs; Helen F Graham Can Center	Newark	Delaware	United States	19713
11	University of Florida	Gainesville	Florida	United States	32607
12	Miami Cancer Institute of Baptist Health, Inc.	Miami	Florida	United States	33176
13	Ocala Oncology Center	Ocala	Florida	United States	34471
14	University Cancer & Blood Center, LLC; Research	Athens	Georgia	United States	30607
15	St. Alphonsus	Boise	Idaho	United States	83706
16	Midwestern Regional Med Center	Zion	Illinois	United States	60099
17	Horizon Oncology Research, Inc.	Lafayette	Indiana	United States	47905
18	New England Cancer Specialists	Scarborough	Maine	United States	04074
19	Maryland Hematology & Oncology. P.A.	Silver Spring	Maryland	United States	20904
20	St. Joseph Mercy Hospital	Ann Arbor	Michigan	United States	48106
21	Henry Ford Health System	Detroit	Michigan	United States	48202
22	University of Minnesota	Minneapolis	Minnesota	United States	55455
23	Metro-Minnesota Community Oncology Research Consortium	Saint Louis Park	Minnesota	United States	55416
24	Washington University	Saint Louis	Missouri	United States	63128
25	St. Vincent Frontier Cancer Center	Billings	Montana	United States	59101
26	Comprehensive Cancer Centers of Nevada - Eastern Avenue	Las Vegas	Nevada	United States	89169
27	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey	United States	08901
28	University of New Mexico; Comprehensive Cancer Center	Albuquerque	New Mexico	United States	87131
29	Montefiore Einstein Center for Cancer Care	Bronx	New York	United States	10461
30	Eastchester Center for Cancer Care	Bronx	New York	United States	10469
31	New York Cancer and Blood Specialists - Setauket Medical Oncology	East Setauket	New York	United States	11733
32	National Translational Research Group	New York	New York	United States	10028
33	Icahn School of Medicine at Mount Sinai	New York	New York	United States	10029
34	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
35	Levine Cancer Institute	Charlotte	North Carolina	United States	28204
36	Barrett Cancer Center	Cincinnati	Ohio	United States	45219
37	Oncology Hematology Care Inc	Cincinnati	Ohio	United States	45242
38	Providence Portland Medical Center	Portland	Oregon	United States	97213
39	Consultants in Medical Oncology and Hematology	Broomall	Pennsylvania	United States	19008
40	Alliance Cancer Specialists	Horsham	Pennsylvania	United States	19044
41	Cancer Treatment Centers of America; Eastern Regional Medical Center	Philadelphia	Pennsylvania	United States	19124
42	PRISMA Health - Greenville	Greenville	South Carolina	United States	29605
43	The West Clinic; West Cancer Center	Germantown	Tennessee	United States	38138
44	St. Jude Children'S Research Hospital	Memphis	Tennessee	United States	38105
45	Texas Onc-Central Austin CA Ct	Austin	Texas	United States	78731
46	Mary Crowley Medical Research Center	Dallas	Texas	United States	75230
47	Texas Oncology - Baylor Charles A. Sammons Cancer Center	Dallas	Texas	United States	75246
48	Cook Childrens Medical Center	Fort Worth	Texas	United States	76104
49	The University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030-4009
50	Texas Oncology, P.A. - Tyler; Tyler Cancer Center	Tyler	Texas	United States	75702
51	Virginia Cancer Specialists - Leesburg	Leesburg	Virginia	United States	20176
52	Northwest Medical Specialties, PLLC; Research Department	Tacoma	Washington	United States	98405
53	Froedtert and The Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226
54	Kinghorn Cancer Centre; St Vincents Hospital	Darlinghurst	New South Wales	Australia	2010
55	Sydney Children's Hospital	Randwick	New South Wales	Australia	2031
56	Princess Alexandra Hospital	Woolloongabba	Queensland	Australia	4102
57	Peter MacCallum Cancer Centre; Medical Oncology	Melbourne	Victoria	Australia	3000
58	Royal Children's Hospital	Parkville	Victoria	Australia	3052
59	Cliniques Universitaires St-Luc	Bruxelles		Belgium	1200
60	GHdC Site Notre Dame	Charleroi		Belgium	6000
61	UZ Antwerpen	Edegem		Belgium	2650
62	UZ Gent	Gent		Belgium	9000
63	UZ Leuven Gasthuisberg	Leuven		Belgium	3000
64	Hospital Sírio-Libanês	Sao Paulo	SP	Brazil	01308-050
65	Hospital A. C. Camargo; Oncologia	Sao Paulo	SP	Brazil	01509-010
66	Clínica Onco Star - Rede D'Or	Sao Paulo	SP	Brazil	04543-000
67	BC Cancer - Vancouver	Vancouver	British Columbia	Canada	V5Z 4E6
68	London Health Sciences Centre · Victoria Hospital; Department of Medicine	London	Ontario	Canada	N6A 5W9
69	The Ottawa Hospital - General Campus	Ottawa	Ontario	Canada	K1H 8L6
70	The Hospital for Sick Children	Toronto	Ontario	Canada	M5G 1X8
71	Princess Margaret Cancer Center	Toronto	Ontario	Canada	M5G 2M9
72	McGill University Health Center	Montreal	Quebec	Canada	H4A 3J1
73	Beijing Children's Hospital, Capital Medical University; Oncological Surgery Department	Beijing City		China	100032
74	Beijing Cancer Hospital	Beijing		China	100142
75	The First Hospital of Jilin University	Changchun City		China	130021
76	Jilin Cancer Hospital	Changchun		China	132013
77	West China Hospital - Sichuan University	Chengdu City		China	610047
78	Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine	Shanghai		China	200092
79	Shanghai East Hospital	Shanghai		China
80	Tianjin Cancer Hospital	Tianjin		China	300060
81	First Affiliated Hospital of Medical College of Xi'an Jiaotong University	Xi'an		China	710061
82	Rigshospitalet; Onkologisk Klinik	København Ø		Denmark	2100
83	Institut Bergonie; Oncologie	Bordeaux		France	33076
84	Centre Oscar Lambret; Service de Pediatrie	Lille		France	59020
85	CENTRE LEON BERARD; Département d'Hématologie et d'Oncologie	Lyon		France	69373
86	Hopital de la Timone	Marseille		France	13005
87	Institut Universitaire du Cancer de Toulouse-Oncopole	Toulouse		France	31059
88	Institut de Cancerologie Gustave-Roussy (IGR)	Villejuif		France	94805
89	Uniklinik Essen	Essen		Germany	45122
90	Georg-August-Uniklinik ; Zentrum Innere Medizin Abt. Hämatologie & Onkologie	Göttingen		Germany	37075
91	Universitätsklinikum Hamburg-Eppendorf Onkologisches Zentrum Medizinische Klinik II	Hamburg		Germany	20246
92	Medizinische Hochschule Zentrum Innere Medizin Abt.Gastroenterologie, Endokrinologie und Hepatologie	Hannover		Germany	30625
93	SLK-Kliniken Heilbronn GmbH; Klinik für Innere Medizin III; Schwerpunkt Häma./Onko./Palliativm.	Heilbronn		Germany	74078
94	Praxis für Hämatologie, Onkologie und Palliativmedizin	Mönchengladbach		Germany	41066
95	Klinikum der Universität München, Campus Großhadern; Medizinische Klinik und Poliklinik III	München		Germany	81377
96	Uniklinikum, Comprehensive Cancer Center Mainfranken; Interdisziplinäres Studienzentrum mit ECTU	Würzburg		Germany	97078
97	Hong Kong Children's Hospital	Hong Kong		Hong Kong
98	Prince of Wales Hospital; Department of Clinical Onocology	Shatin		Hong Kong
99	Rambam Health Care Campus; Oncology	Haifa		Israel	3109601
100	Hadassah University Hospital - Ein Kerem	Jerusalem		Israel	9112001
101	Rabin MC; Davidof Center - Oncology Institute	Petach Tikva		Israel	4941492
102	Sheba Medical Center	Ramat Gan		Israel	5262100
103	Sourasky / Ichilov Hospital; Dept. of Oncology	Tel Aviv		Israel	6423906
104	Istituto Nazionale Tumori Fondazione G. Pascale	Napoli	Campania	Italy	80131
105	Ospedale Pediatrico Bambino Gesù - IRCCS; Dipartimento di Onco-Ematologia Pediatrica	Roma	Lazio	Italy	00165
106	Policlinico Universitario Agostino Gemelli IRCCS; UOS Fase 1	Roma	Lazio	Italy	00168
107	Asst Degli Spedali Civili Di Brescia	Brescia	Lombardia	Italy	25123
108	Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 1	Milano	Lombardia	Italy	20133
109	Istituto Nazionale Tumori di Milano; S.C. Oncologia Pediatrica	Milano	Lombardia	Italy	20133
110	Dipartimento di Scienze Pediatriche Adolescenza; Osp. Infantile Regina Margherita	Torino	Piemonte	Italy	10126
111	Azienda Ospedaliera Meyer; Centro di Eccellenza di Oncologia ed Ematologia Pediatrica	Firenze	Toscana	Italy	50139
112	Azienda Ospedaliera Universitaria Senese, U.O.C. Immunoterapia Oncologica	Siena	Toscana	Italy	53100
113	National Cancer Center Hospital East	Chiba		Japan	277-8577
114	Kindai University Hospital	Osaka		Japan	589-8511
115	National Cancer Center Hospital	Tokyo		Japan	104-0045
116	Seoul National University Bundang Hospital	Seongnam-si		Korea, Republic of	13605
117	Seoul National University Hospital- Adult Site	Seoul		Korea, Republic of	03080
118	Seoul National University Hospital- Pediatric Site	Seoul		Korea, Republic of	03080
119	Severance Hospital, Yonsei University Health System	Seoul		Korea, Republic of	03722
120	Asan Medical Center	Seoul		Korea, Republic of	05505
121	Samsung Medical Center- Adult Site	Seoul		Korea, Republic of	06351
122	Samsung Medical Center- Pediatric Site	Seoul		Korea, Republic of	06351
123	Prinses Maxima Centrum	Utrecht		Netherlands	3584 CS
124	Auckland City Hospital, Cancer and Blood Research	Auckland		New Zealand	1023
125	Christchurch Hospital; Dept of Oncology	Christchurch		New Zealand
126	Uniwersyteckie Centrum Kliniczne, Klinika Onkologii i Radioterapii	Gdansk		Poland	80-214
127	Narod.Inst.Onkol. im. M.Sklodowskiej - Curie-Panst.Inst.Bad; Klinika Nowot.Pluca i Klatki Piers	Warszawa		Poland	02-781
128	IPO do Porto; Servico de Oncologia Medica	Porto		Portugal	4200-072
129	PanOncology Trials; Hospital Oncológico, Puerto Rico Medical Center	San Juan		Puerto Rico	00935
130	National University Hospital; National University Cancer Institute, Singapore (NCIS)	Singapore		Singapore	119228
131	National Cancer Centre; Medical Oncology	Singapore		Singapore	169610
132	Hospital Sant Joan De Deu	Esplugues De Llobregas	Barcelona	Spain	08950
133	Vall d´Hebron Institute of Oncology (VHIO), Barcelona	Barcelona		Spain	08035
134	Hospital Infantil Universitario Nino Jesus	Madrid		Spain	28009
135	Clinica Universidad de Navarra Madrid; Servicio de Oncología	Madrid		Spain	28027
136	START Madrid-FJD, Hospital Fundacion Jimenez Diaz	Madrid		Spain	28040
137	Hospital Universitario 12 de Octubre; Servicio de Oncologia	Madrid		Spain	28041
138	Hospital Universitario La Paz; Servicio de Oncologia	Madrid		Spain	28046
139	START Madrid. Centro Integral Oncologico Clara Campal; CIOCC	Madrid		Spain	28050
140	Hospital Universitario la Fe; Servicio de Oncologia	Valencia		Spain	46026
141	Ospedale Regionale di Bellinzona Medizin Onkologie	Bellinzona		Swaziland	6500
142	Universitätsspital Basel (USB)	Basel		Switzerland	4031
143	Inselspital, Klinik und Poliklinik für Medizinische Onkologie	Bern		Switzerland	3012
144	Unversitätsspital Zürich	Zürich		Switzerland	8091
145	National Cheng Kung University Hospital; Oncology	Tainan		Taiwan	00704
146	Taipei Veterans General Hospital; Department of Oncology	Taipei City		Taiwan	112201
147	Chang Gung Memorial Hospital-Linkou; Dept of Oncology	Taoyuan County		Taiwan	333
148	National Taiwan University Hospital; Oncology	Zhongzheng Dist.		Taiwan	10048
149	University College London Hospital	London		United Kingdom	NW1 - 2PG
150	The Christie NHS Foundation Trust	Manchester		United Kingdom	M20 4BX