Clinical trial NCT03709680: Study Of Palbociclib Combined With Chemotherapy In Pediatric Patients With Recurrent/Refractory Solid Tumors
Official title: PHASE 1/2 STUDY TO EVALUATE PALBOCICLIB (IBRANCE®) IN COMBINATION WITH IRINOTECAN AND TEMOZOLOMIDE OR IN COMBINATION WITH TOPOTECAN AND CYCLOPHOSPHAMIDE IN PEDIATRIC PATIENTS WITH RECURRENT OR REFRACTORY SOLID TUMORS
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Ewing Sarcoma
Solid Tumors
Rhabdoid Tumor
Rhabdomyosarcoma
Neuroblastoma
Medulloblastoma
Diffuse Intrinsic Pontine Glioma
Keywords: Ewing Sarcoma
EWS
Neuroblastoma
Recurrent Neuroblastoma
Solid Tumor
Recurrent Solid Tumors
Refractory Solid Tumors
Bone Cancer
Bone Tumor
Bone Sarcoma
Soft Tissue Cancer
Soft Tissue Sarcoma
Recurrent Ewing Sarcoma
Refractory Ewing Sarcoma
Relapsed Ewing Sarcoma
Pediatric Cancer
Childhood Cancer
Ewing Sarcoma Treatment
Palbociclib
CDK4/6 Inhibitor
Irinotecan
Temozolomide
Topotecan
Cyclophosphamide
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
Collaborators: name: Children's Oncology Group
First posted: 2018-10-17
Enrollment: 128
Sex: ALL
Minimum age (years): 2
Maximum age (years): 20
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Phase 1 portion: The palbociclib plus irinotecan and temozolomide combination part of the study will comprise of a dose escalation cohort (following a rolling 6 design), a dose expansion cohort.

The palbociclib plus topotecan and cyclophosphamide will comprise of a dose determination cohort(following a modified rolling 6 design), a dose expansion cohort, and Neuroblastoma tumor -specific cohort.

Phase 2 open-label, randomized portion of the study will randomize patients in a 2:1 ratio to receive either palbociclib in combination with irinotecan and temozolomide (Arm A) or irinotecan and temozolomide chemotherapy alone (Arm B). Randomization will be stratified using block randomization by type and time of current disease recurrence (primary refractory or 1st recurrence \< 2 years versus 1st recurrence ≥ 2 years or 2nd or greater recurrence).
Primary purpose: TREATMENT

Brief summary: A study to learn about safety and find out maximum tolerable dose of palbociclib given in combination with chemotherapy (temozolomide with irinotecan or topotecan with cyclophosphamide) in children, adolescents and young adults with recurrent or refractory solid tumors (phase 1). Neuroblastoma tumor specific cohort to further evaluate antitumor activity of palbociclib in combination with topotecan and cyclophosphamide in children, adolescents, and young adults with recurrent or refractory neuroblastoma. Phase 2 to learn about the efficacy of palbociclib in combination with irinotecan and temozolomide when compared with irinotecan and temozolomide alone in the treatment of children, adolescents, and young adults with recurrent or refractory Ewing sarcoma (EWS).


Eligibility criteria: Inclusion:

1. Histologically confirmed relapsed or refractory solid tumor as follows:

   * For dose escalation and dose determination parts: Histologically confirmed relapsed or refractory solid tumor (including CNS tumors but not lymphomas). Patients with Diffuse Intrinsic Pontine Glioma do not require histological only radiographic confirmed relapse to enroll.
   * For dose expansion and tumor specific cohorts: Histologically confirmed relapsed or refractory solid tumor including but not limited to EWS, rhabdoid tumor, rhabdomyosarcoma, neuroblastoma, and medulloblastoma. Patients with Diffuse Intrinsic Pontine Glioma do not require histological only radiographic confirmed relapse to enroll. EWS is not eligible for TOPO and CTX tumor-specific cohorts.
   * For randomized Phase 2 part: Histologically confirmed Ewing sarcoma at diagnosis or at relapse, with presence of EWSR1-ETS or FUS-ETS rearrangement. Histopathology confirmation of both EWSR1-ETS or FUS-ETS rearrangement partners is required OR availability of formalin fixed paraffin embedded (FFPE) tumor tissue sample for central testing. Patient must have relapsed or have refractory disease and at least evaluable disease in at least one site other than bone marrow that can be followed by imaging.
2. Age ≥2 and \<21 years at the time of study entry.
3. Lansky performance status ≥50% for patients ≤16 years of age, or Eastern Cooperative Oncology Group (ECOG) 0, 1 or 2 for patients \>16 years of age.
4. Adequate bone marrow function.

   * Absolute neutrophil count ≥1000/mm3;
   * Platelet count ≥75,000/mm3 (transfusion independent, no platelet transfusion in past 7 days prior study entry);
   * Hemoglobin ≥8.5 g/dL (transfusion allowed).
5. Adequate renal function: Serum creatinine level based on age/gender must within protocol specified limits.
6. Adequate liver function, including:

   * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)

     ≤2.5 × upper limit of normal (ULN) or ≤5 × ULN for age, if attributable to disease involvement of the liver;
   * Total bilirubin ≤1.5 × ULN for age, unless the patient has documented Gilbert's syndrome.Patients with documented Gilbert's syndrome are eligible if direct bilirubin is within normal ranges (≤ULN).
7. Patients enrolled to Phase 1 portion of the study and tumor specific cohorts must have measurable disease as defined by RECIST version 1.1 or modified RANO criteria for CNS disease or at least evaluable disease by INRC for neuroblastoma.

   The eligible patients with neuroblastoma must have at least one of the following at the time of study entry:
   * Measurable tumor by CT or MRI that is avid on MIBG scan or demonstrates increased FDG uptake on PET scan;
   * Avid lesion on MIBG scan with positive uptake at a minimum of one site;
   * For disease that is not avid by MIBG-scan, at least one lesion that demonstrates increased FDG uptake on PET scan AND viable neuroblastoma confirmed by current or prior biopsy;
   * bone marrow involvement with more than 5% neuroblastoma cells in at least one sample from bilateral bone marrow biopsies;
   * In non MIBG-avid refractory soft tissue disease that does not demonstrate increased FDG uptake; lesion biopsy is required to document the presence of viable neuroblastoma, unless patient has a new soft tissue lesion (radiographic evidence of disease progression).

   Patients with EWS enrolled to Phase 2 portion of the study are eligible with evaluable disease (eg, bone only disease with no soft tissue component).
8. Recovered to CTCAE Grade ≤1, or to baseline, from any non-hematological acute toxicities of prior surgery, chemotherapy, immunotherapy, radiotherapy, differentiation therapy or biologic therapy, with the exception of alopecia.
9. Serum/urine pregnancy test (for all girls ≥8 years of age) negative at screening and at the baseline visit.

Exclusion:

1. Phase 1 and tumor specific cohorts: For palbociclib with IRN and TMZ combination, prior treatment with a CDK4/6 inhibitor or progression while on treatment with an IRN-containing regimen that includes TMZ. Patients who have received the combination of IRN and TMZ and did not progress while on these medications are eligible. For patients enrolling in the palbociclib with TOPO and CTX combination, prior treatment with a CDK4/6 inhibitor or progression while on treatment with a TOPO-containing regimen that includes CTX. Patients who have received the combination of TOPO and CTX and did not progress while on these medications are eligible. Phase 2 portion: prior treatment with a CDK4/6 inhibitor or progression while on treatment with an IRN-containing or TMZ-containing regimen. Patients who have received IRN and/or TMZ and did not progress while on these medications are eligible.
2. Prior intolerability to IRN and/or TMZ plus/minus palbociclib with IRN and TMZ combination and prior intolerability to TOPO and/or CTX for TOPO and CTX combination. For patients enrolled in the UK, any contraindication for IRN and/or TMZ treatment, as per the local SmPC.
3. Use of strong cytochrome P450 (CYP) 3A inhibitors or inducers within 12 days of study entry. Patients who are receiving strong uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1) inhibitors within 12 days of Cycle 1 Day 1 (C1D1) are not eligible for the palbociclib with IRN and TMZ combination. Patients who are receiving strong UGT1A1 inhibitors within 12 days of C1D1 are eligible for the palbociclib with TOPO and CTX combination (See Section 5.7.1 for list of products.)
4. Systemic anti cancer therapy within 2 weeks prior to study entry and 6 weeks for nitrosoureas.
5. Prior irradiation to \>50% of the bone marrow (see Appendix 9).
6. Participation in other studies involving investigational drug(s) within 2 weeks or 5 half lives, whichever is longer, prior to study entry.
7. Major surgery within 4 weeks prior to study entry. Surgical biopsies or central line placement are not considered major surgeries.
8. For IRN and TMZ with/without palbociclib combinations: known or suspected hypersensitivity to palbociclib, dacarbazine, IRN and/or TMZ. For combination of palbociclib with TOPO and CTX: known or suspected hypersensitivity to palbociclib, TOPO and/or CTX.
9. Patients with known symptomatic brain tumors or brain metastases and require steroids, unless they have been on a stable or on a decreasing steroid dose for \>14 days.
10. Patients with previously diagnosed brain metastases are eligible if they have completed their prior treatment and have recovered from the acute effects of radiation therapy or surgery prior to study entry for these metastases for at least 14 days post radiation and 4 weeks post-surgery and are neurologically stable.
11. Hereditary bone marrow failure disorder.
12. QTc \>470 msec.
13. History of clinically significant or uncontrolled cardiac disease, including:

    * History of or active congestive heart failure; if patient had congestive heart failure resolve and \>1 year from resolution, patient will be considered eligible;
    * Clinically significant ventricular arrhythmia (such as ventricular tachycardia, ventricular fibrillation or Torsades de Pointes);
    * Diagnosed or suspected congenital or acquired prolonged QT syndrome;
    * Need for medications known to prolong the QT interval;
    * Uncorrected hypomagnesemia or hypokalemia because of potential effects on the QT interval;
    * Left ventricular ejection fraction \<50% or shortening fraction \<28%.
14. Recent or ongoing clinically significant gastrointestinal disorder that may interfere with absorption of orally administered drugs (eg, gastrectomy).
15. Evidence of serious active or uncontrolled bacterial, fungal or viral infection or known history of hepatitis B virus, hepatitis C virus, or human immunodeficiency virus infection or acquired immunodeficiency syndrome-related illness. Screening for viral hepatitis and HIV is under discretion of investigator unless required by local regulation.
16. Severe acute or chronic medical or laboratory test abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results, and in the judgment of the Investigator, would make the patient inappropriate for entry into this study.
17. Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or patients who are Pfizer employees, including their family members, directly involved in the conduct of the study.
18. Fertile male patients or female patients of childbearing potential who are unwilling or unable to follow contraceptive requirements.
19. Pregnant or breastfeeding women.

Primary outcomes:
measure: Phase 2 open-label, randomized: Event-free survival (EFS) based on Investigator assessment.
timeFrame: Baseline to Month 24.
measure: Phase 1: First Cycle Dose-Limiting Toxicities (DLT)
timeFrame: First cycle (cycle length is approximately 21 days)
measure: Phase 1: Dose Expansion Parts: Frequency of adverse events
timeFrame: At least 28 days after last dose
measure: Phase 1: Dose Expansion Parts: Percentage of Participants With Complete Response or Partial Response
timeFrame: Through the end of treatment (up to at least 28 days after last dose)
Secondary outcomes:
measure: Phase 1 and Phase 2: Frequency of adverse events
timeFrame: At least 28 days after last dose
measure: Phase 1 and Phase 2: Percentage of participants with laboratory abnormalities
timeFrame: At least 28 days after last dose
measure: Phase 1 and Phase 2: Number of Participants With Clinically Significant Treatment-emergent Electrocardiogram (ECG) Findings
timeFrame: At least 28 days after last dose
measure: Phase 1 and Phase 2: Number of Participants With Clinically Significant Change From Baseline in Vital Signs
timeFrame: At least 28 days after last dose
measure: Phase 2 open-label, randomized: Event-free survival (EFS) assessed by an independent review committee.
timeFrame: Baseline to Month 24.
measure: Phase 1 and Phase 2: Percentage of Participants With Complete Response or Partial Response
timeFrame: Through the end of treatment (up to at least 28 days after last dose)
measure: Phase 1 and Phase 2: Duration of response (DoR) for Participants Who Achieved Complete Response or Partial Response
timeFrame: Up to 2 years
measure: Phase 1 and Phase 2: Progression Free Survival (PFS)
timeFrame: Up to 2 years
measure: Phase 1 and Phase 2: Overall Survival (OS)
timeFrame: Up to 2 years
measure: Phase 2 : comparison of PET-CT response assessment to objective response on CT/MRI.
timeFrame: up to completion of Cycle 4 ( 12 weeks of therapy)
measure: Phase 2: the impact of the combination of palbociclib with TMZ and IRN treatment on the quality of life (QoL) of patients with refractory or recurrent EWS.
timeFrame: Up to Cycle 5 (completion of 12 weeks of treatment)
measure: Phase 1 and Phase 2:Palbociclib Pharmacokinetics, Maximum observed plasma concentration during a dosing interval at steady state (Css, max)
timeFrame: PK sampling at time points during Cycle 1 (day 2, 5, 6, 14) and Cycle 2 (day 5 and 14). Each cycle is 21 days.
measure: Phase 1 and Phase 2: Palbociclib Pharmacokinetics, Maximum plasma concentration time (Tmax)
timeFrame: PK sampling at time points during Cycle 1 (day 2, 5, 6, 14) and Cycle 2 (day 5 and 14). Each cycle is 21 days.
measure: Phase 1 and Phase 2: Palbociclib Pharmacokinetics, Area under the concentration-time curve during a dosing interval at steady state (AUCss,t)
timeFrame: PK sampling at time points during Cycle 1 (day 2,5, 6,14) and Cycle 2 (day 5 and 14). Each cycle is 21 days.
measure: Phase 1 and Phase 2: Palbociclib Pharmacokinetics, Measured concentration at the end of a dosing interval at steady state (taken directly before next administration) (Css,trough)
timeFrame: PK sampling at time points during Cycle 1 (day 2, 5, 6, 14) and Cycle 2 (day 5 and 14). Each cycle is 21 days.
measure: Phase 1 and Phase 2: Palbociclib Pharmacokinetics, Oral plasma clearance (CL/F)
timeFrame: PK sampling at time points during Cycle 1 (day 2, 5, 6, 14) and Cycle 2 (day 5 and 14). Each cycle is 21 days.
measure: Phase 1 and Phase 2: Temozolomide Pharmacokinetics, Maximum observed plasma concentration during a dosing interval at steady state (Css, max)
timeFrame: PK sampling at time points during Cycle 1 (day 5) and Cycle 2 (day 5). Each cycle is 21 days.
measure: Phase 1 and Phase 2: Temozolomide Pharmacokinetics, Maximum plasma concentration time (Tmax)
timeFrame: PK sampling at time points during Cycle 1 (day 5) and Cycle 2 (day 5). Each cycle is 21 days.
measure: Phase 1 and Phase 2: Temozolomide Pharmacokinetics, Area under the concentration-time curve during a dosing interval at steady state (AUCss,t)
timeFrame: PK sampling at time points during Cycle 1 (day 5) and Cycle 2 (day 5). Each cycle is 21 days.
measure: Phase 1 and Phase 2: Temozolomide Pharmacokinetics, Measured concentration at the end of a dosing interval at steady state (taken directly before next administration) (Css,trough)
timeFrame: PK sampling at time points during Cycle 1 (day 5) and Cycle 2 (day 5). Each cycle is 21 days.
measure: Phase 1 and Phase 2: Temozolomide Pharmacokinetics, Oral plasma clearance (CL/F)
timeFrame: PK sampling at time points during Cycle 1 (day 5) and Cycle 2 (day 5). Each cycle is 21 days.
measure: Phase 1 and Phase 2: Irinotecan (and active metabolites) Pharmacokinetics, Maximum observed plasma concentration during a dosing interval at steady state (Css, max)
timeFrame: PK sampling at time points during Cycle 1 (day 2, 5 and 6) and Cycle 2 (day 5). Each cycle is 21 days.
measure: Phase 1 and Phase 2: Irinotecan (and active metabolites) Pharmacokinetics, Maximum plasma concentration time (Tmax)
timeFrame: PK sampling at time points during Cycle 1 (day 2, 5 and 6) and Cycle 2 (day 5). Each cycle is 21 days.
measure: Phase 1 and Phase 2: Irinotecan (and active metabolites) Pharmacokinetics, Area under the concentration-time curve during a dosing interval at steady state (AUCss,t)
timeFrame: PK sampling at time points during Cycle 1 (day 2, 5 and 6) and Cycle 2 (day 5). Each cycle is 21 days.
measure: Phase 1 and Phase 2: Irinotecan (and active metabolites), Measured concentration at the end of a dosing interval at steady state (taken directly before next administration) (Css,trough)
timeFrame: PK sampling at time points during Cycle 1 (day 2, 5 and 6) and Cycle 2 (day 5). Each cycle is 21 days.
measure: Phase 1 and Phase 2: Irinotecan (and active metabolites) Pharmacokinetics, Oral plasma clearance (CL/F)
timeFrame: PK sampling at time points during Cycle 1 (day 2, 5 and 6) and Cycle 2 (day 5). Each cycle is 21 days.
measure: Phase 1: Topotecan (and active metabolites) Pharmacokinetics, Oral plasma clearance (CL/F)
timeFrame: PK sampling at time points during Cycle 1 (day 2, 5 and 6) and Cycle 2 (day 5). Each cycle is 21 days.
measure: Phase 1: Topotecan (and active metabolites), Measured concentration at the end of a dosing interval at steady state (taken directly before next administration) (Css,trough)
timeFrame: PK sampling at time points during Cycle 1 (day 2, 5 and 6) and Cycle 2 (day 5). Each cycle is 21 days.
measure: Phase 1: Topotecan (and active metabolites) Pharmacokinetics, Area under the concentration-time curve during a dosing interval at steady state (AUCss,t)
timeFrame: PK sampling at time points during Cycle 1 (day 2, 5 and 6) and Cycle 2 (day 5). Each cycle is 21 days.
measure: Phase 1: Topotecan (and active metabolites) Pharmacokinetics, Maximum plasma concentration time (Tmax)
timeFrame: PK sampling at time points during Cycle 1 (day 2, 5 and 6) and Cycle 2 (day 5). Each cycle is 21 days.
measure: Phase 1: Topotecan (and active metabolites) Pharmacokinetics, Maximum observed plasma concentration during a dosing interval at steady state (Css, max)
timeFrame: PK sampling at time points during Cycle 1 (day 2, 5 and 6) and Cycle 2 (day 5). Each cycle is 21 days.
measure: Phase 1: Cyclophosphamide Pharmacokinetics, Oral plasma clearance (CL/F)
timeFrame: PK sampling at time points during Cycle 1 (day 2, 5 and 6) and Cycle 2 (day 5). Each cycle is 21 days.
measure: Phase 1: Cyclophosphamide Pharmacokinetics, Maximum observed plasma concentration during a dosing interval at steady state (Css, max)
timeFrame: PK sampling at time points during Cycle 1 (day 2, 5 and 6) and Cycle 2 (day 5). Each cycle is 21 days.
measure: Phase 1: Cyclophosphamide Pharmacokinetics, Maximum plasma concentration time (Tmax)
timeFrame: PK sampling at time points during Cycle 1 (day 2, 5 and 6) and Cycle 2 (day 5). Each cycle is 21 days.
measure: Phase 1: Cyclophosphamide Pharmacokinetics, Area under the concentration-time curve during a dosing interval at steady state (AUCss,t)
timeFrame: PK sampling at time points during Cycle 1 (day 2, 5 and 6) and Cycle 2 (day 5). Each cycle is 21 days.
measure: Phase 1: Cyclophosphamide Pharmacokinetics, Measured concentration at the end of a dosing interval at steady state (taken directly before next administration) (Css,trough)
timeFrame: PK sampling at time points during Cycle 1 (day 2, 5 and 6) and Cycle 2 (day 5). Each cycle is 21 days.
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham/Children's of Alabama
state: Alabama
city: Phoenix
country: United States
facility: Phoenix Children's Hospital
state: Arizona
city: Long Beach
country: United States
facility: MemorialCare Health System - Long Beach Medical Center
state: California
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Oakland
country: United States
facility: Children's Hospital and Research Center at Oakland
state: California
city: Orange
country: United States
facility: Children's Hospital of Orange County
state: California
city: Palo Alto
country: United States
facility: Lucile Packard Children's Hospital
state: California
city: San Francisco
country: United States
facility: UCSF Medical Center
state: California
city: San Francisco
country: United States
facility: University of California San Francisco,
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Washington
country: United States
facility: Children's National Hospital
state: District of Columbia
city: Gainesville
country: United States
facility: UF Health Shands Hospital
state: Florida
city: Gainesville
country: United States
facility: University of Florida College of Medicine
state: Florida
city: Saint Petersburg
country: United States
facility: Johns Hopkins All Children's Hospital
state: Florida
city: Saint Petersburg
country: United States
facility: Johns Hopkins All Children's Outpatient Care Center
state: Florida
city: Tampa
country: United States
facility: Johns Hopkins All Children's Hospital
state: Florida
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta at Egleston
state: Georgia
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta at Scottish Rite
state: Georgia
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta, Medical Office Building
state: Georgia
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Louisville
country: United States
facility: Norton Children's Hospital
state: Kentucky
city: Louisville
country: United States
facility: Novak Center for Children's Health
state: Kentucky
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Ann Arbor
country: United States
facility: University of Michigan Health System
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota Masonic Children's Hospital
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota Medical Center, Fairview
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota/Masonic Cancer Center
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Kansas City
country: United States
facility: Children's Mercy Hospital
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New Brunswick
country: United States
facility: Robert Wood Johnson University Hospital
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Buffalo
country: United States
facility: John R. Oishei Childrens Hospital
state: New York
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New Hyde Park
country: United States
facility: Cohen Children's Medical Center
state: New York
city: New York
country: United States
facility: Morgan Stanley Children's Hospital of New York-Presbyetrian Hospital
state: New York
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Liberty Township
country: United States
facility: Cincinnati Children's Liberty Campus
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Hershey
country: United States
facility: Penn State Children's Hospital and Penn State Health Milton S. Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Buerger Center for Advanced Pediatric Care
state: Pennsylvania
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Children's Hospital of Pittsburgh
state: Pennsylvania
city: Austin
country: United States
facility: Children's Blood and Cancer Center
state: Texas
city: Austin
country: United States
facility: Dell Children's Medical Center
state: Texas
city: Dallas
country: United States
facility: Children's Medical Center Dallas
state: Texas
city: Fort Worth
country: United States
facility: Cook Children's Medical Center
state: Texas
city: Grapevine
country: United States
facility: Cook Children's H/O Infusion Center
state: Texas
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
city: Plano
country: United States
facility: Children's Medical Center Plano
state: Texas
city: Salt Lake City
country: United States
facility: Intermountain - Primary Children's Hospital
state: Utah
city: Salt Lake City
country: United States
facility: Primary Children's Hospital Outpatient Services
state: Utah
city: Norfolk
country: United States
facility: Children's Hospital of The King's Daughters
state: Virginia
city: Richmond
country: United States
facility: Children's Hospital of Richmond at VCU
state: Virginia
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Milwaukee
country: United States
facility: Children's Wisconsin
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Curitiba
country: Brazil
facility: Hospital Pequeno Principe / A ssociacao Hospitalar de Protecao a Infancia
state: Paraná
city: Curitiba
country: Brazil
facility: Hospital Pequeno Príncipe
state: Paraná
city: Porto Alegre
country: Brazil
facility: Hospital de Clinicas de Porto Alegre
state: RIO Grande DO SUL
city: Porto Alegre
country: Brazil
facility: Hospital de Clinicas de Porto Alegre
state: RIO Grande DO SUL
city: Barretos
country: Brazil
facility: Fundação Pio XII - Hospital de Câncer de Barretos
state: SÃO Paulo
city: Rio de Janeiro
country: Brazil
facility: Instituto Nacional de Câncer - INCA
city: São Paulo
country: Brazil
facility: Hospital Santa Marcelina
city: Calgary
country: Canada
facility: Alberta Children's Hospital
state: Alberta
city: Edmonton
country: Canada
facility: Stollery Children's Hospital
state: Alberta
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
city: Montreal
country: Canada
facility: CHU Sainte-Justine
state: Quebec
city: Brno
country: Czechia
facility: Detska nemocnice FN Brno
state: Brno-město
city: Praha
country: Czechia
facility: Fakultni nemocnice v Motole
state: Praha 5
city: Bordeaux
country: France
facility: Institut Bergonié - Centre Régional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest
state: Aquitaine
city: Lyon
country: France
facility: Centre Leon Berard
state: Rhône-alpes
city: Lyon
country: France
facility: Centre Leon Berard
state: Rhône-alpes
city: Villejuif
country: France
facility: Gustave Roussy
state: Val-de-marne
city: Marseille
country: France
facility: Assistance Publique Hôpitaux de Marseille - Hôpital de la Timone
city: Essen
country: Germany
facility: Universitätsklinikum Essen
state: Nordrhein-westfalen
city: New Delhi
country: India
facility: All India Institute of Medical Sciences
state: Delhi
city: New Delhi
country: India
facility: Rajiv Gandhi Cancer Institute And Research Centre
state: Delhi
city: Gurugram
country: India
facility: Artemis hospital
state: Haryana
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center
state: Kyǒnggi-do
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
state: Seoul-teukbyeolsi [seoul]
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
state: Seoul-teukbyeolsi [seoul]
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
state: Seoul-teukbyeolsi [seoul]
city: Warsaw
country: Poland
facility: Instytut Matki i Dziecka
state: Mazowieckie
city: Banska Bystrica
country: Slovakia
facility: Detska fakultna nemocnica s poliklinikou Banska Bystrica
city: Bratislava
country: Slovakia
facility: Narodny ustav detskych chorob
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
state: Barcelona [barcelona]
city: Madrid
country: Spain
facility: Hospital Infantil Universitario Niño Jesús
state: Madrid, Comunidad DE
city: Gothenburg
country: Sweden
facility: Sahlgrenska Universitetssjukhuset Östra
state: Västra Götalands LÄN [se-14]
city: İzmir
country: Turkey
facility: Ege Universitesi Hastanesi
state: İ̇zmir
city: Ankara
country: Turkey
facility: Hacettepe Universite Hastaneleri
city: Newcastle upon Tyne
country: United Kingdom
facility: Royal Victoria Infirmary
state: England
city: Glasgow
country: United Kingdom
facility: Royal Hospital for Children
state: Scotland
city: Leeds
country: United Kingdom
facility: Leeds General Infirmary
city: London
country: United Kingdom
facility: University College London Hospital, NHS Foundation Trust
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: