Clinical trial NCT05828069: A Study With Tovorafenib (DAY101) as a Treatment Option for Progressive, Relapsed, or Refractory Langerhans Cell Histiocytosis
Official title: Phase 2 Study of Tovorafenib (DAY101) in Relapsed and Refractory Langerhans Cell Histiocytosis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Recurrent Langerhans Cell Histiocytosis
Refractory Langerhans Cell Histiocytosis
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2023-04-25
Enrollment: 48
Sex: ALL
Minimum age (years): 180
Maximum age (years): 22
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This phase II trial tests the safety, side effects, best dose and activity of tovorafenib (DAY101) in treating patients with Langerhans cell histiocytosis that is growing, spreading, or getting worse (progressive), has come back (relapsed) after previous treatment, or does not respond to therapy (refractory). Langerhans cell histiocytosis is a type of disease that occurs when the body makes too many immature Langerhans cells (a type of white blood cell). When these cells build up, they can form tumors in certain tissues and organs including bones, skin, lungs and pituitary gland and can damage them. This tumor is more common in children and young adults. DAY101 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Using DAY101 may be effective in treating patients with relapsed or refractory Langerhans cell histiocytosis.

Detailed description: PRIMARY OBJECTIVE:

I. To determine overall response rate (ORR) for children and young adults with relapsed or refractory BRAFV600E positive (cohort 1) and BRAFV600E negative (cohort 2) Langerhans cell histiocytosis (LCH) treated with tovorafenib (DAY101) after 2 cycles and must be maintained 4 weeks later.

SECONDARY OBJECTIVES:

I. To determine nature and severity of adverse events in patients treated with tovorafenib (DAY101) for relapsed or refractory LCH.

II. To describe event-free survival (EFS) at 1 year in children and young adults with relapsed and refractory LCH treated with tovorafenib (DAY 101) for up to 1 year.

III. To determine durability of response in children and young adults with relapsed or refractory LCH treated with tovorafenib (DAY101) following cessation of therapy in patients with complete response (CR) at 1 year.

IV. To describe progression-free (and relapse-free) survival (PFS) and overall survival (OS) in children and young adults with relapsed or refractory LCH treated with tovorafenib (DAY101) for up to 1 year.

EXPLORATORY OBJECTIVES:

I. To determine potential role of pathogenic tumor mutation in response to tovorafenib (DAY101), and to evaluate changes in bone marrow and peripheral blood cell populations carrying pathogenic mutations in response to tovorafenib (DAY101) therapy.

Ia. To define somatic mutations in LCH lesion biopsies; Ib. To determine impact of tovorafenib (DAY101) on bone marrow and blood BRAFV600E+ mononuclear cells; Ic. To determine impact of tovorafenib (DAY101) on cerebral spinal fluid and disease response; Id. To determine the performance of standardized immunohistochemical analysis of LCH lesion biopsies.

II. To compare performance of LCH-specific response criteria to Response Evaluation Criteria in Solid Tumors (RECIST).

III. To describe the pharmacokinetics of tovorafenib (DAY101) when administered to pediatric and young adult patients with relapse or refractory LCH.

OUTLINE: This is a dose escalation study of tovorafenib followed by a phase II trial.

Patients receive tovorafenib orally (PO) once weekly (QW) on days 1, 8, 15, and 22 of each cycle. Cycles repeat every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo multi-gated acquisition (MUGA) or echocardiography (ECHO) scans, and fludeoxyglucose F-18 (FDG)-positron emission tomography (PET) or computed tomography (CT) throughout the trial, and collection of blood samples on study. Patients with suspicion of bone marrow and/or central nervous system involvement will also undergo bone marrow biopsy and aspiration and lumbar puncture on study and during follow up.

After completion of study treatment, patients are followed up at 28 days, months 3, 6, 9, and 12, and then at 2 years post cycle 12.

Eligibility criteria: Inclusion Criteria:

* 180 days- \< 22 years (at time of study enrollment)
* Patient must have a body surface area of ≥ 0.3 m\^2
* Patients with progressive, relapsed, or recurrent LCH with measurable disease at study entry

  * Patients must have had histologic verification of LCH (from either original diagnosis or relapse/progression) at the time of study entry (must be obtained within 28 days prior to enrollment and start of protocol therapy) (repeat if necessary)

    * Tissue confirmation of relapse is recommended but not required
    * Pathology report must be submitted for central confirmation of diagnosis within 7 days of enrollment.
    * Formalin-fixed paraffin-embedded (FFPE) blocks or unstained slides (initial diagnosis and/or subsequent biopsies) will be required for retrospective central confirmation of diagnosis and molecular studies
    * Patients with mixed histiocytic disorders (e.g. LCH with juvenile xanthogranuloma) may be included
  * Patients must have measurable disease, documented by radiographic imaging (LCH- specific response criteria (must be obtained within 28 days prior to enrollment and start of protocol therapy) (repeat if necessary).
  * Patients must have progressive or refractory disease or experience relapse after at least one previous systemic treatment strategy
  * Pathogenic somatic mutation detected in genes encoding tyrosine kinase receptors (CSFR1, ERBB3 or ALK), RAS or RAF (may be from original or subsequent biopsy or peripheral blood/bone marrow aspirate). Clinical mutation reports may include quantitative polymerase chain reaction (PCR) (e.g. BRAFV600E) and/or Sanger or next generation sequencing. Immunohistochemistry (e.g. VE1 antibody for BRAFV600E) alone is not sufficient
* Participant must be able to take an enteral dose and formulation of medication. Study medication is only available as an oral suspension or tablet, which may be taken by mouth or other enteral route such as nasogastric, jejunostomy, or gastric tube
* Karnofsky \>= 50% for patients \> 16 years of age and Lansky \>= 50% for patients =\< 16 years of age
* Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients \> 16 years of age and Lansky for patients =\< 16 years of age
* Myelosuppressive chemotherapy: Patients must not have received within 14 days of entry onto this study
* Investigational agent or any other anticancer therapy not defined above: Patients must not have received any investigational agent or any other anticancer therapy (including MAPK pathway inhibitor) for at least 14 days prior to planned start of tovorafenib (DAY101)
* Radiation therapy (RT): Patient must not have received RT within 2 weeks after the last dose fraction of RT
* Patients must have fully recovered from any prior surgery
* Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, targeted inhibitor, and/or radiotherapy with toxicities reduced to grade 1 or less (Common Terminology Criteria for Adverse Events \[CTCAE\] version 5.0)
* Steroids: =\< 0.5 mg/kg/day of prednisone equivalent (maximum 20 mg/day) averaged during the month prior to study enrollment is permissible
* Strong inducers or inhibitors of CYP2C8 are prohibited for 14 days before the first dose of tovorafenib (DAY101) and from planned administration for the duration of study participation
* Medications that are breast cancer resistant protein (BCRP) substrates that have a narrow therapeutic index are prohibited for 14 days before the first dose of tovorafenib (DAY101) and for the duration of study participation
* Peripheral absolute neutrophil count (ANC) \>= 750/uL unless secondary to bone marrow involvement, in such cases bone marrow involvement must be documented (must be performed within 7 days prior to enrollment, must be repeated prior to the start of protocol therapy if \> 7 days have elapsed from their most recent prior assessment)
* Platelet count \>= 75,000/uL (unsupported/without transfusion within the past 7 days) (must be performed within 7 days prior to enrollment, must be repeated prior to the start of protocol therapy if \> 7 days have elapsed from their most recent prior assessment)
* Patients with marrow disease must have platelet count of \>= 75,000/uL (transfusion support allowed) and must not be refractory to platelet transfusions. Bone marrow involvement must be documented
* Hemoglobin \>= 8 g/dL (unsupported/without transfusion within the past 7 days). Patients with marrow disease must have hemoglobin \>= 8 g/dL (transfusion support allowed). Bone marrow involvement must be documented
* Hematopoietic growth factors: At least 14 days after the last dose of a long-acting growth factor (e.g., Neulasta \[registered trademark\]) or 7 days for short-acting growth factor
* A serum creatinine based on age/gender as follows (must be performed within 7 days prior to enrollment, must be repeated prior to the start of protocol therapy if \> 7 days have elapsed from their most recent prior assessment)

  * Age: 6 months to \< 1 year; Maximum Serum Creatinine (mg/dL):= 0.5 mg/dl (male and female)
  * Age: 1 to \< 2 years; Maximum Serum Creatinine (mg/dL): = 0.6 mg/dl (male and female)
  * Age: 2 to \< 6 years; Maximum Serum Creatinine (mg/dL): = 0.8 mg/dl (male and female)
  * Age: 6 to \< 10 years; Maximum Serum Creatinine (mg/dL): = 1.0 mg/dl (male and female)
  * Age: 10 to \< 13 years; Maximum Serum Creatinine (mg/dL): = 1.2 mg/dl (male and female)
  * 13 to \< 16 years; Maximum Serum Creatinine (mg/dL): = 1.5 mg/dl (male) and 1.4 mg/dl (female)
  * Age: \>= 16 years; Maximum Serum Creatinine (mg/dL): = 1.7 mg/dl (male) and 1.4 mg/dl (female)
  * OR- a 24 hour urine creatinine clearance \>= 50 mL/min/1.73 m\^2
  * OR- a glomerular filtration rate (GFR) \>= 50 mL/min/1.73 m\^2. GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard)
  * Note: Estimated GFR (eGFR) from serum creatinine, cystatin C or other estimates are not acceptable for determining eligibility
* Bilirubin (sum of conjugated + unconjugated) =\< 1.5 x upper limit of normal (ULN) for age (must be performed within 7 days prior to enrollment, must be repeated prior to the start of protocol therapy if \> 7 days have elapsed from their most recent prior assessment)
* Alanine aminotransferase (ALT) =\< 3 x ULN for age (must be performed within 7 days prior to enrollment, must be repeated prior to the start of protocol therapy if \> 7 days have elapsed from their most recent prior assessment)
* Serum albumin \>= 2 g/dl must be performed within 7 days prior to enrollment, must be repeated prior to the start of protocol therapy if \> 7 days have elapsed from their most recent prior assessment)
* For patients with liver disease caused by their histiocytic disorder (as evaluated on radiographic imaging or biopsy): patients may be enrolled with abnormal bilirubin, aspartate aminotransferase (AST), ALT and albumin with documentation of histiocytic liver disease
* Fractional shortening (FS) of \>= 25% or ejection fraction of \>= 50%, as determined by echocardiography or multigated acquisition scan (MUGA) within 28 days prior to study enrollment. Depending on institutional standard, either FS or left ventricular ejection fraction (LVEF) is adequate for enrollment if only one value is measured; if both values are measured, then both values must meet criteria above (must be obtained within 28 days prior to enrollment and start of protocol therapy) (repeat if necessary)
* No evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry \> 94% if there is clinical indication for determination; unless it is due to underlying pulmonary LCH
* Central Nervous System Function Defined As:

  * Patients with seizure disorder may be enrolled if well controlled
  * Central nervous system (CNS) toxicity =\< Grade 2
* Human immunodeficiency virus (HIV) infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial unless antiretroviral therapy interacts with the metabolism of tovorafenib (DAY101) and cannot safely be changed to antivirals that do not interact with study medication

Exclusion Criteria:

* LCH arising along with other hematologic malignancy (e.g. mixed LCH with acute lymphoblastic leukemia) or any history of non-histiocytic malignancy
* Disease scenarios as below will be excluded

  * Skin-limited disease
  * Gastrointestinal (GI) tract involvement only (those that have disease that can be determined by endoscopic biopsies only)
  * LCH-associated neurodegeneration (LCH-ND) without parenchymal lesions or other systemic lesions
* Patients with activating mutations in MAP2K1 are not eligible for this study due to drug target specificity. Mutation status will be submitted to study team within 7 days of enrollment
* Refractory nausea and vomiting, malabsorption, or external biliary shunt that would preclude adequate absorption of tovorafenib (DAY101)
* Uncontrolled systemic bacterial, viral, or fungal infection
* Major surgical procedure or significant traumatic injury within 14 days prior to study enrollment, or anticipation of need for major surgical procedure during the course of the study. Placement of a vascular access device or minor surgery is permitted within fourteen (14) days of study enrollment (provided that the wound has healed)
* History of significant bowel resection that would preclude adequate absorption or other significant malabsorptive disease
* Ophthalmologic considerations: Patients with known significant ophthalmologic conditions or known risk factors for retinal vein occlusion (RVO) or central serous retinopathy (CSR) are not eligible
* History of solid organ or hematopoietic bone marrow transplantation
* Clinically significant active cardiovascular disease, or history of myocardial infarction, or deep vein thrombosis/pulmonary embolism within 6 months prior to enrollment, ongoing cardiomyopathy, or current prolonged QT interval \> 440 ms based on triplicate electrocardiogram (ECG) average
* History of Grade \>= 2 CNS hemorrhage or history of any CNS hemorrhage within 28 days of study entry
* History of any drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome or Stevens Johnsons syndrome (SJS) or who are allergic to tovorafenib (DAY101) or any of its components
* CTCAE version (V). 5.0 Grade 3 symptomatic creatinine kinase (CPK) elevation ( \> 5 x ULN)
* Female patients who are pregnant are ineligible. A pregnancy test is required for female patients of childbearing potential
* Lactating females who plan to breastfeed their infants are ineligible
* Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation are ineligible. Participants (male and female) who are sexually active must use two forms of an acceptable method of birth control (for men, one form must be a barrier method) from start of therapy through 180 days following last dose of tovorafenib (DAY101)

Primary outcomes:
measure: Frequency of dose limiting toxicity (DLT) (dose finding phase)
timeFrame: Up to 28 days
measure: Overall response rate (ORR) (phase II)
timeFrame: After 2 cycles of therapy (each cycle is 28 days)
Secondary outcomes:
measure: Event free survival rate (EFS)
timeFrame: At 1 and 2 years
measure: Progression free survival rate (PFS)
timeFrame: Up to 2 years
measure: Duration of response rate
timeFrame: After 12 months of therapy. From the scan confirming the complete response or partial response (whichever is recorded first), until the first occurrence of recurrent or progressive disease or death (event) or last known status on trial
measure: Overall survival rate (OS)
timeFrame: Up to 2 years
Other outcomes:
measure: Percent peripheral blood mononuclear cells (PBMC) with mutated allele
timeFrame: Up to 2 years
Locations:
city: Birmingham
country: United States
facility: Children's Hospital of Alabama
state: Alabama
city: Little Rock
country: United States
facility: Arkansas Children's Hospital
state: Arkansas
city: Downey
country: United States
facility: Kaiser Permanente Downey Medical Center
state: California
city: Loma Linda
country: United States
facility: Loma Linda University Medical Center
state: California
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Madera
country: United States
facility: Valley Children's Hospital
state: California
city: Oakland
country: United States
facility: UCSF Benioff Children's Hospital Oakland
state: California
city: Oakland
country: United States
facility: Kaiser Permanente-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 Stanford University
state: California
city: San Francisco
country: United States
facility: UCSF Medical Center-Mission Bay
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Denver
country: United States
facility: Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
state: Colorado
city: Hartford
country: United States
facility: Connecticut Children's Medical Center
state: Connecticut
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Wilmington
country: United States
facility: Alfred I duPont Hospital for Children
state: Delaware
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Fort Myers
country: United States
facility: Golisano Children's Hospital of Southwest Florida
state: Florida
city: Gainesville
country: United States
facility: University of Florida Health Science Center - Gainesville
state: Florida
city: Jacksonville
country: United States
facility: Nemours Children's Clinic-Jacksonville
state: Florida
city: Miami
country: United States
facility: Nicklaus Children's Hospital
state: Florida
city: Orlando
country: United States
facility: Arnold Palmer Hospital for Children
state: Florida
city: Orlando
country: United States
facility: Nemours Children's Hospital
state: Florida
city: Tampa
country: United States
facility: Saint Joseph's Hospital/Children's Hospital-Tampa
state: Florida
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta - Arthur M Blank Hospital
state: Georgia
city: Savannah
country: United States
facility: Memorial Health University Medical Center
state: Georgia
city: Chicago
country: United States
facility: Lurie Children's Hospital-Chicago
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Comprehensive Cancer Center
state: Illinois
city: Peoria
country: United States
facility: Saint Jude Midwest Affiliate
state: Illinois
city: Indianapolis
country: United States
facility: Riley Hospital for Children
state: Indiana
city: Des Moines
country: United States
facility: Blank Children's Hospital
state: Iowa
city: Iowa City
country: United States
facility: University of Iowa/Holden Comprehensive Cancer Center
state: Iowa
city: Lexington
country: United States
facility: University of Kentucky/Markey Cancer Center
state: Kentucky
city: New Orleans
country: United States
facility: Children's Hospital New Orleans
state: Louisiana
city: Baltimore
country: United States
facility: Sinai Hospital of Baltimore
state: Maryland
city: East Lansing
country: United States
facility: Michigan State University Clinical Center
state: Michigan
city: Grand Rapids
country: United States
facility: Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
state: Michigan
city: Minneapolis
country: United States
facility: Children's Hospitals and Clinics of Minnesota - Minneapolis
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota/Masonic Cancer Center
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Saint Louis
country: United States
facility: Cardinal Glennon Children's Medical Center
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Saint Louis
country: United States
facility: Mercy Hospital Saint Louis
state: Missouri
city: Omaha
country: United States
facility: Children's Hospital and Medical Center of Omaha
state: Nebraska
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Las Vegas
country: United States
facility: Alliance for Childhood Diseases/Cure 4 the Kids Foundation
state: Nevada
city: Las Vegas
country: United States
facility: Summerlin Hospital Medical Center
state: Nevada
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
state: New Jersey
city: Paterson
country: United States
facility: Saint Joseph's Regional Medical Center
state: New Jersey
city: Albany
country: United States
facility: Albany Medical Center
state: New York
city: Bronx
country: United States
facility: Montefiore Medical Center - Moses Campus
state: New York
city: Brooklyn
country: United States
facility: Maimonides Medical Center
state: New York
city: New Hyde Park
country: United States
facility: The Steven and Alexandra Cohen Children's Medical Center of New York
state: New York
city: New York
country: United States
facility: Laura and Isaac Perlmutter Cancer Center at NYU Langone
state: New York
city: New York
country: United States
facility: NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: New York
country: United States
facility: NYP/Weill Cornell Medical Center
state: New York
city: Valhalla
country: United States
facility: New York Medical College
state: New York
city: Asheville
country: United States
facility: Mission Hospital
state: North Carolina
city: Greenville
country: United States
facility: East Carolina University
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Cleveland
country: United States
facility: Rainbow Babies and Childrens Hospital
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Dayton
country: United States
facility: Dayton Children's Hospital
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 and Science University
state: Oregon
city: Danville
country: United States
facility: Geisinger Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Philadelphia
country: United States
facility: Saint Christopher's Hospital for Children
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
city: Columbia
country: United States
facility: Prisma Health Richland Hospital
state: South Carolina
city: Greenville
country: United States
facility: BI-LO Charities Children's Cancer Center
state: South Carolina
city: Knoxville
country: United States
facility: East Tennessee Childrens Hospital
state: Tennessee
city: Nashville
country: United States
facility: The Children's Hospital at TriStar Centennial
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University/Ingram Cancer Center
state: Tennessee
city: Austin
country: United States
facility: Dell Children's Medical Center of Central Texas
state: Texas
city: Dallas
country: United States
facility: UT Southwestern/Simmons Cancer Center-Dallas
state: Texas
city: El Paso
country: United States
facility: El Paso Children's Hospital
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
state: Texas
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: Children's Hospital of San Antonio
state: Texas
city: San Antonio
country: United States
facility: Methodist Children's Hospital of South Texas
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: Temple
country: United States
facility: Scott and White Memorial Hospital
state: Texas
city: Salt Lake City
country: United States
facility: Primary Children's Hospital
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia Cancer Center
state: Virginia
city: Norfolk
country: United States
facility: Children's Hospital of The King's Daughters
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University/Massey Cancer Center
state: Virginia
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Spokane
country: United States
facility: Providence Sacred Heart Medical Center and Children's Hospital
state: Washington
city: Charleston
country: United States
facility: West Virginia University Charleston Division
state: West Virginia
city: Randwick
country: Australia
facility: Sydney Children's Hospital
state: New South Wales
city: South Brisbane
country: Australia
facility: Queensland Children's Hospital
state: Queensland
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
city: Halifax
country: Canada
facility: IWK Health Centre
state: Nova Scotia
city: Hamilton
country: Canada
facility: McMaster Children's Hospital at Hamilton Health Sciences
state: Ontario
city: London
country: Canada
facility: Children's Hospital
state: Ontario
city: Toronto
country: Canada
facility: Hospital for Sick Children
state: Ontario
city: Montreal
country: Canada
facility: Centre Hospitalier Universitaire Sainte-Justine
state: Quebec
city: Sherbrooke
country: Canada
facility: Centre Hospitalier Universitaire de Sherbrooke-Fleurimont
state: Quebec
city: Quebec
country: Canada
facility: CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)
Study officials:
affiliation: Children's Oncology Group
name: Michelle L Hermiston
role: PRINCIPAL_INVESTIGATOR
References: