Erdafitinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With FGFR Mutations (A Pediatric MATCH Treatment Trial)
Erdafitinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With FGFR Mutations (A Pediatric MATCH Treatment Trial)
This phase II Pediatric MATCH trial studies how well erdafitinib works in treating patients
 with solid tumors, non-Hodgkin lymphoma, or histiocytic disorders that have spread to other
 places in the body and have come back or do not respond to treatment with FGFR mutations.
 Erdafitinib may stop the growth of cancer cells by blocking some of the enzymes needed for
 cell growth.
PRIMARY OBJECTIVES:

 I. To determine the objective response rate (ORR; complete response + partial response) in
 pediatric patients treated with JNJ-42756493 (erdafitinib) with advanced solid tumors
 (including central nervous system [CNS] tumors), non-Hodgkin lymphomas or histiocytic
 disorders that harbor genetic alterations in the FGFR1/2/3/4 pathway.

 SECONDARY OBJECTIVES:

 I. To estimate the progression free survival in pediatric patients treated with JNJ-42756493
 (erdafitinib) with advanced solid tumors (including CNS tumors), non-Hodgkin lymphomas or
 histiocytic disorders that harbor genetic alterations in the FGFR1/2/3/4.

 II. To obtain information about the tolerability of JNJ-42756493 (erdafitinib) in children
 with relapsed or refractory cancer.

 III. To provide preliminary estimates of the pharmacokinetics of JNJ-42756493 (erdafitinib)
 in children with relapsed or refractory cancer.

 EXPLORATORY OBJECTIVES:

 I. To explore approaches to profiling changes in tumor genomics over time through evaluation
 of circulating tumor deoxyribonucleic acid (DNA).

 OUTLINE:

 Patients receive erdafitinib orally (PO) once daily (QD) on days 1-28. Cycles repeat every 28
 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

 After completion of study treatment, patients are followed up periodically.
Inclusion Criteria:

 -  Patient must have enrolled onto APEC1621SC and must have been given a treatment
 assignment to molecular analysis for therapy choice (MATCH) to APEC1621B based on the
 presence of an actionable mutation

 -  Patients must have a body surface area >= 0.53 m^2 at enrollment

 -  Patients must have radiographically measurable disease at the time of study
 enrollment; patients with neuroblastoma who do not have measurable disease but have
 metaiodobenzylguanidine (MIBG) positive (+) evaluable disease are eligible; measurable
 disease in patients with CNS involvement is defined as tumor that is measurable in two
 perpendicular diameters on magnetic resonance imaging (MRI) and visible on more than
 one slice

 -  Note: The following do not qualify as measurable disease:

 -  Malignant fluid collections (e.g., ascites, pleural effusions)

 -  Bone marrow infiltration except that detected by MIBG scan for neuroblastoma

 -  Lesions only detected by nuclear medicine studies (e.g., bone, gallium or
 positron emission tomography [PET] scans) except as noted for neuroblastoma

 -  Elevated tumor markers in plasma or cerebrospinal fluid (CSF)

 -  Previously radiated lesions that have not demonstrated clear progression
 post radiation

 -  Leptomeningeal lesions that do not meet the measurement requirements for
 Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

 -  Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients =< 16
 years of age; Note: neurologic deficits in patients with CNS tumors must have been
 stable for at least 7 days prior to study enrollment; patients who are unable to walk
 because of paralysis, but who are up in a wheelchair, will be considered ambulatory
 for the purpose of assessing the performance score

 -  Patients must have fully recovered from the acute toxic effects of all prior
 anti-cancer therapy and must meet the following minimum duration from prior
 anti-cancer directed therapy prior to enrollment; if after the required timeframe, the
 numerical eligibility criteria are met, e.g. blood count criteria, the patient is
 considered to have recovered adequately

 -  Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive;
 >= 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy (42
 days if prior nitrosourea)

 -  Anti-cancer agents not known to be myelosuppressive (e.g. not associated with
 reduced platelet or absolute neutrophil count [ANC] counts): >= 7 days after the
 last dose of agent

 -  Antibodies: >= 21 days must have elapsed from infusion of last dose of antibody,
 and toxicity related to prior antibody therapy must be recovered to grade =< 1

 -  Corticosteroids: if used to modify immune adverse events related to prior
 therapy, >= 14 days must have elapsed since last dose of corticosteroid

 -  Hematopoietic growth factors: >= 14 days after the last dose of a long-acting
 growth factor (e.g. pegfilgrastim) or 7 days for short-acting growth factor; for
 growth factors that have known adverse events occurring beyond 7 days after
 administration, this period must be extended beyond the time during which adverse
 events are known to occur; the duration of this interval must be discussed with
 the study chair and the study-assigned research coordinator

 -  Interleukins, interferons and cytokines (other than hematopoietic growth
 factors): >= 21 days after the completion of interleukins, interferon or
 cytokines (other than hematopoietic growth factors)

 -  Stem cell infusions (with or without total body irradiation [TBI]):

 -  Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem
 cell infusion including donor lymphocyte infusion (DLI) or boost infusion:
 >= 84 days after infusion and no evidence of graft versus host disease
 (GVHD)

 -  Autologous stem cell infusion including boost infusion: >= 42 days

 -  Cellular therapy: >= 42 days after the completion of any type of cellular therapy
 (e.g. modified T cells, natural killer [NK] cells, dendritic cells, etc.)

 -  X-ray therapy (XRT)/external beam irradiation including protons: >= 14 days after
 local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to >= 50% of
 the pelvis; >= 42 days if other substantial bone marrow (BM) radiation

 -  Note: radiation may not be delivered to "measurable disease" tumor site(s)
 being used to follow response to subprotocol treatment

 -  Radiopharmaceutical therapy (e.g., radiolabeled antibody, iobenguane I-131
 [131I-MIBG]): >= 42 days after systemically administered radiopharmaceutical
 therapy

 -  Patients must not have received prior exposure to JNJ-42756493 (erdafitinib) or
 another FGFR inhibitor such as (but not limited to) AZD4547, BGJ398, BAY1163877,
 LY2874455

 -  For patients with solid tumors without known bone marrow involvement:

 -  Peripheral absolute neutrophil count (ANC) >= 1000/mm^3

 -  Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving
 platelet transfusions for at least 7 days prior to enrollment)

 -  Hemoglobin >= 8.0 g/dL at baseline (may receive red blood cell [RBC]
 transfusions)

 -  Patients with known bone marrow metastatic disease will be eligible for study provided
 they meet the blood counts (may receive platelet or packed [p]RBC transfusions
 provided they are not known to be refractory to red cell or platelet transfusions);
 these patients will not be evaluable for hematologic toxicity

 -  Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70
 ml/min/1.73 m^2 or a serum creatinine based on age/gender as follows:

 -  Age: 1 to < 2 years; maximum serum creatinine (mg/dL): male 0.6; female 0.6

 -  Age: 2 to < 6 years; maximum serum creatinine (mg/dL): male 0.8; female 0.8

 -  Age: 6 to < 10 years; maximum serum creatinine (mg/dL): male 1; female 1

 -  Age: 10 to < 13 years; maximum serum creatinine (mg/dL): male 1.2; female 1.2

 -  Age: 13 to < 16 years; maximum serum creatinine (mg/dL): male 1.5; female 1.4

 -  Age: >= 16 years; maximum serum creatinine (mg/dL): male 1.7; female 1.4

 -  Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for
 age

 -  Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135
 U/L; (for the purpose of this study, the ULN for SGPT is 45 U/L)

 -  Serum albumin >= 2 g/dL

 -  Corrected QT (QTc) interval =< 480 milliseconds

 -  Pulse oximetry > 94% on room air if there is clinical indication for determination
 (e.g. dyspnea at rest)

 -  Patients must be able to swallow intact tablets

 -  All patients and/or their parents or legally authorized representatives must sign a
 written informed consent; assent, when appropriate, will be obtained according to
 institutional guidelines

 Exclusion Criteria:

 -  Pregnant or breast-feeding women will not be entered on this study due to risks of
 fetal and teratogenic adverse events as seen in animal studies; pregnancy tests must
 be obtained in girls who are post-menarchal; males or females of reproductive
 potential may not participate unless they have agreed to use an effective
 contraceptive method, while receiving study treatment and for 3 months after the last
 dose of JNJ-42756493 (erdafitinib); male subjects (with a partner of child-bearing
 potential) must use a condom with spermicide when sexually active and must not donate
 sperm from the first dose of study drug until 5 months after the last dose of study
 drug

 -  Concomitant medications

 -  Corticosteroids: patients receiving corticosteroids who have not been on a stable
 or decreasing dose of corticosteroid for at least 7 days prior to enrollment are
 not eligible; if used to modify immune adverse events related to prior therapy,
 >= 14 days must have elapsed since last dose of corticosteroid

 -  Investigational drugs: patients who are currently receiving another
 investigational drug are not eligible

 -  Anti-cancer agents: patients who are currently receiving other anti-cancer agents
 are not eligible

 -  Anti-GVHD agents post-transplant: patients who are receiving cyclosporine,
 tacrolimus or other agents to prevent graft-versus-host disease post bone marrow
 transplant are not eligible for this trial

 -  CYP3A4 agents: patients who are currently receiving drugs that are strong
 inducers or inhibitors of CYP3A4 are not eligible; Note: CYP3A4 inducing
 anti-epileptic drugs and dexamethasone for CNS tumors or metastases, on a stable
 dose, are allowed

 -  CYP2C9 agents: patients who are currently receiving drugs that are moderate to
 strong inducers or inhibitor of CYP2C9 are not eligible

 -  P-glycoprotein: patients who are currently receiving drugs that are potent
 inhibitors of p-glycoprotein are not eligible

 -  Patients who have an uncontrolled infection are not eligible

 -  Patients who have received a prior solid organ transplantation are not eligible

 -  Patients who in the opinion of the investigator may not be able to comply with the
 safety monitoring requirements of the study are not eligible

 -  A history of cardiovascular diseases: unstable angina, myocardial infarction, or known
 congestive heart failure class IIIV within the preceding 12 months; cerebrovascular
 accident or transient ischemic attack within the preceding 3 months, pulmonary
 embolism within the preceding 2 months

 -  A history of any of the following: sustained ventricular tachycardia, ventricular
 fibrillation, torsades de pointes, cardiac arrest, Mobitz II second degree heart block
 or third degree heart block; known presence of dilated, hypertrophic, or restrictive
 cardiomyopathy

 -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
 infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
 arrhythmia, or psychiatric illness/social situations that would limit compliance with
 study requirements

 -  Patients with known significant ophthalmologic conditions (uncontrolled glaucoma,
 history of retinal vein occlusion or retinal detachment, excluding patients with
 longstanding findings secondary to existing conditions) are not eligible