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
