PRIMARY OBJECTIVES:
I. To utilize clinical and biological data to screen for eligibility to phase 2
pathway-targeting specific subprotocols of pathway-targeting agents in pediatric patients
with advanced solid tumors, non-Hodgkin lymphomas, and histiocytic disorders.
II. To determine the proportion of pediatric patients whose advanced tumors have pathway
alterations that can be targeted by select anti-cancer drugs. (Completed) III. To determine
the objective response rates (ORR; complete response + partial response) in pediatric
patients with advanced solid tumors, non-Hodgkin lymphomas, and histiocytic disorders
harboring a priori specified genomic alterations treated with pathway-targeting agents.
SECONDARY OBJECTIVES:
I. To estimate the progression free survival in pediatric patients receiving targeted
therapies for advanced solid tumors, non-Hodgkin lymphomas, and histiocytic disorders.
II. To obtain preliminary or additional information about the tolerability of targeted
therapies in children with advanced cancers.
III. To provide preliminary estimates of the pharmacokinetics of targeted therapies in
children with advanced cancers.
IV. To obtain preliminary information on the response rate to targeted therapy in patients
whose tumors lack actionable alterations as defined for the molecular analysis for therapy
choice (MATCH) study, for selected agents for which efficacy is observed in the primary
matched cohort.
EXPLORATORY OBJECTIVES:
I. To increase knowledge of the genomic landscape of advanced pediatric solid tumors,
non-Hodgkin lymphomas, and histiocytic disorders.
II. To describe the genomic changes that occur in advanced pediatric cancers between the time
of initial diagnosis and relapse, in cases for which paired tumor specimens are available.
III. To explore approaches to diagnosing and profiling genomics of advanced pediatric cancers
through evaluation of circulating tumor deoxyribonucleic acid (DNA).
IV. To determine the frequency and spectrum of germline cancer susceptibility mutations in
children with relapsed solid tumors and non-Hodgkin lymphomas and assess the feasibility of
return of those results in the National Clinical Trial Network (NCTN) group setting.
OUTLINE:
STEP 1 (SCREENING): Patients undergo biopsy along with tumor mutational screening of the
biopsy material for specific, pre-defined mutations, amplifications, or translocations of
interest via tumor sequencing and immunohistochemistry. Patients also undergo collection of
blood samples for research purposes.
STEP 2 (TREATMENT): Patients with a mutation targeted by one or more of the investigational
drugs used in this study or those without mutations are assigned to 1 of 10 treatment
subprotocols.
APEC1621A: Patients with a NTRK1, NTRK2, or NTRK3 gene fusion receive larotrectinib sulfate
orally (PO) or via nasogastric- or gastric-tube twice daily (BID) on days 1-28. Cycles repeat
every 28 days for 2 years in the absence of disease progression or unacceptable toxicity.
APEC1621B: Patients with a FGFR1, FGFR2, FGFR3, or FGFR4 gene mutation receive erdafitinib PO
once daily (QD) on days 1-28 of each cycle. Treatment repeats every 28 days for up to 26
cycles (2 years) in the absence of disease progression or unacceptable toxicity. Patients
undergo an x-ray, computed tomography (CT scan), magnetic resonance imaging (MRI),
radionuclide imaging, and/or bone scan, as well as a bone marrow aspiration and/or biopsy
during screening and on study. Patients also undergo blood sample collection on study.
APEC1621C: Patients with an EZH2, SMARCB1, or SMARCA4 gene mutation receive tazemetostat PO
BID on days 1-28. Cycles repeat every 28 days for 2 years in the absence of disease
progression or unacceptable toxicity.
APEC1621D: Patients with a TSC1, TSC2, or PI3K/mTOR gene mutations receive PI3K/mTOR
inhibitor LY3023414 PO BID on days 1-28. Cycles repeat every 28 days for 2 years in the
absence of disease progression or unacceptable toxicity.
APEC1621E: Patients with an activating MAPK pathway gene mutation receive selumetinib sulfate
PO BID on days 1-28. Cycles repeat every 28 days for 2 years in the absence of disease
progression or unacceptable toxicity.
APEC1621F: Patients with an ALK or ROS1 gene alteration receive ensartinib (ALK Inhibitor
X-396) PO BID on days 1-28. Cycles repeat every 28 days for 2 years (up to 26 cycles) in the
absence of disease progression or unacceptable toxicity. Patients undergo an x-ray, CT scan,
MRI, PET scan, radionuclide imaging, and/or bone scan, as well as a bone marrow aspiration
and/or biopsy during screening and on study. Patients also undergo blood sample collection on
study.
APEC1621G: Patients with a BRAF V600 gene mutation receive vemurafenib PO BID on days 1-28.
Cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable
toxicity.
APEC1621H: Patients with deleterious ATM, BRCA1, BRCA2, RAD51C, or RAD51D gene mutations
receive olaparib PO BID on days 1-28. Cycles repeat every 28 days for 2 years in the absence
of disease progression or unacceptable toxicity.
APEC1621I: Patients with Rb positive advanced solid tumors, non-Hodgkin lymphoma, or
histiocytic disorders with activating alterations in cell cycle genes receive palbociclib PO
QD on days 1-21. Cycles repeat every 28 days for up to 2 years in the absence of disease
progression or unacceptable toxicity.
APEC1621J: Patients with MAPK Pathway Mutations receive ulixertinib PO BID. Cycles repeat
every 28 days for up to 2 years in the absence of disease progression or unacceptable
toxicity.
APEC1621M: Patients with HRAS gene alterations receive tipifarnib PO or via nasogastric or
gastric tube BID on days 1-7 and 15-21. Treatment repeats every 28 days for up to 26 cycles
(2 years) in the absence of disease progression or unacceptable toxicity.
APEC1621N: Patients with activating RET gene alterations receive selpercatinib PO BID on days
1-28. Treatment repeats every 28 days for up to 26 cycles (2 years) in the absence of disease
progression or unacceptable toxicity. Patients may also undergo PET, CT, MRI, PET/CT,
PET/MRI, and/or CT/MRI, scintigraphy, and x-ray imaging throughout the trial.
After completion of study treatment, patients are followed up periodically.