Clinical Trials /

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)

NCT03210714

Description:

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.

Related Conditions:
  • Histiocytic and Dendritic Cell Neoplasm
  • Malignant Solid Tumor
  • Non-Hodgkin Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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)
  • Official Title: NCI-COG Pediatric MATCH (Molecular Analysis for Therapy Choice) - Phase 2 Subprotocol of JNJ-42756493 (Erdafitinib) in Patients With Tumors Harboring FGFR1/2/3/4 Alterations

Clinical Trial IDs

  • ORG STUDY ID: NCI-2017-01159
  • SECONDARY ID: NCI-2017-01159
  • SECONDARY ID: APEC1621B
  • SECONDARY ID: APEC1621B
  • SECONDARY ID: U10CA180886
  • SECONDARY ID: UM1CA081457
  • NCT ID: NCT03210714

Conditions

  • Advanced Malignant Solid Neoplasm
  • Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma
  • Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma
  • FGFR1 Gene Mutation
  • FGFR2 Gene Mutation
  • FGFR3 Gene Mutation
  • FGFR4 Gene Mutation
  • Histiocytosis
  • Low Grade Glioma
  • Malignant Glioma
  • Recurrent Central Nervous System Neoplasm
  • Recurrent Childhood Ependymoma
  • Recurrent Childhood Malignant Germ Cell Tumor
  • Recurrent Childhood Medulloblastoma
  • Recurrent Childhood Non-Hodgkin Lymphoma
  • Recurrent Childhood Rhabdomyosarcoma
  • Recurrent Childhood Soft Tissue Sarcoma
  • Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor
  • Recurrent Hepatoblastoma
  • Recurrent Langerhans Cell Histiocytosis
  • Recurrent Malignant Solid Neoplasm
  • Recurrent Neuroblastoma
  • Recurrent Osteosarcoma
  • Refractory Central Nervous System Neoplasm
  • Refractory Langerhans Cell Histiocytosis
  • Refractory Malignant Solid Neoplasm
  • Refractory Neuroblastoma
  • Refractory Non-Hodgkin Lymphoma
  • Rhabdoid Tumor
  • Stage III Soft Tissue Sarcoma AJCC v7
  • Stage IV Soft Tissue Sarcoma AJCC v7
  • Wilms Tumor

Interventions

DrugSynonymsArms
ErdafitinibJNJ-42756493Treatment (erdafitinib)

Purpose

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.

Detailed Description

      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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (erdafitinib)ExperimentalPatients receive erdafitinib PO QD on days 1-28. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.
  • Erdafitinib

Eligibility Criteria

        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
      
Maximum Eligible Age:21 Years
Minimum Eligible Age:12 Months
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Response rate
Time Frame:3 years
Safety Issue:
Description:Response rates will be calculated as the percent of evaluable patients who are responders, and confidence intervals will be constructed using the Wilson score interval method.

Secondary Outcome Measures

Measure:Incidence of adverse events
Time Frame:Up to 3 years
Safety Issue:
Description:Graded by National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Toxicity tables will be constructed to summarize the observed incidence by type of toxicity and grade. A patient will be counted only once for a given toxicity for the worst grade of that toxicity reported for that patient. Toxicity information recorded will include the type, severity, time of onset, time of resolution, and the probable association with the study regimen.
Measure:Progression free survival (PFS)
Time Frame:From the initiation of protocol treatment to the occurrence of any of the following events: disease progression or disease recurrence or death from any cause, assessed up to 3 years
Safety Issue:
Description:PFS along with the confidence intervals will be estimated using the Kaplan-Meier method.
Measure:Pharmacokinetic (PK) parameters
Time Frame:Course 2 day 1
Safety Issue:
Description:A descriptive analysis of PK parameters will be performed to define systemic exposure, drug clearance, and other pharmacokinetic parameters. The PK parameters will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit).

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:National Cancer Institute (NCI)

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