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)
|
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT03210714 |
|
Recruitment Status :
Active, not recruiting
First Posted : July 7, 2017
Last Update Posted : April 26, 2023
|
Sponsor:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
National Cancer Institute (NCI)
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
Brief Summary:
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 with FGFR mutations by blocking some of the enzymes needed for cell growth.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Advanced Malignant Solid Neoplasm Recurrent Childhood Ependymoma Recurrent Childhood Malignant Germ Cell Tumor Recurrent Childhood Medulloblastoma Recurrent Childhood Non-Hodgkin Lymphoma Recurrent Childhood Osteosarcoma Recurrent Childhood Rhabdomyosarcoma Recurrent Childhood Soft Tissue Sarcoma Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor Recurrent Hepatoblastoma Recurrent Langerhans Cell Histiocytosis Recurrent Malignant Glioma Recurrent Malignant Solid Neoplasm Recurrent Neuroblastoma Recurrent Primary Central Nervous System Neoplasm Recurrent Rhabdoid Tumor Refractory Childhood Malignant Germ Cell Tumor Refractory Childhood Osteosarcoma Refractory Childhood Rhabdomyosarcoma Refractory Childhood Soft Tissue Sarcoma Refractory Ependymoma Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor Refractory Hepatoblastoma Refractory Langerhans Cell Histiocytosis Refractory Malignant Glioma Refractory Malignant Solid Neoplasm Refractory Medulloblastoma Refractory Neuroblastoma Refractory Non-Hodgkin Lymphoma Refractory Primary Central Nervous System Neoplasm Refractory Rhabdoid Tumor Wilms Tumor | Procedure: Biospecimen Collection Procedure: Bone Marrow Aspiration and Biopsy Procedure: Bone Scan Procedure: Computed Tomography Drug: Erdafitinib Other: Laboratory Biomarker Analysis Procedure: Magnetic Resonance Imaging Other: Pharmacological Study Procedure: Positron Emission Tomography Procedure: Radionuclide Imaging Procedure: X-Ray Imaging | Phase 2 |
PRIMARY OBJECTIVE:
I. To determine the objective response rate (ORR; complete response + partial response) in pediatric patients treated with 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 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 erdafitinib in children with relapsed or refractory cancer.
III. To provide preliminary estimates of the pharmacokinetics of erdafitinib in children with relapsed or refractory cancer.
EXPLORATORY OBJECTIVE:
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 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), positron emission tomography (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.
After completion of study treatment, patients are followed up periodically.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 49 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | NCI-COG Pediatric MATCH (Molecular Analysis for Therapy Choice) - Phase 2 Subprotocol of Erdafitinib in Patients With Tumors Harboring FGFR1/2/3/4 Alterations |
| Actual Study Start Date : | November 6, 2017 |
| Estimated Primary Completion Date : | December 31, 2024 |
| Estimated Study Completion Date : | December 31, 2024 |
Resource links provided by the National Library of Medicine
Drug Information available for:
Erdafitinib
Genetic and Rare Diseases Information Center resources:
Lymphosarcoma
Soft Tissue Sarcoma
Glioma
Ependymoma
Malignant Germ Cell Tumor
Osteosarcoma
Neuroepithelioma
Medulloblastoma
Rhabdoid Tumor
Ewing Sarcoma
Langerhans Cell Histiocytosis
Neuroblastoma
Hepatoblastoma
Wilms' Tumor
Medulloblastoma, Childhood
| Arm | Intervention/treatment |
|---|---|
|
Experimental: Treatment (erdafitinib)
Patients receive erdafitinib PO 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, 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.
|
Procedure: Biospecimen Collection
Undergo blood sample collection
Other Names:
Procedure: Bone Marrow Aspiration and Biopsy Undergo a bone marrow aspiration and/or biopsy Procedure: Bone Scan Undergo a bone scan
Other Name: Bone Scintigraphy Procedure: Computed Tomography Undergo a CT scan
Other Names:
Drug: Erdafitinib Given PO
Other Names:
Other: Laboratory Biomarker Analysis Correlative studies Procedure: Magnetic Resonance Imaging Undergo MRI
Other Names:
Other: Pharmacological Study Correlative studies Procedure: Positron Emission Tomography Undergo a PET scan
Other Names:
Procedure: Radionuclide Imaging Undergo radionuclide imaging
Other Names:
Procedure: X-Ray Imaging Undergo an x-ray
Other Names:
|
Primary Outcome Measures :
- Response rate [ Time Frame: From enrollment to the end of treatment, up to 2 years ]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 :
- Incidence of adverse events [ Time Frame: From enrollment to the end of treatment, up to 2 years ]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.
- 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 ]PFS along with the confidence intervals will be estimated using the Kaplan-Meier method.
- Pharmacokinetic (PK) parameters [ Time Frame: Cycle 2 day 1 ]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).
Other Outcome Measures:
- Changes in tumor genomic profile [ Time Frame: Up to 3 years ]A descriptive analysis will be performed and will be summarized with simple summary statistics. All of these analyses will be descriptive in nature.
Information from the National Library of Medicine
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 12 Months to 21 Years (Child, Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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 as defined in APEC1621SC
- Patients must be >/= 12 months and =/< 21 years of age at the time of study enrollment
- 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 lesion that is at minimum 10 mm in one dimension on standard MRI or CT
-
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 relatively 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 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 (performed within 7 days prior to enrollment)
- Platelet count >/= 100,000/mm^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) (performed within 7 days prior to enrollment)
- Hemoglobin >/= 8.0 g/dL at baseline (may receive red blood cell [RBC] transfusions) (performed within 7 days prior to enrollment)
- 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 (performed within 7 days prior to enrollment):
- 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 (performed within 7 days prior to enrollment)
- 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) (performed within 7 days prior to enrollment)
- Serum albumin >/= 2 g/dL (performed within 7 days prior to enrollment)
- 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 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 3 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 strong inducers or moderate inhibitors of CYP2C9 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 II-IV 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 significant ophthalmologic conditions (uncontrolled glaucoma, central serous retinopathy, history of retinal vein occlusion or retinal detachment, excluding patients with longstanding findings secondary to existing conditions) are not eligible, to be confirmed with baseline ophthalmologic exam; all patients must have a baseline ophthalmologic exam, including fundoscopy to confirm no significant ophthalmologic conditions are present
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03210714
Locations
Show 118 study locations
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
| Principal Investigator: | Alice Lee | Children's Oncology Group |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT03210714 |
| Other Study ID Numbers: |
NCI-2017-01159 NCI-2017-01159 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) APEC1621B ( Other Identifier: Children's Oncology Group ) APEC1621B ( Other Identifier: CTEP ) U10CA180886 ( U.S. NIH Grant/Contract ) UM1CA081457 ( U.S. NIH Grant/Contract ) |
| First Posted: | July 7, 2017 Key Record Dates |
| Last Update Posted: | April 26, 2023 |
| Last Verified: | April 2023 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
|
Lymphoma Neoplasms Sarcoma Lymphoma, Non-Hodgkin Glioma Neuroblastoma Neoplasms, Germ Cell and Embryonal Osteosarcoma Rhabdomyosarcoma Ependymoma Sarcoma, Ewing Medulloblastoma Neuroectodermal Tumors Neuroectodermal Tumors, Primitive Wilms Tumor |
Rhabdomyosarcoma, Embryonal Neuroectodermal Tumors, Primitive, Peripheral Rhabdoid Tumor Nervous System Neoplasms Hepatoblastoma Central Nervous System Neoplasms Histiocytosis, Langerhans-Cell Histiocytosis Recurrence Neoplasms by Histologic Type Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Disease Attributes |