Trial Review

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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03213652




Registration number
NCT03213652
Ethics application status
Date submitted
10/07/2017
Date registered
11/07/2017
Date last updated
9/08/2024

Titles & IDs
Public title
Ensartinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With ALK or ROS1 Genomic Alterations (A Pediatric MATCH Treatment Trial)
Scientific title
NCI-COG Pediatric MATCH (Molecular Analysis for Therapy Choice)- Phase 2 Subprotocol of Ensartinib in Patients With Tumors Harboring ALK or ROS1 Genomic Alterations
Secondary ID [1] 0 0
NCI-2017-01243
Secondary ID [2] 0 0
NCI-2017-01243
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Malignant Solid Neoplasm 0 0
Malignant Solid Neoplasm 0 0
Recurrent Ependymoma 0 0
Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor 0 0
Recurrent Hepatoblastoma 0 0
Recurrent Langerhans Cell Histiocytosis 0 0
Recurrent Malignant Germ Cell Tumor 0 0
Recurrent Malignant Glioma 0 0
Recurrent Malignant Solid Neoplasm 0 0
Recurrent Medulloblastoma 0 0
Recurrent Neuroblastoma 0 0
Recurrent Non-Hodgkin Lymphoma 0 0
Recurrent Osteosarcoma 0 0
Recurrent Primary Central Nervous System Neoplasm 0 0
Recurrent Rhabdoid Tumor 0 0
Recurrent Rhabdomyosarcoma 0 0
Recurrent Soft Tissue Sarcoma 0 0
Refractory Ependymoma 0 0
Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor 0 0
Refractory Hepatoblastoma 0 0
Refractory Langerhans Cell Histiocytosis 0 0
Refractory Malignant Germ Cell Tumor 0 0
Refractory Malignant Glioma 0 0
Refractory Malignant Solid Neoplasm 0 0
Refractory Medulloblastoma 0 0
Refractory Neuroblastoma 0 0
Refractory Non-Hodgkin Lymphoma 0 0
Refractory Osteosarcoma 0 0
Refractory Primary Central Nervous System Neoplasm 0 0
Refractory Rhabdoid Tumor 0 0
Refractory Rhabdomyosarcoma 0 0
Refractory Soft Tissue Sarcoma 0 0
Wilms Tumor 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
Cancer 0 0 0 0
Sarcoma (also see 'Bone') - soft tissue
Cancer 0 0 0 0
Bone
Cancer 0 0 0 0
Brain
Cancer 0 0 0 0
Neuroendocrine tumour (NET)
Cancer 0 0 0 0
Children's - Other
Cancer 0 0 0 0
Ovarian and primary peritoneal
Cancer 0 0 0 0
Testicular
Cancer 0 0 0 0
Other cancer types
Cancer 0 0 0 0
Children's - Brain
Cancer 0 0 0 0
Kidney
Cancer 0 0 0 0
Liver
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Surgery - Biospecimen Collection
Treatment: Surgery - Bone Marrow Aspiration and Biopsy
Treatment: Surgery - Bone Scan
Treatment: Surgery - Computed Tomography
Treatment: Drugs - Ensartinib
Other interventions - Laboratory Biomarker Analysis
Treatment: Surgery - Magnetic Resonance Imaging
Other interventions - Pharmacological Study
Treatment: Surgery - Positron Emission Tomography
Treatment: Surgery - Radionuclide Imaging
Treatment: Surgery - X-Ray Imaging

Experimental: Treatment (ensartinib) - Patients receive ensartinib PO QD 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.


Treatment: Surgery: Biospecimen Collection
Undergo blood sample collection

Treatment: Surgery: Bone Marrow Aspiration and Biopsy
Undergo a bone marrow aspiration and/or biopsy

Treatment: Surgery: Bone Scan
Undergo a bone scan

Treatment: Surgery: Computed Tomography
Undergo a CT scan

Treatment: Drugs: Ensartinib
Given PO

Other interventions: Laboratory Biomarker Analysis
Correlative studies

Treatment: Surgery: Magnetic Resonance Imaging
Undergo MRI

Other interventions: Pharmacological Study
Correlative studies

Treatment: Surgery: Positron Emission Tomography
Undergo a PET scan

Treatment: Surgery: Radionuclide Imaging
Undergo radionuclide imaging

Treatment: Surgery: X-Ray Imaging
Undergo an x-ray
Intervention code [1] 0 0
Treatment: Surgery
Intervention code [2] 0 0
Treatment: Drugs
Intervention code [3] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Objective response rate
Timepoint [1] 0 0
From enrollment to the end of treatment, up to 2 years
Secondary outcome [1] 0 0
Percentage of patients experiencing grade 3 or higher adverse events
Timepoint [1] 0 0
From enrollment to the end of treatment, up to 2 years
Secondary outcome [2] 0 0
Progression free survival (PFS)
Timepoint [2] 0 0
From the initiation of protocol treatment to the occurrence of disease progression or disease recurrence or death from any cause, assessed up to 5 years
Secondary outcome [3] 0 0
Pharmacokinetic (PK) parameters
Timepoint [3] 0 0
Pre-dose, 1, 2, 4, 6-8, and 20-24 hours post day 1 dose and pre-dose, 1, 2, 4, and 6-8 hours post day 28 dose of cycle 1

Eligibility
Key inclusion criteria
* Patient must have enrolled onto APEC1621SC//NCI-2017-01251 and must have been given a treatment assignment to Molecular Analysis for Therapy Choice (MATCH) to APEC1621F/NCI-2017-01243 based on the presence of an actionable mutation as defined in APEC1621SC/ NCI-2017-01251
* Patients must be >= than 12 months and =< 21 years of age at the time of study enrollment.
* Patients must have a body surface area >= 0.5 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 iobenguane (MIBG) positive (+) evaluable disease are eligible; measurable disease in patients with CNS involvement is defined as any lesion that is at minimum 10 mm in one dimension on a 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 counts [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.)
* Radiation 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 none 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, 131I-MIBG): >= 42 days after systemically administered radiopharmaceutical therapy
* Patients must not have received prior exposure to ensartinib; prior treatment with other ALK inhibitors is permitted given that at least 5 half-lives or 21 days have elapsed since therapy discontinuation, whichever is greater
* For patients with solid tumors without known bone marrow involvement:

* Peripheral absolute neutrophil count (ANC) >= 1000/mm^3 (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) (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 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 (within 7 days prior to enrollment) or a serum creatinine based on age/gender as follows (within 7 days prior to enrollment):

* Age 1 to < 2 years: maximum serum creatinine 0.6 mg/dL for male and 0.6 mg/dL for female
* Age 2 to < 6 years: maximum serum creatinine 0.8 mg/dL for male and 0.8 mg/dL for female
* Age 6 to < 10 years: maximum serum creatinine 1 mg/dL for male and 1 mg/dL for female
* Age 10 to < 13 years: maximum serum creatinine 1.2 mg/dL for male and 1.2 mg/dL for female
* Age 13 to < 16 years: maximum serum creatinine 1.5 mg/dL for male and 1.4 mg/dL for female
* Age >= 16 years: maximum serum creatinine 1.7 mg/dL for male and 1.4 mg/dL for female
* Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment)
* Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L (within 7 days prior to enrollment) (for the purpose of this study, the ULN for SGPT is 45 U/L)
* Serum albumin >= 2 g/dL (within 7 days prior to enrollment)
* Patients must be able to swallow intact capsules
* 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
Minimum age
12 Months
Maximum age
21 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Pregnant or breast-feeding women will not be entered on this study because there is currently no available information regarding human fetal or teratogenic toxicities; 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 for the duration of study treatment and for one week after the last dose of ensartinib
* 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 strong inhibitors of CYP3A4 are not eligible; strong inducers or inhibitors of CYP3A4 should be avoided from 14 days prior to enrollment to the end of the study

* Note: CYP3A4 inducing anti-epileptic drugs and dexamethasone for CNS tumors or metastases, on a stable dose, are allowed
* 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

Study design
Purpose of the study
Treatment
Allocation to intervention
NA
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
17/04/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/09/2027
Actual
Sample size
Target
98
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 0 0
Perth Children's Hospital - Perth
Recruitment postcode(s) [1] 0 0
6009 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Alaska
Country [3] 0 0
United States of America
State/province [3] 0 0
Arizona
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United States of America
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Arkansas
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United States of America
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California
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Colorado
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Connecticut
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United States of America
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Delaware
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United States of America
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District of Columbia
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United States of America
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Florida
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United States of America
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Georgia
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Idaho
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Illinois
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Indiana
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Iowa
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Kentucky
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Louisiana
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Maine
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Maryland
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Massachusetts
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Michigan
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Minnesota
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Mississippi
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Missouri
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Nebraska
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Nevada
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New Jersey
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New York
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North Carolina
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North Dakota
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Ohio
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Oklahoma
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Oregon
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Pennsylvania
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South Carolina
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South Dakota
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Tennessee
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Texas
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Utah
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Vermont
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Virginia
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Washington
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West Virginia
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United States of America
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Wisconsin
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Canada
State/province [45] 0 0
Quebec
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Puerto Rico
State/province [46] 0 0
San Juan

Funding & Sponsors
Primary sponsor type
Government body
Name
National Cancer Institute (NCI)
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Children's Oncology Group
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Meredith S Irwin
Address 0 0
Children's Oncology Group
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT03213652