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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)

PHASE2RECRUITING

This phase II Pediatric MATCH treatment trial studies how well ensartinib works in treating patients with solid tumors, non-Hodgkin lymphoma, or histiocytic disorders with ALK or ROS1 genomic alterations that have come back (recurrent) or does not respond to treatment (refractory) and may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Ensartinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

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Study details:

PRIMARY OBJECTIVE:. I. To determine the objective response rate (ORR; complete response + partial response) in pediatric patients treated with ensartinib with advanced solid tumors (including central nervous system \[CNS\] tumors), non-Hodgkin lymphomas or histiocytic disorders that harbor ALK or ROS1 fusions or that harbor ALK missense mutations.

SECONDARY OBJECTIVES:. I. To estimate the progression free survival in pediatric patients treated with ensartinib with advanced solid tumors (including CNS tumors), non-Hodgkin lymphomas or histiocytic disorders that harbor ALK or ROS1 fusions or that harbor ALK missense mutations.

II. To obtain information about the tolerability of ensartinib in children with relapsed or refractory cancer. III.

To provide preliminary estimates of the pharmacokinetics of ensartinib in children with relapsed or refractory cancer. EXPLORATORY OBJECTIVES:. I.

To evaluate other biomarkers as predictors of response to ensartinib and specifically, whether tumors that harbor different missense mutations or fusions (including the crizotinib resistant F1174L ALK variant) will demonstrate differential response to ensartinib treatment. II. To explore approaches to profiling changes in tumor genomics over time through evaluation of circulating tumor deoxyribonucleic acid (DNA).

OUTLINE:. Patients receive ensartinib orally (PO) once daily (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, 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 for 30 days.

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Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

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.

Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients =< 16 years of age.

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.

For patients with solid tumors without known bone marrow involvement: Peripheral absolute neutrophil count (ANC) >= 1000/mm^3 (within 7 days prior to enrollment) and 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).

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

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

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

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

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Eligibility

Age eligible for study : 12 and older

Healthy volunteers accepted : No

Gender eligible for study: All

Things to know

Study dates

Study start: 2018-04-17

Primary completion: 2027-09-30

Study completion finish: 2027-09-30

Study type

TREATMENT

Phase

PHASE2

Trial ID

NCT03213652

Intervention or treatment

PROCEDURE: Biospecimen Collection

PROCEDURE: Bone Marrow Aspiration and Biopsy

PROCEDURE: Bone Scan

PROCEDURE: Computed Tomography

DRUG: Ensartinib

OTHER: Laboratory Biomarker Analysis

PROCEDURE: Magnetic Resonance Imaging

OTHER: Pharmacological Study

PROCEDURE: Positron Emission Tomography

PROCEDURE: Radionuclide Imaging

PROCEDURE: X-Ray Imaging

Conditions

• Advanced Malignant Solid Neoplasm
• Malignant Solid Neoplasm
• Recurrent Ependymoma
• Recurrent Hepatoblastoma
• Recurrent Langerhans Cell Histiocytosis
• Recurrent Malignant Germ Cell Tumor
• Recurrent Malignant Glioma
• Recurrent Malignant Solid Neoplasm
• Recurrent Medulloblastoma
• Recurrent Neuroblastoma
• Recurrent Non-Hodgkin Lymphoma
• Recurrent Osteosarcoma
• Recurrent Primary Central Nervous System Neoplasm
• Recurrent Rhabdoid Tumor
• Recurrent Soft Tissue Sarcoma
• Refractory Hepatoblastoma
• Refractory Langerhans Cell Histiocytosis
• Refractory Malignant Germ Cell Tumor
• Refractory Malignant Solid Neoplasm
• Refractory Medulloblastoma
• Refractory Neuroblastoma
• Refractory Non-Hodgkin Lymphoma
• Refractory Osteosarcoma
• Refractory Primary Central Nervous System Neoplasm
• Refractory Rhabdoid Tumor
• Refractory Rhabdomyosarcoma
• Wilms Tumor
• Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor
• Recurrent Rhabdomyosarcoma
• Refractory Ependymoma
• Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor
• Refractory Malignant Glioma
• Refractory Soft Tissue Sarcoma

Image related to Advanced Malignant Solid Neoplasm

Condition: Advanced Malignant Solid Neoplasm, Malignant Solid Neoplasm and more
PROCEDURE: Biospecimen Collection and other drugs
Perth, Western Australia, Australia
Sponsor: National Cancer Institute (NCI)

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Find a site

Closest Location:

Perth Children's Hospital

Research sites nearby

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Perth Children's Hospital
Perth, Western Australia, Australia

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Participant Group/Arm	Intervention/Treatment
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.	PROCEDURE: Biospecimen Collection Undergo blood sample collection

Participant Group/Arm

Intervention/Treatment

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.

PROCEDURE: Biospecimen Collection

Undergo blood sample collection

What is the study measuring?

Primary outcome

Primary Outcome Measure	Primary Outcome Description	Primary Outcome Time Frame
Objective response rate	A responder is defined as a patient who achieves a best response of partial response or complete response on the study. 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.	From enrollment to the end of treatment, up to 2 years

Secondary outcome

Secondary Outcome Measure	Secondary Outcome Description	Secondary Outcome Time Frame
Percentage of patients experiencing grade 3 or higher adverse events	Percentage of patients experiencing grade 3 or higher adverse events will be evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. All patients who receive at least one dose of protocol therapy will be considered in the evaluation of toxicity.	From enrollment to the end of treatment, up to 2 years
Progression free survival (PFS)	Progression free survival will be defined as time 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. PFS along with the confidence intervals will be estimated using the Kaplan-Meier method.	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
Pharmacokinetic (PK) parameters	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).	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

Frequently Asked Questions

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References

Clinical Trials Gov: 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)