NCI-COG Pediatric MATCH (Molecular Analysis for Therapy Choice)- Phase 2 Subprotocol of Ensartinib in Patients With Tumors Harboring ALK or ROS1 Genomic Alterations
Overview
- Phase
- Phase 2
- Intervention
- Biospecimen Collection
- Conditions
- Advanced Malignant Solid Neoplasm
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 13
- Locations
- 252
- Primary Endpoint
- Objective response rate
- Status
- Active, not recruiting
- Last Updated
- 19 days ago
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Eligibility Criteria
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
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
Arms & Interventions
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.
Intervention: Biospecimen Collection
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.
Intervention: Bone Marrow Aspiration and Biopsy
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.
Intervention: Bone Scan
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.
Intervention: Computed Tomography
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.
Intervention: Laboratory Biomarker Analysis
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.
Intervention: Positron Emission Tomography
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.
Intervention: Radionuclide Imaging
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.
Intervention: X-Ray Imaging
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.
Intervention: Pharmacological Study
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.
Intervention: Ensartinib
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.
Intervention: Magnetic Resonance Imaging
Outcomes
Primary Outcomes
Objective response rate
Time Frame: Up to 2 years from study entry
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. The revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) was used to determine response and progression in this study, with specific criteria outlined for the different subtypes of tumors (e.g., 2-dimensional measurements for central nervous system (CNS) tumors).
Secondary Outcomes
- Percentage of patients experiencing grade 3 or higher adverse events(Up to 2 years from study entry)
- Percentage of patients experiencing grade 3 or higher adverse events(Up to 2 years from study entry)
- Progression free survival (PFS)(Up to 6 months from study entry)
- Pharmacokinetic (PK) parameters(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)