Clinical Trials /

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)

NCT03213652

Description:

This phase II Pediatric MATCH 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 or do not respond to treatment and have spread to other places in the body. Ensartinib may stop the growth of tumor 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: Pediatric MATCH: Ensartinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With ALK or ROS1 Genomic Alterations
  • Official 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

Clinical Trial IDs

  • ORG STUDY ID: NCI-2017-01243
  • SECONDARY ID: NCI-2017-01243
  • SECONDARY ID: APEC1621F
  • SECONDARY ID: APEC1621F
  • SECONDARY ID: APEC1621F
  • SECONDARY ID: U10CA180886
  • NCT ID: NCT03213652

Conditions

  • Advanced Malignant Solid Neoplasm
  • ALK Fusion Protein Expression
  • ALK Gene Mutation
  • ALK Gene Translocation
  • Histiocytosis
  • Recurrent Childhood Central Nervous System Neoplasm
  • Recurrent Childhood Non-Hodgkin Lymphoma
  • Recurrent Malignant Solid Neoplasm
  • Recurrent Neuroblastoma
  • Refractory Central Nervous System Neoplasm
  • Refractory Malignant Solid Neoplasm
  • Refractory Neuroblastoma
  • Refractory Non-Hodgkin Lymphoma
  • ROS1 Fusion Positive
  • ROS1 Gene Mutation
  • ROS1 Gene Translocation
  • Stage III Childhood Non-Hodgkin Lymphoma
  • Stage IV Childhood Non-Hodgkin Lymphoma

Interventions

DrugSynonymsArms
EnsartinibX-396Treatment (ensartinib)

Purpose

This phase II 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 or do not respond to treatment and have spread to other places in the body. Ensartinib may stop the growth of tumor 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 ALK inhibitor X-396 (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.

      TERTIARY 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. Courses repeat every 28
      days for 2 years in the absence of disease progression or unacceptable toxicity.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (ensartinib)ExperimentalPatients receive ensartinib PO QD on days 1-28. Courses repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity.
  • Ensartinib

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 APEC1621F based on the
             presence of an actionable mutation

          -  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 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 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 hst 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, 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

               -  Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving
                  platelet transfusions for at least 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 or

          -  A serum creatinine based on age/gender as follows:

               -  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

          -  Serum glutamic pyruvic 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

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

Primary Outcome Measures

Measure:Objective response rate
Time Frame:Up to 4 years
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Incidence of toxicity evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
Time Frame:Up to 4 years
Safety Issue:
Description:All patients who receive at least one dose of protocol therapy will be considered in the evaluation of toxicity. Toxicity tables will be constructed to summarize the observed incidence by type of toxicity and grade. 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 disease progression or disease recurrence or death from any cause, assessed up to 4 years
Safety Issue:
Description:PFS along with the confidence intervals will be estimated using the Kaplan-Meier method.

Details

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

Last Updated

September 4, 2017