IRB Study Number 17-1081
Status Recruiting
Institute Taussig Cancer Institute
Description
1.1 Primary Objectives
To determine the objective response rate (ORR; complete response + partial response) 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.
1.2 Secondary Aims
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.
To obtain information about the tolerability of ensartinib in children with relapsed or refractory cancer.
To provide preliminary estimates of the pharmacokinetics of ensartinib in children with relapsed or refractory cancer.
Inclusion Criteria
APEC1621SC: Patient must have enrolled onto APEC1621SC and must have been given a treatment assignment to MATCH to APEC1621F based on the presence of an actionable mutation as defined in APEC1621SC. Examples of actionable mutations for APEC1621F are listed in Appendix VII-A and Appendix VII-B.
Age: Patients must be than 12 months and 21 years of age at the time of study enrollment.
BSA: Patients must have a body surface area ≥ 0.5 m2 at enrollment.
Disease Status:
Patients must have radiographically measurable disease (See Section 12) at the time of study enrollment. Patients with neuroblastoma who do not have measurable disease but have MIBG+ 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 PET scans) except as noted for neuroblastoma
elevated tumor markers in plasma or CSF
previously radiated lesions that have not demonstrated clear progression post radiation
leptomeningeal lesions that do not meet the measurement requirements for RECIST 1.1.
Performance Level: Karnofsky 50% for patients > 16 years of age and Lansky 50 for patients 16 years of age (See Appendix I). 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.
Prior Therapy
4.1.6.1 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.
a. Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive. See https://www.cogmembers.org/site/disc/devtherapeutics/default.aspx for commercial and Phase 1 investigational agent classifications. For agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned Research Coordinator prior to enrollment.
i. ≥ 21 days after the last dose of cytotoxic or myelosuppressive chemotherapy (42 days if prior nitrosourea).
b. Anti-cancer agents not known to be myelosuppressive (e.g. not associated with reduced platelet or ANC counts): ≥ 7 days after the last dose of agent. See https://www.cogmembers.org/site/disc/devtherapeutics/default.aspx for commercial and Phase 1 investigational agent classifications. For agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned Research Coordinator prior to enrollment.
c. 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.
d. Corticosteroids: See Section 4.2.2.1. If used to modify immune adverse events related to prior therapy, ≥ 14 days must have elapsed since last dose of corticosteroid.
e. 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.
f. Interleukins, Interferons and Cytokines (other than hematopoetic growth factors): ≥ 21 days after the completion of interleukins, interferon or cytokines (other than hematopoetic growth factors)
g. Stem cell Infusions (with or without TBI):
Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including DLI or boost infusion: ≥ 84 days after infusion and no evidence of GVHD.
Autologous stem cell infusion including boost infusion: ≥ 42 days.
h. Cellular Therapy: ≥ 42 days after the completion of any type of cellular therapy (e.g., modified T cells, NK cells, dendritic cells, etc.)
i. 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 BM radiation. Note: Radiation may not be delivered to “measurable disease” tumor site(s) being used to follow response to subprotocol treatment.
j. Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131IMIBG): ≥ 42 days after systemically administered radiopharmaceutical therapy.
k. 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.
Organ Function Requirements
Adequate Bone Marrow Function Defined as:
a. For patients with solid tumors without known bone marrow involvement:
Peripheral absolute neutrophil count (ANC) 1000/mm3
Platelet count 100,000/mm3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
b. Patients with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts in 4.1.7.1.a (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.
Adequate Renal Function Defined as:
Creatinine clearance or radioisotope GFR 70ml/min/1.73 m2 or
A serum creatinine based on age/gender as follows: (See protocol)
Adequate Liver Function Defined as:
Bilirubin (sum of conjugated + unconjugated) 1.5 x upper limit of normal (ULN) for age
SGPT (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.
Informed Consent: 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
Pregnancy or Breast-Feeding
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 (See Section 4.1.6.1.d).
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.
4.2.2.5 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. See Appendix II for a list of agents. Note: CYP3A4 inducing anti-epileptic drugs and dexamethasone for CNS tumors or metastases, on a stable dose, are allowed.
Infection: 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.
