This trial is a multi-center, non-randomized, open-label Phase I/II study evaluating the feasibility and efficacy of vincristine, irinotecan, temozolomide, and atezolizumab in children with relapsed/refractory solid tumors.
Signed informed consent
Relapsed or refractory solid tumor after at least one prior course of therapy.
Hodgkin lymphoma or non-Hodgkin lymphoma are not permitted.
Patients with CNS malignancy or asymptomatic CNS metastases may be enrolled, provided all of the following criteria are met.
Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within 5 months after the final dose of study treatment
Women of childbearing potential must have a negative serum pregnancy test result within 21 days prior to initiation of study treatment.
Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study.
Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.
Single group
Atezolizumab
DrugFeasibility and RMS Cohorts: Administered at 15 mg/kg (max 1,200 mg) IV on Day 1 of each 21-day cycle
Vincristine
DrugFeasibility and RMS Cohorts: Administered at 1.5 mg/m\^2 (max 2 mg) IV on Day 1 of each 21-day cycle
Irinotecan
DrugFeasibility and RMS Cohorts: Administered at 50 mg/m2 IV on Days 1-5 of each 21-day cycle
Temozolomide
DrugFeasibility and RMS Cohorts: Administered at 100 mg/m\^2 (max 200 mg) IV or PO 1 hour before irinotecan injection on Days 1-5 if each 21-day cycle
Number of participants with Dose-limiting Toxicities (DLTs)
DLT is defined as any event that is possibly, probably, or definitely attributable to the treatment regimen and exceeds the protocol defined threshold for severity
Number of participants with Acute Adverse Events (AEs)
AE is defined as any untoward or unfavorable medical occurrence in a human research study participant, including any abnormal sign, symptom, clinical event, or disease, temporally associated with the subject's participation in the research, whether or not it is considered related to the subject's participation in the research. AEs will be graded by a numerical score according to the defined NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0. Adverse events not specifically defined in the NCI CTCAE will be scored on the Adverse Event log according to the general guidelines provided by the NCI CTCAE. Acute AEs are events occurring in the time period from the signing of the informed consent, through 42 days post treatment.
Number of participants with Serious Adverse Events (SAEs)
SAEs are those events, occurring at any dose, which meets any of the following criteria: 1) results in death, 2) is life-threatening, 3) results in inpatient hospitalization or prolongation of existing hospitalization, 4) results in a persistent or significant disability/incapacity, 5) results in a congenital anomly/birth defect in a neonate/infant born to a mother exposed to the IMP; or 6) based upon appropriate medical judgement, may jeopardize the subject's health and may require medical or surgical intervention to prevent one of the other outcomes listed in this definition. SAE determination does not require the event to be related to the research. SAEs will be graded by a numerical score according to the defined NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0. Serious adverse events not specifically defined in the NCI CTCAE will be scored on the Adverse Event log according to the general guidelines provided by the NCI CTCAE.
Objective response rate (ORR)
ORR is the percentage of participants whose confirmed best overall response was either a partial response (PR) or a complete response (CR) based upon independent review and per RECIST v1.1, modified INRC, or RANO criteria as appropriate.
Duration of response
Measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started)
Duration of response
Measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started)
Duration of response
Measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started)
Progression-free survival (PFS)
PFS is defined as the interval between the first day of treatment and the date of disease progression or death due to any cause, whichever occurred first (taking as reference for progressive disease the smallest measurements recorded since the treatment started).
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