This is a single center, dose-toleration study designed to investigate and determine the maximum tolerated dose of nanoliposomal irinotecan in adults with recurrent high-grade glioma when administered directly into the tumor using a process called convection-enhanced delivery (CED).
PRIMARY OBJECTIVE: I. To determine the safety and tolerability of liposomal-irinotecan with gadolinium given by intra tumoral real-time convection enhanced delivery in patients with recurrent high grade glioma (HGG). SECONDARY OBJECTIVES: I. To optimize the magnetic resonance image-guided intracranial injection procedure in patients with recurrent HGG by correlating the observed distribution of gadolinium to pre-treatment modeling of the drug distribution utilizing predictive imaging software. EXPLORATORY OBJECTIVES: I. To estimate the time to progression and overall survival measured from the date of CED. II. To determine the objective tumor response rate, based upon MR imaging, every 8 weeks for first year and then every 12 weeks. III. To evaluate the possible effect on tumor histology, as assessed by comparing pre-treatment tumor samples to post-treatment tumor samples in patients who undergo subsequent repeat surgical procedures for progression after being treated as part of this protocol. IV. Pharmacokinetics measurements will also be taken at pre-dose, 1 day after the drug is administered, and 1 week post-op. OUTLINE: Participants will be enrolled in a 3+3 dose escalation model with a two cohort concentration escalation, enrolling at least 3 patients in each cohort which results in each total dose personalized for each participant as all participants will have different size and morphology of tumors requiring different volumes of study infusions ranging from 3 mL for smallest tumor to approximately 17 mL for largest tumor (4 cm). Enrollment into a subsequent cohort will not start until after 30 days after monitoring all patients in cohort prior. Participants will be followed for 12 months from CED procedure or until death or institution of alternate anti-neoplastic therapy for progressive recurrent HGG.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
18
The drug named here (nanoliposomal irinotecan) will be used in varying amounts, based on tumor volume.
University of California, San Francisco
San Francisco, California, United States
Maximum tolerated dose
Dose limiting toxicity (DLT) will be defined as any grade-3 or higher neurological toxicity felt to be attributable to the CED infusion of liposomal-irinotecan with gadolinium, as well as any systemic grade-3 or higher hematologic or non-hematologic toxicity (after maximal medical management of nausea/vomiting/diarrhea), over a period of 30 days after CED infusion.
Time frame: 30 days post-infusion
Progression-Free Survival (PFS) at 6 months
Number of patients not having objective progression or death at 6 months after the time from date of study enrollment estimated from the PFS distribution. For patients who are not known to have died or progressed as of the data-inclusion cut-off date, PFS time will be censored at the date of the last objective progression-free disease assessment prior to the date of any subsequent systematic anticancer therapy. PFS will be summarized using Kaplan Meier methods and displayed graphically. The median event time and two-sided 95% confidence interval for the median will be reported.
Time frame: Up to 6 months
Progression-Free Survival (PFS)
The time from the date of study enrollment to the date of first observation of objective progression or death from any cause, whichever occurs first. For patients who are not known to have died or progressed as of the data-inclusion cut-off date, PFS time will be censored at the date of the last objective progression-free disease assessment prior to the date of any subsequent systematic anticancer therapy. PFS will be summarized using Kaplan Meier methods and displayed graphically. The median event time and two-sided 95% confidence interval for the median will be reported.
Time frame: Up to 10 years
Overall Survival at 12 months
The time from the date of study enrollment to the date of death from any cause. For patients who are not known to have died as of the 12 month cut-off date, survival time will be censored at the date of the last known survival status of participant prior to the date of any subsequent systematic anticancer therapy. OS will be summarized using Kaplan Meier methods and displayed graphically. The median event time and two-sided 95% confidence interval for the median will be reported.
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Time frame: Up to 12 months
Overall Survival (OS)
The time from the date of study enrollment to the date of death from any cause. For patients who are not known to have died as of the data-inclusion cut-off date, survival time will be censored at the date of the last known survival status of participant prior to the date of any subsequent systematic anticancer therapy. OS will be summarized using Kaplan Meier methods and displayed graphically. The median event time and two-sided 95% confidence interval for the median will be reported.
Time frame: Up to 10 years
Objective Tumor Response Rate
Overall response rate (ORR) is the proportion of patients who achieved a complete response (CR) or partial response (PR) out of all randomly assigned patients. Based on Response assessment in neuro-oncology criteria (RANO), a responder is defined by radiographic and clinical criteria. Complete response or PR will be first assessed by radiographic changes as determined by an improvement of the bi-dimensional evaluation of the tumor size. In addition, changes in neurologic function and steroid use will be considered to determine stable disease (SD). The objective response rate (ORR) will be summarized with the corresponding exact two-sided 95% confidence interval calculated using a method based on the F distribution
Time frame: Up to 10 years