Study of Convection-Enhanced, Image-Assisted Delivery of Liposomal-Irinotecan In Recurrent High Grade Glioma

NCT02022644 | Completed Phase 1 DMC FDA Drug

• 5 other identifiers: Nano CED13-120255R21CA186140-02NCI-2017-0130413108
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

High Grade Glioma

Outcome Measures

Primary Outcomes (1)

• 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.

  30 days post-infusion

Secondary Outcomes (5)

• Progression-Free Survival (PFS) at 6 months

  Up to 6 months

• Progression-Free Survival (PFS)

  Up to 10 years

• Overall Survival at 12 months

  Up to 12 months

• Overall Survival (OS)

  Up to 10 years

• Objective Tumor Response Rate

  Up to 10 years

Other Outcomes (4)

• Pre-infusion modeling of the drug distribution vs. post-infusion imaging.

  Up to 48 hours pre-infusion and up to 48 hours post-infusion

• Ratio of the Volume of distribution (Vd) to volume infused (Vi)

  Up to 24 hours from time of dosing

• Change in Tumor Histology

  Up to 12 months from date of surgery

Study Arms (8)

Group 1 - 20 mg

EXPERIMENTAL

Tumor diameter: 1 cm, Tumor volume: \~0.5cm3, Infusion Volume: 2-3 ml, Irinotecan conc.: 20 mg/ml, Infusion time: 6-24 hours, no more than 48

Drug: nanoliposomal irinotecan

Group 2 - 40 mg

EXPERIMENTAL

Tumor diameter: 2 cm,Tumor volume: \~4.1cm3, Infusion Volume: 3-4 ml, Irinotecan conc.: 40 mg/ml, Infusion Time: 6-24 hours, no more than 48

Drug: nanoliposomal irinotecan

Group 3 - 140 mg

EXPERIMENTAL

Tumor diameter: 3 cm, Tumor volume: \~14cm3, Infusion Volume: 6-7 ml, Irinotecan conc.: 140 mg/ml, Infusion Time: 6-24 hours, no more than 48

Drug: nanoliposomal irinotecan

Group 4 - 340 mg

EXPERIMENTAL

Tumor diameter: 4 cm, Tumor volume: \~34cm3, Infusion Volume: ≤17 ml, Irinotecan conc.: 340 mg/ml, Infusion Time: 6-24 hours, no more than 48

Drug: nanoliposomal irinotecan

Group 5 - 40 mg

EXPERIMENTAL

Tumor diameter: 1 cm, Tumor volume: \~0.5cm3, Infusion Volume: 2-3 ml, Irinotecan conc.: 40 mg/ml, Infusion Time: 6-24 hours, no more than 48

Drug: nanoliposomal irinotecan

Group 6 - 80 mg

EXPERIMENTAL

Tumor diameter: 2 cm, Tumor volume: \~4.1cm3, Infusion Volume: 3-4 ml, Irinotecan conc.: 80 mg/ml, Infusion Time: 6-24 hours, no more than 48

Drug: nanoliposomal irinotecan

Group 7 - 280 mg

EXPERIMENTAL

Tumor diameter: 3 cm, Tumor volume: \~14cm3, Infusion Volume: 6-7 ml, Irinotecan conc.: 280 mg/ml, Infusion Time: 6-24 hours, no more than 48

Drug: nanoliposomal irinotecan

Group 8 - 680 mg

EXPERIMENTAL

Tumor diameter: 4 cm, Tumor volume: \~34cm3, Infusion Volume: ≤17 ml, Irinotecan conc.: 680 mg/ml, Infusion Time: 6-24 hours, no more than 48

Drug: nanoliposomal irinotecan

Interventions

nanoliposomal irinotecan DRUG

The drug named here (nanoliposomal irinotecan) will be used in varying amounts, based on tumor volume.

Also known as: MM-398, ONIVYDE

Group 1 - 20 mg; Group 2 - 40 mg; Group 3 - 140 mg; Group 4 - 340 mg; Group 5 - 40 mg; Group 6 - 80 mg; Group 7 - 280 mg; Group 8 - 680 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with radiographically proven recurrent, intracranial high grade glioma will be eligible for this protocol. Patients must have evidence of tumor progression as determined by the Revised Assessment in Neuro-Oncology RANO criteria following standard therapy.
• High grade glioma includes glioblastoma multiforme (GBM), Gliosarcoma (GS), anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO), anaplastic mixed oligoastrocytoma (AMO), or malignant astrocytoma not otherwise specified. (NOS)
• Magnetic resonance imaging (MRI) must be performed within 21 days prior to enrollment, and patients who are receiving steroids must be stable or decreasing for at least 5 days prior to imaging. If the steroid dose is increased between the date of imaging and enrollment, a new baseline MRI is required.
• Patients must have completed only 1 prior course of radiation therapy and must have experienced an interval of greater than 12 weeks from the completion of radiation therapy to study entry.
• Patients will be eligible if the original histology was low-grade glioma and a subsequent histological diagnosis of a high grade glioma is made.
• There is no limit as to the number of prior treatments but patients must have radiographic evidence of progressive disease
• Recurrent tumor must be a solid, single, supratentorial, contrast-enhancing HGG which have a tumor diameter no larger than 4cm or volume of 34cm3
• All patients must sign an informed consent indicating that they are aware of the investigational nature of this study.
• a. Patients must be\> 18 years old, and with a life expectancy \> 8 weeks
• Patients with Karnofsky performance status of \>= 70.
• At the time of registration: Patients must have recovered from the toxic effects of prior therapy: \> 10 days from any noncytotoxic investigational agent, \>28 days from prior cytotoxic therapy or Avastin, \>14 days from vincristine, \>42 days from nitrosoureas, \>21 days from procarbazine administration, and \>7 days for non-cytotoxic agents, e.g., interferon, tamoxifen, thalidomide, cis-retinoic acid, etc. (radiosensitizer does not count). Any questions related to the definition of non-cytotoxic agents should be directed to the Study Chair.
• Requirements for organ and marrow function as follows:
• Adequate bone marrow function:
• leukocytes \> 3,000/microliter (mcL)
• absolute neutrophil count \> 1,500/mcL

You may not qualify if:

• Patients must not have any significant medical illnesses that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy
• Patients with a history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission and off of all therapy for that disease for a minimum of 3 years are ineligible.
• HIV-positive patients on combination antiretroviral therapy are ineligible.
• Contrast-enhancing tumor which crosses the midline.
• Multi-focal disease.
• Nonparenchymal tumor dissemination (e.g., subependymal or leptomeningeal)
• History of hypersensitivity reactions to products containing irinotecan (irinotecan), topotecan or other topoisomerase inhibitors, gadolinium contrast agents or lipid products.
• Ongoing treatment with cytotoxic therapy.
• Patients may not be on an enzyme-inducing anti-epileptic drug (EIAED). If previously on an EIAED, patient must be off for at least 10 days prior to CED infusion.

Sponsors & Collaborators

• University of California, San Francisco: lead
• Ipsen: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

MeSH Terms

Conditions

Glioma

Interventions

irinotecan sucrosofate

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Officials

• Nicholas Butowski, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Neurological Surgery; Director of Clinical Services, Division of Neuro-Oncology

Study Record Dates

• First Submitted: December 11, 2013
• First Posted: December 30, 2013
• Study Start: October 23, 2014
• Primary Completion: December 31, 2020
• Study Completion: May 31, 2023
• Last Updated: June 29, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)