Doxorubicin-loaded Anti-EGFR-immunoliposomes (C225-ILs-dox) in High-grade Gliomas (GBM-LIPO)

A Pharmacokinetic Phase 1 Study of Anti-epidermal Growth Factor Receptor (EGFR) -Immunoliposomes Loaded With Doxorubicin in Patients With Relapsed or Refractory High-grade Gliomas

Anti-EGFR-immunoliposomes loaded with doxorubicin (C225-ILs-dox) are given intravenously in patients with relapsed or refractory high-grade gliomas.

The pharmacokinetics of C225-ILs-dox in peripheral blood (PB), cerebro-spinal fluid (CSF) and resected tumour tissue will be assessed.

Study Overview

• Status: Completed
• Conditions: Glioblastoma
• Intervention / Treatment: Drug: C225-ILs-dox

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 1

Contacts and Locations

Study Locations

• Switzerland
  • Aarau, Switzerland, 5001
    • Kantonsspital Aarau (KSA), Oncology
  • Basel, Switzerland, 4031
    • Department of Oncology University Hospital Basel

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Written informed consent according to International Conference on Harmonization (ICH)/Good Clinical Practice (GCP) regulations before registration and prior to any trial specific procedures
2. Patients with relapsed histologically proven glioblastoma ≥ 18 years of age.
3. Patients need to have at least one line of treatment with combined radio-chemotherapy
4. EGFR amplification. EGFR amplification will be tested by comparative genomic hybridization (CGH) method. EGFR will be considered amplified if the value is 0.15 above the average signal of chromosome 7.
5. Evaluable disease on MRI brain scan
6. Adequate bone marrow function: neutrophils ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L
7. Adequate hepatic function: bilirubin ≤ 1.5 x upper limit of normal (ULN), aspartate aminotransferase (AST), Alanin-Aminotransferase (ALT) and alkaline phosphatase (AP) ≤ 2.5 x ULN
8. Adequate renal function: serum creatinine ≤ 1.5 x ULN and calculated creatinine clearance > 30 mL/min, according to the formula of Cockcroft-Gault
9. Adequate cardiac function: Left ventricular Ejection Fraction (LVEF) ≥ 50% as determined by either echocardiography (ECHO) or radionuclide angiocardiography (MUGA) in addition to pre- (brain-type natriuretic Peptide) BNP from peripheral blood
10. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 (0=Fully active, able to carry on all pre-disease performance without restriction, 1=Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work, 2=Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours).
11. No contraindications for lumbar puncture
12. Women with child-bearing potential have to use effective contraception, are not allowed to be pregnant and have to agree not to become pregnant during trial treatment and during the 6 months thereafter. A negative pregnancy test before inclusion into the trial is required for all women with child-bearing potential.

Exclusion Criteria:

1. History of hematologic or primary solid tumor malignancy, unless in remission for at least 3 years from registration except for adequately treated cervical carcinoma in situ and localized non-melanoma skin cancer.
2. Lack to provide written informed consent
3. Previous therapy with more than 240 mg/m2 of doxorubicin or more than 450 mg/m2 of epirubicin
4. Any serious underlying medical condition (at the judgement of the investigator) which could impair the ability of the patient to participate in the trial (e.g. active autoimmune disease, uncontrolled diabetes, etc.)
5. Breastfeeding and pregnancy
6. Participation in any investigational drug trial within 4 weeks preceding treatment start
7. Any concomitant drugs contraindicated when administering Erbitux™ or Caelyx™ according to the Swissmedic-approved product information
8. Known hypersensitivity to trial drug(s) or to any component of the trial drug(s)
9. Any other serious underlying medical, psychiatric, psychological, familial or geographical condition, which in the judgment of the investigator may interfere with the planned staging, treatment and follow-up, affect patient compliance or place the patient at high risk from treatment-related complications.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: C225-ILs-dox i.v.; C225-ILs-dox administered intravenously	Drug: C225-ILs-dox; C225-ILs-dox will be administered at a dose of 50 mg/m2. i.v., on day 1 of each cycle, cycle length is 28 days. In total, 4 cycles are planned to be applied.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ratio of C225-ILs-dox concentration	Ratio of C225-ILs-dox concentration in cerebro-spinal fluid over the C225-ILs-dox concentration in peripheral blood.	24 hours after first C225-ILs-dox application

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumour response according to RANO criteria on the final MRI scan	Tumour response according to RANO criteria; RANO criteria: divides response into four types of response based on imaging (MRI) and clinical features: complete response partial response stable disease progression	At the end of 4 treatment cycle 4 (each cycle is 28 days)
Best achieved tumour response (1st or second MRI scan) during treatment phase according to RANO criteria (	1st or second MRI scan during treatment phase according to RANO criteria. RANO criteria: divides response into four types of response based on imaging (MRI) and clinical features: complete response partial response stable disease progression	between day 28 and day 104
Event free survival	Defined as the time between registration to progression, termination of therapy for toxicity, or death whichever occurs first.	12 months
Progression free survival	Defined as the time between registration to progression or death whichever occurs first	12 months
Overall survival	Defined as the time between registration to death due to any cause	12 months
Toxicity as graded by the CTCAE Version 4.0	CTCAE grade 4 Life-threatening consequences; urgent intervention indicated; Neutrophils < 0.5 x 109/l or Platelets < 25 x 109/l; febrile neutropenia	12 months

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland
• Investigators: Principal Investigator: Heinz Laeubli, MD, Dep. Oncology University Hospital Basel

Publications and helpful links

General Publications

• Kasenda B, Konig D, Manni M, Ritschard R, Duthaler U, Bartoszek E, Barenwaldt A, Deuster S, Hutter G, Cordier D, Mariani L, Hench J, Frank S, Krahenbuhl S, Zippelius A, Rochlitz C, Mamot C, Wicki A, Laubli H. Targeting immunoliposomes to EGFR-positive glioblastoma. ESMO Open. 2022 Feb;7(1):100365. doi: 10.1016/j.esmoop.2021.100365. Epub 2022 Jan 5.

Study record dates

Study Major Dates

• Study Start (Actual): November 16, 2018
• Primary Completion (Actual): November 1, 2020
• Study Completion (Actual): November 1, 2020

Study Registration Dates

• First Submitted: July 17, 2018
• First Submitted That Met QC Criteria: July 26, 2018
• First Posted (Actual): July 27, 2018

Study Record Updates

• Last Update Posted (Actual): December 8, 2020
• Last Update Submitted That Met QC Criteria: December 7, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: anti- EGFR- immunoliposomes
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma
• Other Study ID Numbers: 2018-01160; me17Kasenda2

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No