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

NCT03603379 | Completed Phase 1

• 1 other identifier: 2018-01160; me17Kasenda2
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Glioblastoma

Keywords

anti- EGFR- immunoliposomes

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Tumour response according to RANO criteria on the final MRI scan

  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 (

  between day 28 and day 104

• Event free survival

  12 months

• Progression free survival

  12 months

• Overall survival

  12 months

Study Arms (1)

C225-ILs-dox i.v.

EXPERIMENTAL

C225-ILs-dox administered intravenously

Drug: C225-ILs-dox

Interventions

C225-ILs-dox DRUG

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.

C225-ILs-dox i.v.

Eligibility Criteria

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

You may qualify if:

• Written informed consent according to International Conference on Harmonization (ICH)/Good Clinical Practice (GCP) regulations before registration and prior to any trial specific procedures
• Patients with relapsed histologically proven glioblastoma ≥ 18 years of age.
• Patients need to have at least one line of treatment with combined radio-chemotherapy
• 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.
• Evaluable disease on MRI brain scan
• Adequate bone marrow function: neutrophils ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L
• 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
• Adequate renal function: serum creatinine ≤ 1.5 x ULN and calculated creatinine clearance \> 30 mL/min, according to the formula of Cockcroft-Gault
• 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
• 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).
• No contraindications for lumbar puncture

You may not qualify if:

• 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.
• Lack to provide written informed consent
• Previous therapy with more than 240 mg/m2 of doxorubicin or more than 450 mg/m2 of epirubicin
• 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.)
• Breastfeeding and pregnancy
• Participation in any investigational drug trial within 4 weeks preceding treatment start
• Any concomitant drugs contraindicated when administering Erbitux™ or Caelyx™ according to the Swissmedic-approved product information
• Known hypersensitivity to trial drug(s) or to any component of the trial drug(s)
• 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.

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead

Study Sites (2)

Kantonsspital Aarau (KSA), Oncology

Aarau, 5001, Switzerland

Location

Department of Oncology University Hospital Basel

Basel, 4031, Switzerland

Location

Related Publications (1)

• 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.

  PMID: 34998092 DERIVED

MeSH Terms

Conditions

Glioblastoma

Condition Hierarchy (Ancestors)

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

Study Officials

• Heinz Laeubli, MD

  Dep. Oncology University Hospital Basel

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 17, 2018
• First Posted: July 27, 2018
• Study Start: November 16, 2018
• Primary Completion: November 1, 2020
• Study Completion: November 1, 2020
• Last Updated: December 8, 2020

Record last verified: 2020-12

Locations

CH (2)