Clinical trial NCT03603379: Doxorubicin-loaded Anti-EGFR-immunoliposomes (C225-ILs-dox) in High-grade Gliomas
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Glioblastoma
Keywords: anti- EGFR- immunoliposomes
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
First posted: 2018-07-27
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Ratio of C225-ILs-dox concentration
timeFrame: 24 hours after first C225-ILs-dox application
Secondary outcomes:
measure: Tumour response according to RANO criteria on the final MRI scan
timeFrame: At the end of 4 treatment cycle 4 (each cycle is 28 days)
measure: Best achieved tumour response (1st or second MRI scan) during treatment phase according to RANO criteria (
timeFrame: between day 28 and day 104
measure: Event free survival
timeFrame: 12 months
measure: Progression free survival
timeFrame: 12 months
measure: Overall survival
timeFrame: 12 months
measure: Toxicity as graded by the CTCAE Version 4.0
timeFrame: 12 months
Other outcomes:
Locations:
city: Aarau
country: Switzerland
facility: Kantonsspital Aarau (KSA), Oncology
city: Basel
country: Switzerland
facility: Department of Oncology University Hospital Basel
Study officials:
affiliation: Dep. Oncology University Hospital Basel
name: Heinz Laeubli, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.