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

NCT ID: NCT03603379

Last Updated: 2020-12-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 9 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-11-16
• Study Completion Date: 2020-11-01

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

C225-ILs-dox i.v.

C225-ILs-dox administered intravenously

Group Type: EXPERIMENTAL

C225-ILs-dox

Intervention Type: 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.

Interventions

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.

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Basel, Switzerland

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Heinz Laeubli, MD

Role: PRINCIPAL_INVESTIGATOR

Dep. Oncology University Hospital Basel

Locations

Kantonsspital Aarau (KSA), Oncology

Aarau, , Switzerland

Department of Oncology University Hospital Basel

Basel, , Switzerland

Countries

Switzerland

References

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.

Reference Type: DERIVED

PMID: 34998092 (View on PubMed)

Other Identifiers

2018-01160; me17Kasenda2

Identifier Type: -

Identifier Source: org_study_id