## Protocol Section
### Identification Module
**NCT ID:** NCT03603379

**Acronym:** GBM-LIPO

**Brief Title:** 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

#### Organization Study ID Info
**ID:** 2018-01160; me17Kasenda2
#### Organization
**Class:** OTHER
**Full Name:** University Hospital, Basel, Switzerland
### Status Module
#### Completion Date
**Date:** 2020-11-01

**Type:** ACTUAL

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2020-12-08

**Type:** ACTUAL

**Last Update Submit Date:** 2020-12-07

**Overall Status:** COMPLETED

#### Primary Completion Date
**Date:** 2020-11-01

**Type:** ACTUAL

#### Start Date
**Date:** 2018-11-16

**Type:** ACTUAL

**Status Verified Date:** 2020-12

#### Study First Post Date
**Date:** 2018-07-27
**Type:** ACTUAL
**Study First Submit Date:** 2018-07-17
**Study First Submit QC Date:** 2018-07-26
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** University Hospital, Basel, Switzerland

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**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 Module

**Conditions:**

- Glioblastoma

**Keywords:**

- anti- EGFR- immunoliposomes

### Design Module

#### Design Info

**Allocation:** NA

**Intervention Model:** SINGLE_GROUP

##### Masking Info

**Masking:** NONE

**Primary Purpose:** BASIC_SCIENCE

#### Enrollment Info

**Count:** 9

**Type:** ACTUAL

**Phases:**

- PHASE1

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** C225-ILs-dox administered intravenously

**Intervention Names:**

- Drug: C225-ILs-dox

**Label:** C225-ILs-dox i.v.

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- C225-ILs-dox i.v.

**Description:** 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.

**Name:** C225-ILs-dox

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** Ratio of C225-ILs-dox concentration in cerebro-spinal fluid over the C225-ILs-dox concentration in peripheral blood.

**Measure:** Ratio of C225-ILs-dox concentration

**Time Frame:** 24 hours after first C225-ILs-dox application

#### Secondary Outcomes

**Description:** 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

**Measure:** Tumour response according to RANO criteria on the final MRI scan

**Time Frame:** At the end of 4 treatment cycle 4 (each cycle is 28 days)

**Description:** 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

**Measure:** Best achieved tumour response (1st or second MRI scan) during treatment phase according to RANO criteria (

**Time Frame:** between day 28 and day 104

**Description:** Defined as the time between registration to progression, termination of therapy for toxicity, or death whichever occurs first.

**Measure:** Event free survival

**Time Frame:** 12 months

**Description:** Defined as the time between registration to progression or death whichever occurs first

**Measure:** Progression free survival

**Time Frame:** 12 months

**Description:** Defined as the time between registration to death due to any cause

**Measure:** Overall survival

**Time Frame:** 12 months

**Description:** CTCAE grade 4 Life-threatening consequences; urgent intervention indicated; Neutrophils \< 0.5 x 109/l or Platelets \< 25 x 109/l; febrile neutropenia

**Measure:** Toxicity as graded by the CTCAE Version 4.0

**Time Frame:** 12 months

### Eligibility Module

**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 Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Aarau

**Country:** Switzerland

**Facility:** Kantonsspital Aarau (KSA), Oncology

**Zip:** 5001

**Location 2:**

**City:** Basel

**Country:** Switzerland

**Facility:** Department of Oncology University Hospital Basel

**Zip:** 4031

#### Overall Officials

**Official 1:**

**Affiliation:** Dep. Oncology University Hospital Basel

**Name:** Heinz Laeubli, MD

**Role:** PRINCIPAL_INVESTIGATOR

### References Module

#### 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.

**PMID:** 34998092

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000001254

- Term: Astrocytoma

- ID: D000005910

- Term: Glioma

- ID: D000018302

- Term: Neoplasms, Neuroepithelial

- ID: D000017599

- Term: Neuroectodermal Tumors

- ID: D000009373

- Term: Neoplasms, Germ Cell and Embryonal

- ID: D000009370

- Term: Neoplasms by Histologic Type

- ID: D000009369

- Term: Neoplasms

- ID: D000009375

- Term: Neoplasms, Glandular and Epithelial

- ID: D000009380

- Term: Neoplasms, Nerve Tissue

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: All

- Name: All Conditions

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M9020

- Name: Glioma

- Relevance: LOW

- As Found: Unknown

- ID: M9019

- Name: Glioblastoma

- Relevance: HIGH

- As Found: Glioblastoma

- ID: M4561

- Name: Astrocytoma

- Relevance: LOW

- As Found: Unknown

- ID: M20446

- Name: Neoplasms, Neuroepithelial

- Relevance: LOW

- As Found: Unknown

- ID: M19845

- Name: Neuroectodermal Tumors

- Relevance: LOW

- As Found: Unknown

- ID: M20388

- Name: Neuroectodermal Tumors, Primitive

- Relevance: LOW

- As Found: Unknown

- ID: M12318

- Name: Neoplasms, Germ Cell and Embryonal

- Relevance: LOW

- As Found: Unknown

- ID: M12315

- Name: Neoplasms by Histologic Type

- Relevance: LOW

- As Found: Unknown

- ID: M12320

- Name: Neoplasms, Glandular and Epithelial

- Relevance: LOW

- As Found: Unknown

- ID: M12325

- Name: Neoplasms, Nerve Tissue

- Relevance: LOW

- As Found: Unknown

- ID: T2519

- Name: Glioma

- Relevance: LOW

- As Found: Unknown

- ID: T2518

- Name: Glioblastoma

- Relevance: HIGH

- As Found: Glioblastoma

- ID: T4092

- Name: Neuroepithelioma

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000005909

- Term: Glioblastoma

### Intervention Browse Module - Browse Branches

- Abbrev: ANeo

- Name: Antineoplastic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M315

- Name: Cetuximab

- Relevance: LOW

- As Found: Unknown

- ID: M7492

- Name: Doxorubicin

- Relevance: LOW

- As Found: Unknown

- ID: M227339

- Name: Liposomal doxorubicin

- Relevance: LOW

- As Found: Unknown

- ID: M11900

- Name: Mitogens

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-24
