Anti-EGFR-immunoliposomes Loaded With Doxorubicin in Patients With Advanced Triple Negative EGFR Positive Breast Cancer

Breast Cancer Clinical Trial

Official title:

Anti-EGFR-immunoliposomes Loaded With Doxorubicin in Patients With Advanced Triple Negative EGFR Positive Breast Cancer - A Multicenter Single Arm Phase II Trial

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02833766
• Other study ID #: SAKK 24/14
• Status: Terminated
• Phase: Phase 2
• Start date: October 28, 2016
• Est. completion date: August 3, 2021

Study information

• Verified date: September 2021
• Source: Swiss Group for Clinical Cancer Research
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The main objective of the trial is to determine the efficacy of doxorubicin-loaded anti-EGFR immunoliposomes as first-line therapy in patients with advanced triple Negative, EGFR positive breast cancer. In this proof of concept trial, all patients will have an administration of the doxorubicin-loaded anti-EGFR immunoliposomes (anti-EGFR-IL-dox) every 28 days, until progression or unacceptable toxicity.

Description:

Advanced triple negative breast cancer (TNBC) is a highly chemosensitive disease displaying a dismal short-term prognosis with more than three quarters of patients in progression 12 months after the initiation of conventional chemotherapy. Approximately 2/3 of TNBC are expressing EGFR and breast cancer, including TNBC, is a disease highly sensitive to anthracyclines. Furthermore, data from a phase I trial, in 26 patients with different solid tumors, show very little toxicity and signs of efficacy of anti-EGFR-IL-dox.

The EGFR assessment will be performed centrally and only patients with EGFR positive tumors will be included. The patients will be treated with the anti-EGFR-IL-dox until progression and followed-up according to standard practice for patient with TNBC.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 48
• Est. completion date: August 3, 2021
• Est. primary completion date: October 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Written informed consent according to ICH/GCP regulations before prescreening and registration and prior to any trial specific procedures, including participation in mandatory translational research

• Histologically proven diagnosis of TNBC in metastatic or locally advanced non operable stage

• EGFR expression in primary tumor or metastases of at least (1+) in immunohistochemistry, assessed by central pathologist

• Measurable or evaluable disease according to RECIST 1.1

• No prior systemic treatment for metastatic or inoperable disease

• Adequate bone marrow function: neutrophils = 1.5 x 109/L, platelets = 100 x 109/L

• Adequate hepatic function: total bilirubin = 1.5 x ULN; AST, ALT and AP = 2.5 x ULN (AST, ALT and AP = 5 x ULN if hepatic metastases are the only reason for enzyme elevation)

• 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) = 40% as determined by either echocardiography (ECHO) or radionuclide angiocardiography (MUGA)

Exclusion Criteria:

• Evidence of CNS or leptomeningeal metastases (even if previously treated); CNS imaging not required in asymptomatic patients

• History of hematologic or primary solid tumor malignancy, unless in remission for at least 5 years from registration. Inclusion of adequately treated cervical carcinoma in situ or localized non-melanoma skin cancer is permitted independent of time since diagnosis

• Previous therapy with more than 240 mg/m2 of doxorubicin or more than 450 mg/m2 of epirubicin

• Previous radiotherapy for the metastatic disease (palliative radiotherapy of only non-target lesions is allowed)

• Adjuvant treatment must have been stopped at least 6 months before registration

• 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

• 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.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• anti-EGFR-IL-dox
First-line treatment with anti-EGFR-IL-dox, given at a dose of 50 mg/m2 intravenous, on day 1 of each cycle, cycle length is 28 days

Locations

Country	Name	City	State
Switzerland	Kantonsspital Aarau	Aarau
Switzerland	Kantonsspital Baden	Baden
Switzerland	Universitaetsspital-Basel	Basel
Switzerland	Inselspital, Bern	Bern
Switzerland	Kantonsspital Graubuenden	Chur
Switzerland	Hopitaux Universitaires de Geneve	Genève 14
Switzerland	Centre Hospitalier Universitaire Vaudois	Lausanne
Switzerland	Kantonsspital Luzern	Luzern
Switzerland	Kantonsspital Olten	Olten
Switzerland	Hôpital de Sion	Sion
Switzerland	Kantonsspital St. Gallen	St. Gallen
Switzerland	Spital STS AG	Thun
Switzerland	Kantonsspital Winterthur	Winterthur
Switzerland	Onkozentrum - Klinik im Park	Zurich
Switzerland	Universitätsspital Zürich	Zürich

Sponsors (1)

Lead Sponsor	Collaborator
Swiss Group for Clinical Cancer Research

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival (PFS)	PFS is defined as the time from registration until progression according to RECIST v1.1 or death from any cause, whichever occurs first.	at 12 months after registration
Secondary	Objective response rate (ORR)	ORR is defined as proportion of patients achieving complete response (CR) or partial response (PR) according to RECIST v1.1 during trial treatment.	at 12 months after registration
Secondary	Duration of response (DOR)	DOR is defined as time from the date when a patient first meets the criteria for CR or PR according to RECIST v1.1, until documented progression, relapse or death due to disease progression, whichever occurs first.	at 12 months after registration
Secondary	Time to Progression (TTP)	Time to Progression (TTP), defined as the time from registration until progression TTP assessed according to RECIST v1.1 or death due to disease progression, whichever occurs first.	at 12 months after registration
Secondary	PFS	PFS is defined as the time from registration until progression according to RECIST v1.1 or death from any cause, whichever occurs first.	at 12 months after registration
Secondary	Overall survival (OS)	OS is defined as time from registration until death from any cause.	at 12 months after registration
Secondary	Adverse events (AEs)	AE are assessed according to NCI CTCAE v4.0.	at 12 months after registration