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

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

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.

Study Overview

• Status: Terminated
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: anti-EGFR-IL-dox

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 2

Contacts and Locations

Study Locations

• Switzerland
  • Aarau, Switzerland, CH-5001
    • Kantonsspital Aarau
  • Baden, Switzerland, CH-5404
    • Kantonsspital Baden
  • Basel, Switzerland, 4031
    • Universitaetsspital-Basel
  • Bern, Switzerland, CH-3010
    • Inselspital, Bern
  • Chur, Switzerland, CH-7000
    • Kantonsspital Graubuenden
  • Genève 14, Switzerland, 1211
    • Hopitaux Universitaires de Geneve
  • Lausanne, Switzerland, CH-1011
    • Centre Hospitalier Universitaire Vaudois
  • Luzern, Switzerland, 6000
    • Kantonsspital Luzern
  • Olten, Switzerland, 4600
    • Kantonsspital Olten
  • Sion, Switzerland
    • Hopital de Sion
  • St. Gallen, Switzerland, 9007
    • Kantonsspital St. Gallen
  • Thun, Switzerland, CH-3600
    • Spital STS AG
  • Winterthur, Switzerland, 8401
    • Kantonsspital Winterthur
  • Zurich, Switzerland, 8002
    • Onkozentrum - Klinik im Park
  • Zürich, Switzerland, 8091
    • Universitatsspital Zurich

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: anti-EGFR-IL-dox; Metastatic, non resectable, EGFR positive TNBC patients treated in first-line	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; Other Names: anti-EGFR-immunoliposomes loaded with doxorubicin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
Overall survival (OS)	OS is defined as time from registration until death from any cause.	at 12 months after registration
Adverse events (AEs)	AE are assessed according to NCI CTCAE v4.0.	at 12 months after registration

Collaborators and Investigators

• Sponsor: Swiss Group for Clinical Cancer Research
• Investigators: Study Chair: Ralph Winterhalder, MD, Luzerner Kantonsspital

Study record dates

Study Major Dates

• Study Start (Actual): October 28, 2016
• Primary Completion (Actual): October 31, 2020
• Study Completion (Actual): August 3, 2021

Study Registration Dates

• First Submitted: July 12, 2016
• First Submitted That Met QC Criteria: July 13, 2016
• First Posted (Estimate): July 14, 2016

Study Record Updates

• Last Update Posted (Actual): September 29, 2021
• Last Update Submitted That Met QC Criteria: September 27, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: Breast Cancer; triple negative breast cancer (TNBC); doxorubicin; advanced triple Negative, EGFR positive breast cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Doxorubicin
• Other Study ID Numbers: SAKK 24/14

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO