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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: anti-EGFR-IL-dox


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: anti-EGFR-IL-dox<br>Metastatic, non resectable, EGFR positive TNBC patients treated in first-line | Drug: anti-EGFR-IL-dox<br>* 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<br>* Other names: anti-EGFR-immunoliposomes loaded with doxorubicin;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast Cancer, advanced triple Negative, EGFR positive breast cancer, doxorubicin, triple negative breast cancer (TNBC)