Clinical trial NCT02833766: Anti-EGFR-immunoliposomes Loaded With Doxorubicin in Patients With Advanced Triple Negative EGFR Positive Breast Cancer
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: Breast Cancer
advanced triple Negative, EGFR positive breast cancer
doxorubicin
triple negative breast cancer (TNBC)
Lead sponsor: Swiss Group for Clinical Cancer Research
Sponsor class: OTHER
First posted: 2016-07-14
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Progression-free survival (PFS)
timeFrame: at 12 months after registration
Secondary outcomes:
measure: Objective response rate (ORR)
timeFrame: at 12 months after registration
measure: Duration of response (DOR)
timeFrame: at 12 months after registration
measure: Time to Progression (TTP)
timeFrame: at 12 months after registration
measure: PFS
timeFrame: at 12 months after registration
measure: Overall survival (OS)
timeFrame: at 12 months after registration
measure: Adverse events (AEs)
timeFrame: at 12 months after registration
Other outcomes:
Locations:
city: Aarau
country: Switzerland
facility: Kantonsspital Aarau
city: Baden
country: Switzerland
facility: Kantonsspital Baden
city: Basel
country: Switzerland
facility: Universitaetsspital-Basel
city: Bern
country: Switzerland
facility: Inselspital, Bern
city: Chur
country: Switzerland
facility: Kantonsspital Graubuenden
city: Genève 14
country: Switzerland
facility: Hopitaux Universitaires de Geneve
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois
city: Luzern
country: Switzerland
facility: Kantonsspital Luzern
city: Olten
country: Switzerland
facility: Kantonsspital Olten
city: Sion
country: Switzerland
facility: Hôpital de Sion
city: St. Gallen
country: Switzerland
facility: Kantonsspital St. Gallen
city: Thun
country: Switzerland
facility: Spital STS AG
city: Winterthur
country: Switzerland
facility: Kantonsspital Winterthur
city: Zurich
country: Switzerland
facility: Onkozentrum - Klinik im Park
city: Zürich
country: Switzerland
facility: Universitätsspital Zürich
Study officials:
affiliation: Luzerner Kantonsspital
name: Ralph Winterhalder, MD
role: STUDY_CHAIR
References: