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

Study Description

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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.

Condition or disease	Intervention/treatment	Phase
Breast Cancer	Drug: anti-EGFR-IL-dox	Phase 2

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 Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	49 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
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 Start Date :	October 2016
Estimated Primary Completion Date :	June 2019
Estimated Study Completion Date :	December 2021

Arms and Interventions

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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 Name: anti-EGFR-immunoliposomes loaded with doxorubicin

Outcome Measures

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Primary Outcome Measures :

1. Progression-free survival (PFS) [ Time Frame: at 12 months after registration ]
   PFS is defined as the time from registration until progression according to RECIST v1.1 or death from any cause, whichever occurs first.

Secondary Outcome Measures :

1. Objective response rate (ORR) [ Time Frame: at 12 months after registration ]
   ORR is defined as proportion of patients achieving complete response (CR) or partial response (PR) according to RECIST v1.1 during trial treatment.
2. Duration of response (DOR) [ Time Frame: at 12 months after registration ]
   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.
3. Time to Progression (TTP) [ Time Frame: at 12 months after registration ]
   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.
4. PFS [ Time Frame: at 12 months after registration ]
   PFS is defined as the time from registration until progression according to RECIST v1.1 or death from any cause, whichever occurs first.
5. Overall survival (OS) [ Time Frame: at 12 months after registration ]
   OS is defined as time from registration until death from any cause.
6. Adverse events (AEs) [ Time Frame: at 12 months after registration ]
   AE are assessed according to NCI CTCAE v4.0.

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

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Contacts

Contact: Martina Schneider	+41 31 389 91 91	trials@sakk.ch

Locations

Switzerland
Kantonsspital Aarau	Recruiting
Aarau, Switzerland, CH-5001
Contact: Christoph Mamot, MD +41 62 838 60 64 christoph.mamot@ksa.ch
Principal Investigator: Christoph Mamot, MD
Kantonsspital Baden	Recruiting
Baden, Switzerland, CH-5404
Contact: Clemens B. Caspar, MD 41-56-486-2762 clemens.caspar@ksb.ch
Principal Investigator: Clemens Caspar, MD
Universitaetsspital-Basel	Recruiting
Basel, Switzerland, 4031
Contact: Christoph Rochlitz, Prof +41 61 265 50 74 crochlitz@uhbs.ch
Principal Investigator: Christoph Rochlitz, Prof
St. Claraspital	Recruiting
Basel, Switzerland, CH-4016
Contact: Corinne Cescato, MD +41 61 685 84 39 corinne.cescato@claraspital.ch
Principal Investigator: Corinne Cescato, MD
Inselspital, Bern	Recruiting
Bern, Switzerland, CH-3010
Contact: Urban Novak, MD +41 31 632 19 92 urban.novak@insel.ch
Principal Investigator: Urban Novak, MD
Hopitaux Universitaires de Geneve	Recruiting
Genève 14, Switzerland, 1211
Contact: Alexandre Bodmer, MD +41 22 372 40 14 alexandre.bodmer@hcuge.ch
Principal Investigator: Alexandre Bodmer, MD
Centre Hospitalier Universitaire Vaudois	Recruiting
Lausanne, Switzerland, CH-1011
Contact: Khalil Zaman, MD 41-21-314-4658 khalil.zaman@chuv.ch
Principal Investigator: Khalil Zaman, MD
Kantonsspital Luzern	Recruiting
Luzern, Switzerland, 6000
Contact: Ralph Winterhalder, MD +41 41 205 58 75 ralph.winterhalder@ksl.ch
Principal Investigator: Ralph Winterhalder, MD
Kantonsspital Olten	Recruiting
Olten, Switzerland, 4600
Contact: Catrina Uhlmann Nussbaum, MD +41 62 311 42 41 cuhlmann_ol@spital.ktso.ch
Principal Investigator: Catrina Uhlmann Nussbaum, MD
Hôpital de Sion	Recruiting
Sion, Switzerland
Contact: Véronique Membrez, MD +41 27 603 48 53 veronique.membrez@hopitalvs.ch
Principal Investigator: Véronique Membrez, MD
Kantonsspital St. Gallen	Recruiting
St. Gallen, Switzerland, 9007
Contact: Ursula Hasler-Strub, MD +41 71 494 19 32 ursula.hasler-strub@kssg.ch
Principal Investigator: Ursula Hasler-Strub, MD
Spital STS AG	Recruiting
Thun, Switzerland, CH-3600
Contact: Daniel Rauch, MD +41 33 226 26 45 daniel.rauch@spitalstsag.ch
Principal Investigator: Daniel Rauch, MD
Onkozentrum - Klinik im Park	Recruiting
Zurich, Switzerland, 8002
Contact: Andreas Trojan, MD +41 43 344 33 33 trojan@ist.ch
Principal Investigator: Andreas Trojan, MD
Universitätsspital Zürich	Recruiting
Zürich, Switzerland, 8091
Contact: Konstantin Dedes, MD +41 44 255 1613 Konstantin.dedes@usz.ch
Principal Investigator: Konstantin Dedes, MD

Sponsors and Collaborators

Swiss Group for Clinical Cancer Research

Investigators

Study Chair:	Ralph Winterhalder, MD	Luzerner Kantonsspital

More Information

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Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Swiss Group for Clinical Cancer Research
ClinicalTrials.gov Identifier:	NCT02833766 History of Changes
Other Study ID Numbers:	SAKK 24/14
First Posted:	July 14, 2016
Last Update Posted:	November 1, 2017
Last Verified:	October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

Keywords provided by Swiss Group for Clinical Cancer Research:

Breast Cancer; advanced triple Negative, EGFR positive breast cancer; doxorubicin; triple negative breast cancer (TNBC)

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Doxorubicin; Liposomal doxorubicin	Antibiotics, Antineoplastic; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action