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

• ClinicalTrials.gov Identifier: NCT02833766
• Recruitment Status: Active, not recruiting
• First Posted: July 14, 2016
• Last Update Posted: April 24, 2020
• Sponsor: Swiss Group for Clinical Cancer Research
• Information provided by (Responsible Party): Swiss Group for Clinical Cancer Research

Study Description

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

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 48 participants
• Allocation: N/A
• 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
• Actual Study Start Date: October 28, 2016
• Estimated Primary Completion Date: December 2020
• Estimated Study Completion Date: December 2021

Arms and Interventions

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

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

• 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

Locations

Switzerland

Kantonsspital Aarau

Aarau, Switzerland, CH-5001

Kantonsspital Baden

Baden, Switzerland, CH-5404

Universitaetsspital-Basel

Basel, Switzerland, 4031

Inselspital, Bern

Bern, Switzerland, CH-3010

Kantonsspital Graubuenden

Chur, Switzerland, CH-7000

Hopitaux Universitaires de Geneve

Genève 14, Switzerland, 1211

Centre Hospitalier Universitaire Vaudois

Lausanne, Switzerland, CH-1011

Kantonsspital Luzern

Luzern, Switzerland, 6000

Kantonsspital Olten

Olten, Switzerland, 4600

Hôpital de Sion

Sion, Switzerland

Kantonsspital St. Gallen

St. Gallen, Switzerland, 9007

Spital STS AG

Thun, Switzerland, CH-3600

Kantonsspital Winterthur

Winterthur, Switzerland, 8401

Onkozentrum - Klinik im Park

Zurich, Switzerland, 8002

Universitätsspital Zürich

Zürich, Switzerland, 8091

Sponsors and Collaborators

Swiss Group for Clinical Cancer Research

Investigators

• Study Chair: Ralph Winterhalder, MD; Luzerner Kantonsspital

More Information

• Responsible Party: Swiss Group for Clinical Cancer Research
• ClinicalTrials.gov Identifier: NCT02833766
• Other Study ID Numbers: SAKK 24/14
• First Posted: July 14, 2016
• Last Update Posted: April 24, 2020
• Last Verified: April 2020

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; Antibiotics, Antineoplastic; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action