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A Phase I Study of Doxorubicin-loaded Anti-EGFR Immunoliposomes in Patients With Advanced Solid Tumors
Sponsor study identifier
interventional
26
1 country
1
Study Start
January 2007
Date type not reportedThis date has not been verified as actual or estimated.
Primary Completion
March 2010
Actual (reported)Study Completion
March 2010
Actual (reported)Background: Site-specific delivery of anti-cancer therapeutics is paramount for both reducing nonspecific toxicities and increasing efficacy of chemotherapeutic agents. Due to their small molecular size and nonspecific mechanisms of action, most conventional chemotherapies result in significant toxicities that limit the effectiveness of treatment and reduce the overall quality of life for cancer patients. Encapsulation of these toxic agents inside lipid-based carrier systems (so-called liposomes) results in passive targeting of the compounds to solid tumors. The preferential delivery of liposomal drugs to solid tumors is mostly due to altered barrier-properties of tumor-associated vessels. This results in both an improved delivery and at the same time a significantly milder toxicity profile. Recently, the specificity of delivery was further increased by attaching monoclonal antibodies or antibody fragments to the surface of liposomes (=immunoliposomes, antibody-linked nanoparticles). Antibody-coated immunoliposomes attach more selectively to antigens expressed on the target cells and they are internalized more efficiently. Furthermore, there is evidence that drug resistance, a major challenge in cancer treatment, may be overcome by such delivery systems. A logical and accessible target, such as EGFR, is overexpressed on a variety of primary human cancer cells and it is involved in signaling pathways that contribute both to tumor initiation and tumor progression. Recently, the investigators have tested immunoliposomes against the epidermal growth factor receptor (EGFR) in a preclinical setting. Based on the preclinical results we have initiated this phase I clinical trial. Study hypothesis: The investigators hypothesize that anti-EGFR-immunoliposomes selectively deliver cytotoxic compounds to EGFR-overexpressing tumors cells. Specific delivery is supposed to increase efficacy while reducing side-effects of the compound. The primary objective of this phase 1 trial is the determination of the maximum tolerated dose (MTD) for future phase 2 trials of this nanoparticle.
Registry-reported information. Elapsed time and enrollment totals alone do not measure study progress or recruitment pace.
March 2010
Actual (reported)Click on a node to explore related trials.
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Dates and qualifiers reported by the registry. Estimated dates do not confirm that a milestone has occurred.
January 2007
Date type not reportedThis date has not been verified as actual or estimated.
March 2010
Actual (reported)March 2010
Actual (reported)October 1, 2012
Actual (reported)October 5, 2012
Actual (reported)Determination of the maximum tolerated dose (MTD)
The MTD is defined through the occurrence of two dose limiting toxicities (DLTs) at a specific dose level. DLT are defined as any grade 4 toxicity, any grade 3 toxicity lasting more than one week or/and febrile neutropenia grade 3 (defined as neutrophils \< 1.0 x 10e9/l and fever \> 38.5 °C). Nausea, vomiting, anorexia, and alopecia (grade 2) will be excluded as dose limiting toxicities. Similarly, adverse events that are clearly related to the primary tumor, such as progression of disease will not be considered as DLTs.
after completion of the 1st cycle (day 28)
CT scans for efficacy
every 2 months for 6 months and then every 3 months for a total of one year
anti-EGFR immunoliposomes loaded with doxorubicin. Dose escalating study. 3 patients per dose level. Dose levels: 5, 10, 20, 30, 40, 50 and 60 mg doxorubicin/m2.
All patients were treated with anti-EGFR immunoliposomes Different dose levels (5, 10, 20, 30, 40, 50 and 60 mg doxorubicin/m2), at least 3 patients per dose level, treatment was given every 4 weeks
Registry-reported names are shown in full. Names without a link have not yet been matched to a Syfrah profile.
University Hospital
Basel, Basel, 4031, Switzerland
Mamot C, Drummond DC, Greiser U, Hong K, Kirpotin DB, Marks JD, Park JW. Epidermal growth factor receptor (EGFR)-targeted immunoliposomes mediate specific and efficient drug delivery to EGFR- and EGFRvIII-overexpressing tumor cells. Cancer Res. 2003 Jun 15;63(12):3154-61.
Mamot C, Drummond DC, Noble CO, Kallab V, Guo Z, Hong K, Kirpotin DB, Park JW. Epidermal growth factor receptor-targeted immunoliposomes significantly enhance the efficacy of multiple anticancer drugs in vivo. Cancer Res. 2005 Dec 15;65(24):11631-8. doi: 10.1158/0008-5472.CAN-05-1093.
Christoph Mamot, MD
Cantonal Hospital of Aarau, Switzerland
26 participants (actual enrollment reported by the registry).
First Submitted
October 1, 2012
First Posted
October 5, 2012
Study Start
January 2007
Date type not reportedThis date has not been verified as actual or estimated.
Contact the study team to confirm eligibility.
Mamot C, Ritschard R, Wicki A, Stehle G, Dieterle T, Bubendorf L, Hilker C, Deuster S, Herrmann R, Rochlitz C. Tolerability, safety, pharmacokinetics, and efficacy of doxorubicin-loaded anti-EGFR immunoliposomes in advanced solid tumours: a phase 1 dose-escalation study. Lancet Oncol. 2012 Dec;13(12):1234-41. doi: 10.1016/S1470-2045(12)70476-X. Epub 2012 Nov 13.
Primary Completion
March 2010
Actual (reported)Study Completion
March 2010
Actual (reported)Last Updated
September 9, 2014
Record last verified: 2014-09
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Source: ClinicalTrials.gov.
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