Starpharma has received approvals to commence a phase I human clinical trial for its dendrimer-enhanced docetaxel (Taxotere) chemotherapeutic product, referred to as DEP-Docetaxel.
The trial will be conducted exclusively in Australia, at Nucleus Network's clinical facility at the AMREP/Alfred Hospital initially, with the plan to add one to two additional sites in the near future. The study will enrol approximately thirty patients with solid tumours. The primary objective of the study is to establish the maximum tolerated dose (MTD) and dose limiting toxicities (DLT) of DEP-Docetaxel, a new formulation of the major chemotherapeutic agent, docetaxel, which is marketed worldwide under the tradename, Taxotere. The study will also include a preliminary assessment of the anti-cancer efficacy of DEP-Docetaxel.
Earlier preclinical studies of Starpharma’s DEP-Docetaxel demonstrated the significantly superior anti-cancer effectiveness of the product compared to Taxotere across a range of important cancer types including breast, prostate, lung and ovarian cancer. In addition, DEP-Docetaxel exhibited a lack of the severe toxicity, neutropenia, which is the most important dose-limiting side effect of Taxotere. Use of Starpharma’s DEP technology also improved the water solubility and tissue targeting of docetaxel. This improvement means that unlike other marketed formulations of docetaxel, Starpharma’s DEP-Docetaxel is detergent (Polysorbate 80) free, delivering a number of potential patient tolerability and safety advantages compared to other formulations.
Starpharma chief executive, Dr Jackie Fairley said, “The commencement of this clinical trial of DEP-Docetaxel represents a key development milestone for this product and follows very strong preclinical results, which have included both improved efficacy and the reduction in important dose limiting side effects.”
“The multiple, clinically significant benefits of Starpharma’s DEP-Docetaxel will place the product in a very compelling competitive position. In addition, findings from this trial have potential flow-on benefit for Starpharma’s dendrimer platform more broadly, particularly in oncology,” said Dr Fairley.
DEP-Docetaxel is the first clinical candidate using Starpharma’s dendrimer based DEP technology. The features of these products allow them to access a streamlined development pathway compared to a completely novel product.
The primary objective of the clinical study is to establish the maximum tolerated dose (MTD) and dose limiting toxicities (DLT) of DEP-Docetaxel given intravenously (IV), once every three weeks. The secondary objective is to identify the safety, pharmacokinetic and tolerability profile of DEP-Docetaxel in patients with advanced cancer. Key outcomes of the study will be to define a recommended dose for future studies as well as to explore preliminary anti-tumour efficacy of the product.
Importantly, the study will also allow investigation of the impact of the improved dendrimer formulation on problematic side effects seen with Taxotere, such as neutropenia, which was markedly reduced with the dendrimer formulation in preclinical studies, anaphylaxis and hair loss. The study will also employ a variety of imaging techniques and specific investigations aimed at exploring anti-tumour efficacy. These include CT scans and bone scans, as well as tumour markers.
Consultant Oncologist, Dr Jason Lickliter, MBBS, PhD, FRACP, director, phase I Cancer Trials Programme, Southern Health and Monash Institute of Medical Research, and Medical Director, Nucleus Network, has been appointed as the study Principal Investigator.
Starpharma’s dendrimer-based drug delivery DEP technology has been utilised to reformulate and improve a number of marketed cancer drugs including docetaxel (Taxotere), oxaliplatin (Eloxatin) and doxorubicin. Preclinical studies of the dendrimer-enhanced versions have shown these reformulated DEP versions of the drugs to be superior to the commercially available formulation, often in multiple ways including improved efficacy, reduced toxicity and lower side effects. Starpharma also has several partnered programmes with leading pharma companies, including in oncology.
Expenditure on this trial will be eligible for the 45 per cent refundable R&D tax incentive. Docetaxel is a leading chemotherapy drug used to treat a wide range of solid tumours including breast, lung and prostate. It is marketed by Sanofi Aventis as Taxotere and generated sales in excess of US$ 3 billion in 2010.