Oxford BioMedica announced that the first stage of its Phase II trial in pancreatic cancer with MetXia, the company's gene targeted prodrug activation product, has been successfully completed
The objectives were to assess the safety of administering MetXia locally to the pancreatic tumour, to confirm gene transfer at the tumour site following local delivery and to identify an optimal dose for the second stage of the trial.
The two-stage Phase II trial is designed to evaluate MetXia and the chemotherapy prodrug cyclosphosphamide (CPA) in patients undergoing palliative surgery for pancreatic cancer.
The trial is being conducted at the Royal Liverpool University Hospital.
In the first stage of the trial, two dose levels of MetXia were assessed in six patients in combination with a low dose of CPA.
Each patient had two administrations of MetXia, prior and subsequent to surgery, followed by CPA.
Both dose levels of MetXia were safe and well tolerated.
Importantly, dose dependent expression of the specific human cytochrome P450 gene, delivered by MetXia, was observed in tumour biopsies taken at surgery.
MetXia comprises a highly engineered retrovirus that delivers the P450 gene to tumour cells.
The enzyme encoded by the P450 gene activates CPA to a form that destroys cells.
With conventional oral and intravenous administration of CPA, the drug is activated in the liver by the P450 enzyme.
This trial utilises catheter-enabled local delivery of both MetXia and CPA to the pancreas, thereby focusing gene delivery and activation of CPA in the target tissue.
This minimises the side effects of liver toxicity and systemic dispersal of activated CPA that are associated with oral administration of CPA.
The route of administration represents a novel and potentially highly potent strategy for optimising chemotherapy at the tumour site.
Following the encouraging results in stage one of the trial, patient recruitment is commencing for the second stage with a fixed dose of MetXia and increasing doses of CPA.
Stage two will accrue up to 25 patients and will determine the optimal dose of CPA.
This second stage of the trial is designed to evaluate clinical benefit as well as safety.
An additional clinical trial site in London is expected to open for part two of the trial, which will boost patient accrual.
Preliminary efficacy data is expected in early 2006.
Commenting on the MetXia results, Oxford BioMedica's chief executive, professor Alan Kingsman said: "It is very encouraging that MetXia has achieved its endpoints of safety and gene transfer with this novel route of delivery".
"We look forward to evaluating clinical benefit in the next stage of the trial".
"There is a clear unmet need for effective therapies for pancreatic cancer, which MetXia has the potential to address."
