Success Stories
Innovation and quality - trials in the Network
The ECMC Network and the people within it are central to the delivery of innovative research . These are just a sample of trials and studies supported by the initiative that are demonstrating hallmarks of quality.
Early phase cancer trials are unique, in that these studies tend to take place in patients, not in healthy volunteers. The expertise that resides in the network ensures that trials putting new treatment agents into patients for the first time can be done safely and ethically. The following are just a few examples of these studies.
Newcastle ECMC has opened a first in class Phase I trial, using a sphingomyelin synthase (SMS) activator. SMS is a novel anti-tumour target, and activation is thought to induce tumour cell death by increasing cellular levels of ceramide and diacylglycerol. This study is being conducted in collaboration with ICR/Marsden ECMC, and will also involve intensive PK and PD sampling.
Southampton continues to demonstrate their expertise in immunotherapy and have opened a DDO sponsored first in man Phase I study of a novel CD19 antibody for B cell disease. This study will recruit in four ECMC locations and will involve study of multiple surrogate tumour biomarkers.
Combining therapies has become an increasingly important strategy for combating cancer. The network is now supporting a substantial and varied portfolio of combination studies. The ECMC Combinations Alliance has been a key driver in this.
Belfast ECMC is leading on the pan European MErCuRIC project involving 13 partners from eight different European countries. MErCuRIC is a multicentre phase Ib/II clinical trial which will assess combination a MEK inhibitor (PD-0325901) with a MET inhibitor (PF-02341066) to combat metastasis, improve survival and change current clinical practice for colorectal cancer patients with KRAS mutant & wild type tumours. The consortium will use next generation sequencing and ‘xenopatients’ to identify patient subgroups that will maximally benefit from this novel treatment strategy. The study has been submitted for ethical and regulatory review.
Kings ECMC is leading on a Novartis trial combining docetaxel with a pan PI3 Kinase inhibitor, buparlisip in patients with advanced non-small cell lung cancer. This is an international trial with recruitment taking place at 56 sites.
As well as providing the infrastructure to support hundreds of drug development studies, the ECMC network hosts trials investigating novel and unusual therapeutics.
The ICR/Marsden ECMC completed a Phase I trial in patients with castration-resistant prostate cancer, using an antisense oligonucleotide to androgen receptor mRNA. This study demonstrated that the activity of the agent was minimal at the doses and schedules explored and was also associated with liver toxicity.
Leicester ECMC are supporting a trial examining if addition of the plant extract curcumin to the FOLFOX chemotherapy regimen for metastatic colorectal cancer improves efficacy or reduces sides effects. This work progresses from Phase I to randomised Phase II in year and is currently recruiting patients.
Birmingham ECMC has opened the AdUP trial to recruitment, in patients with locally relapsed hormone-refractory prostate cancer. This is an academic led single site study of a gene therapy injected directly into the prostate, followed by treatment with an alkylating agent.
Manchester ECMC at the Christie is leading on a phase II trial of adoptive T cell therapy using the patient's own T cells, genetically engineered to target the tumour associated antigen NY-ESO-1 (New York oesophageal squamous cell carcinoma 1)
Leeds ECMC has opened the REO 13 trial, looking at pre-operative administration of reovirus in patients due to undergo surgery for high grade glioma or brain metasteses . This is the first trial of its kind in the world.
Whilst the majority of studies in the network are drug studies, there are also a number of innovative surgery and radiotherapy trials.
The network is not only involved in novel combinations of drugs. Southampton ECMC is recruiting to a trial led by the Christie, combining the PARP inhibitor Olaparib with standard radiotherapy in patients with carcinoma of the oesophagus. This trial will assess the maximum tolerated dose of olaparib.
In a first of its kind, the team at Manchester has completed and published an international, multi-centre Phase II trial (FIZZ) to evaluate the efficacy and toxicity of fractionated 90Y-ibritumomab tiuxetan as initial therapy of follicular lymphoma (FL). The overall response rate was 94.4% and complete response rate was 69.4% and the therapy was well tolerated.
The team at Manchester have also developed at 26 gene signature for hypoxia, that is hoped will predict the patients most likely to benefit from hypoxia modifying treatment. This will be tested in the NIMRAD study in advanced head and neck cancer.
Patients with bladder cancer stand to benefit from studies in Oxford that have identified a biomarker that may help select those patients most likely to benefit from radiotherapy. With direct funding from CRUK, the marker assay is now being developed to appropriate standards and the relationship of the biomarker to clinical outcome is being further defined.
The ECMC at Imperial have been investigating epigenetic markers in susceptibility and patient stratification in ovarian cancer in phase II & III studies. In an international study, the team at Imperial helped demonstrate how DNA methylation patterns are notably distinct between subtypes of ovarian cancer, and have also indentified the first clear cell ovarian cancer-susceptibility gene (PMID: 23535649).
Research conducted at Barts & Brighton ECMC has revealed that high levels of integrin αvβ6 in breast tumours from HER-2 positive patients identifies those at high risk of developing secondary tumours (and poor survival) and have also shown that targeting αvβ6 with blocking antibody therapy (264RAD) could be effective against some of the most aggressive types of breast cancer - tumours were even eliminated in their combination therapy model.
The Edinburgh-Dundee ECMC have been working on building a predictive model for progression in breast cancer. This was presented at the 9th European Breast cancer Conference and has been submitted for patent protection.