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New clinical trial announced for patients with Malignant Melanoma

Posted on: 05 Dec 2016

New clinical trial announced for patients with Malignant Melanoma

 

Cork Cancer Research Centre (CCRC), which is based at University College Cork, has announced the launch of a new clinical trial for the treatment of malignant melanoma, which aims to significantly improve outcomes for patients with this form of skin cancer.

 

In Ireland there are approximately 630 new cases of melanoma diagnosed each year with 110 people losing their lives to the disease annually. Melanoma mortality is increasing very rapidly with the number of deaths per annum expected to reach 150 by 2020.

The new treatment being investigated involves a combination of Ipilimumab (“Ipi”, tradename Yervoy), a Bristol-Myers Squibb (BMS) drug, and tumour Electroporation, which is pioneered at CCRC. It aims to open up cancer cells with electrical pulses to facilitate the immunotherapy treatment to be even more effective, enabling the patient’s immune system to respond against the cancer. The study is supported by UCC, BMS and Breakthrough Cancer Research.

 

The trial, which is sponsored by BMS, has just commenced at Cork University Hospital (CUH) and is the first of its kind in the world. It is being led by Principal Investigator and Consultant Oncologist Dr Derek Power and Scientific Investigator Dr Declan Soden of the Cork Cancer Research Centre, who will enrol suitable patients from around the country.

 

 

 

IPI has been successfully used to date as a treatment of advanced melanoma in adults, significantly improving survival rates in up to 18% of patients who received the drug (*1). IPI is the first in a line of new immunotherapies that prevent tumours from shutting down the patient’s immune system when it’s attacking the cancer.

 

Electrochemotherapy (Electroporation combined with chemotherapy), which is pioneered at the Cork Cancer Research Centre with funding from Breakthrough Cancer Research, has received considerable attention in the last few years as an emerging therapy for use in cancer tumours. It involves delivering short bursts of electricity directly to the tumour making it porous and dramatically increasing its absorption of chemotherapy drugs.

 

The new study entitled “Enhanced Malignant Melanoma Immunological engagement using sequential therapy with Ipilimumab and electrochemotherapy”, or EMMIE for short, is a single centre trial aiming to establish the safety and efficacy of treating patients with advanced melanoma.

 

The trial of the new treatment regime has been approved by the Health Products Regulatory Authority, (formerly known as the Irish Medicine Board), the state agency which regulates and monitors the safe use of human and animal medicines in Ireland, and is being run with the support of BMS, who are providing the immunotherapy free of charge to University College Cork, and the Oncology Clinical Trials Unit in Cork University Hospital.

 

Support for this approach has also just been validated in a clinical paper published in Cancer Immunology Research (*2), which showed a 50% increase in survival rates in a trial group who received combined IPI with a locally ablative treatment.

 

Patients eligible to be included in the study will receive the licensed medicine, Ipilimumab, in accordance with its licenced use as a 1st or 2nd line treatment with electrochemotherapy being additionally applied to shrink the skin melanoma nodule.

 

Principal Investigator on the trial and Clinician and Consultant Medical Oncologist with Mercy and Cork University Hospitals, Dr Derek Power, welcomed the new developments in immunotherapy stating, ““It is only in the last few years that cancer researchers have unravelled one of the key protective mechanisms that cancers use to stop the immune system from recognising and destroying these abnormal cells. Cancer cells send out signals around the tumour to turn off locally present immune cells, which has, as a result, prevented immunotherapies, like Ipilimumab, from working. Overcoming this immune ‘cloaking’ of the tumour has become the key to making immune therapy work for patients.”

 

Dr Power continued, “Ipilimumab is already being used daily for patients across Ireland with established impacts for these patients. CCRC are at the forefront of research in relation to their electrochemotherapy treatment and we are excited at the synergy that will be created with the combined regime of these two treatments. We are already seeing good immune responses from Electrochemotherapy and with the addition of Ipilimumab we are excited to see the results from this enhanced treatment for patients.”

 

Dr Declan Soden, Principal Investigator and Manager at the Cork Cancer Research Centre welcomed the trial, stating, “Our research at the CCRC has shown that treating tumours with a short burst of energy can make them leaky or porous. This allows for a more focused absorption of chemotherapy allowing for a substantial reduction in the concentration required and essentially eliminating drug-based side effects for patients. Our studies have expanded from patients with skin cancers (breast, malignant melanoma) to endoscopically accessible cancers like colon, oesophageal. We hope to treat patients with other poor prognosis cancers using this approach in the near future.”

 

“This electrical pulse can also very significantly spark an immune engagement against the cancer, which in combination with immunotherapies like IPI, has been found to lead to better outcomes for the patients. The success of this trial should lead to other studies for patients suffering from poor prognosis cancer where there are currently limited options available” concluded Dr Soden.

 

Doctors with patients who may be suitable for this trial should refer them to Dr Power of the Oncology Clinical Trials Unit in Cork University Hospital or Dr Declan Soden of the Cork Cancer Research Centre in University College Cork. Patients can contact Dr Power through his PA at 021 492 2893.

 

 

Notes:

(1) The statement is taken from Dirk Schadendorf et al JCO 2015 Pooled Analysis of Long-Term Survival Data From Phase II and Phase III Trials of Ipilimumab in Unresectable or Metastatic Melanoma. Pooled analysis of OS adds to the evidence supporting the durability of long-term survival in a proportion of ipilimumab-treated patients with advanced melanoma. We observed a median OS of 11.4 months and an apparent plateau in the OS curve around year 3, when survival rates ranged from 20% to 26%, with follow-up to 10 years in some patients.

(2) Support for this approach has come from a clinical paper just published in Cancer Immunology Research - Local Tumor Treatment in Combination with Systemic Ipilimumab Immunotherapy Prolongs Overall Survival in Patients with Advanced Malignant Melanoma, Cancer Immunology Research 4(9) Sept 2016. Researchers went back and reviewed data on melanoma patients who had received systemic IPI along with concurrent targeted ablative treatment of their melanoma tumours. The data showed a doubling of survival in the group who received combined IPI with a locally ablative treatment (93wks v 42wks) (Cancer Immunology Research 4(6) Sept 2016).

http://cancerimmunolres.aacrjournals.org/content/4/9/744

 

About Electrochemotherapy

Electrochemotherapy is a type of chemotherapy that allows delivery of non-permeant drugs to the cell interior. It is based on the local application of short and intense electric pulses that transiently permeablize the cell membrane, thus allowing transport of molecules otherwise not permitted by the membrane[1][2]

·  Mir LM, Orlowski S, Belehradek J, Paoletti C; Orlowski; Belehradek Jr; Paoletti (1991). "Electrochemotherapy potentiation of antitumour effect of bleomycin by local electric pulses". European Journal of Cancer. 27 (1): 68–72. doi:10.1016/0277-5379(91)90064-k. PMID 1707289.

·  Sersa G, Cemazar M, Miklavcic D; Cemazar; Miklavcic (August 1995). "Antitumor effectiveness of electrochemotherapy with cis-diamminedichloroplatinum(II) in mice" (PDF). Cancer Research. 55 (15): 3450–5. PMID 7614485.

 

 Sharon, E et al. Immune checkpoint inhibitors in clinical trials. Chin J Cancer. 2014 Sep;33(9):434-44

2 Yervoy. Summary of Product Characteristics. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002213/WC500109299.pdf Last accessed October 2016