Rigosertib for RDEB SSC (2022)

This trial offers six people with incurable RDEB skin cancer an experimental drug, rigosertib, to see if it can reduce the size of their tumours without significant side effects. If successful this treatment has the potential to become a therapy for the treatment of RDEB cancer.

This clinical trial aims to recruit at least 6 people with RDEB skin cancer that has not responded to standard treatments. They will take two rigosertib tablets per day at home for two weeks, stop the tablets for a week, then have a hospital check-up and repeat the three week course over several months/years. Rigosertib side effects including any specific to EB will be investigated. At every other hospital visit (every six weeks), the size of the tumour will be measured with a scan. Biopsies may be taken or the tumour itself removed if it has become small enough.

About our funding:

Research leader	Dr Andrew South
Institution	Thomas Jefferson University, Philadelphia USA
Type of EB	RDEB
Patient involvement	Yes - phase II clinical trial
Funding amount	$557,842
Project length	5 years
Start date	April 2017
DEBRA internal ID	South3

Final progress summary:

Five years of funding allowed recruitment of the first patient in 2021, who remains cancer free after 19 months of receiving treatment directly into their blood (intravenously). A second patient began treatment with tablets in September 2022 and the trial continues with separate funding.
Researchers published results of their work on rigosertib, funded by DEBRA, in 2019 and presented their work as a poster at the Austrian Society of Dermatology and Venerology Annual Conference in November 2021.
The manufacturer of rigosertib (Onconova Therapeutics) announced the preliminary results in December 2021.
The clinical trial is registered and still recruiting.

About our researchers:

Lead researcher:

Dr Andrew South is an Associate Professor at Thomas Jefferson University, Philadelphia. His primary interests are to understand the events that lead to the development and progression of SCC, particularly those cancers arising in patients living with RDEB. Dr South has worked at institutions with a strong history of EB research, in London, Scotland, and now Philadelphia, and is committed to finding cures to this devastating group of diseases through application of basic scientific research.

Co-researchers:

Prof Johann Bauer is head of the Department of Dermatology of the University Hospital Salzburg. He built up and has headed the research group of the EB-House Austria, which consists of more than 20 scientists working on EB research. His main interest is the development of a safe and applicable gene therapy for all forms of EB. Moreover the group in Salzburg works on small molecule based approaches to alleviate the symptoms of EB in order to enhance the quality of life of the patients and on developing therapies for RDEB associated aggressive SCCs.

Prof Jemima Mellerio is a consultant dermatologist and professor at St John’s Institute of Dermatology, Guy’s and St Thomas’ NHS Foundation Trust. She has over 20 years working clinically in the field of EB and other genetic skin diseases, as well as a research background looking at the molecular basis of different types of EB, and clinical trials into newer therapies for EB such as fibroblast and mesenchymal stromal cell therapy. She is dedicated to continuing this work to develop more effective treatments for all types of EB.

Why this research is important:

Work started by this project has the potential to lead to an approved therapy for the treatment of RDEB cancer, a goal that Debra UK started with in the early 2000s.

Dr Andrew South

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Researcher’s abstract:

Grant title: “First in EB” phase II trial of rigosertib for RDEB SCC.

We propose to perform a small, "first in EB" trial of an experimental drug called rigosertib for the treatment of EB cancer. The drug is an inhibitor of different processes that are essential for cancer cell growth. Rigosertib has been in clinical trial for a number of other cancers, principally myelodysplastic syndrome (a cancer of the blood) and therefore the company that developed the drug, Onconova, have good experience of using rigosertib in patients.

We have identified that in the laboratory rigosertib kills EB cancer cells and doesn't harm normal EB skin cells. This project will test whether rigosertib can kill cancer cells in an EB patient and whether the drug can be tolerated by patients - can patients take oral rigosertib (as tablets, twice a day) without significant impact to daily routine. If rigosertib can kill cancer cells in an EB patient we will examine the cancer and the patient to try and identify an apsect of either which can be used to predict whether future patients can benefit from this treatment.

Researcher’s final progress update:

Debra funded the initiation of the first clinical trial of an experimental therapy for the treatment of EB cancer. The project was called "First in EB" Phase II trial of Rigosertib for RDEB SCC. The drug is an inhibitor of different processes that are essential for cancer cell growth and we have shown that all RDEB cancer cells respond to this drug in the laboratory. Rigosertib had been in clinical trial for a number of other cancers and showed a very mild side effect profile.

Although we experienced significant delays in setting up this trial, confounded by the Covid-19 pandemic, we finally recruited the first patient in 2021. The first patient to be treated (in Austria) received rigosertib intravenously and showed a complete response, meaning their cancer disappeared with treatment. The patient remains cancer free after 19 months of receiving treatment. Separate funding has supported the treatment of a second patient, which began in September 2022 and this time with oral drug. This patient is showing similar signs of a rapid response to the drug and we remain optimistic that rigosertib may become an effective option for RDEB cancer therapy. (From 2022 Final Progress Report.)