Genesis of a Clinical Trial: OXTOX
To successfully obtain funding for academic research and the establishment of a clinical trial takes a considerable amount of effort, time and collaboration across multi-disciplinary teams. Follow the genesis of an AGITG clinical trial, OXTOX (Can Oxaliplatin dose reduction and neurotoxicity be reduced with ibudilast in people with metastatic colorectal cancer? A phase II randomised study) from identification of the problem to obtaining funding for a study supported by the AGITG Innovation Fund.
Oxaliplatin chemotherapy improves survival but causes acute neuropathy (pins and needles and pain on touching or swallowing cold objects or fluids) and chronic chemotherapy-induced peripheral neuropathy (CIPN) in most people receiving the drug. This causes numbness, discomfort, and pain especially in the hands and feet, which can last for months to years after stopping treatment.
Studies done using animal models suggest ibudilast, a tablet, when given with oxaliplatin can prevent and treat neurotoxicity. This may mean more oxaliplatin can be delivered, thus improving survival in people with colorectal cancers.
Step 1. Identification of a gap in research
In her role leading the Sydney Survivorship Centre, Professor Janette Vardy was surprised when patient-reported outcomes indicated how big an issue peripheral neuropathy was for cancer patients. She was interested in looking into this further.
Step 2. Literature review
A search for information on treatment for peripheral neuropathy showed that there was no evidence-based treatment available. There was a distinct gap in knowledge.
Step 3. Pre-clinical research
Professor Vardy’s PhD student Dr Christina Teng was studying peripheral neuropathy. Together with Dr Ian Johnston at the University of Sydney, they conducted an animal study which found that ibudilast was successful in reducing peripheral neuropathy in rats.
Step 4. Pilot study
Researchers conducted a pilot study looking at the impact of ibudilast on patients to ensure that it was a safe treatment. This was a pharmacokinetic study that also collected data on patient reported outcomes including peripheral neuropathy.
Step 5. A research team is assembled
Professor Vardy assembled a research team, a mixture of medical oncologists and researchers that had the knowledge to move the concept forward. Five clinicians from sites with a focus on colorectal cancer treatment joined the team as they recognised that this was such a huge problem for their patients for which there is very little evidence-based treatment.
Step 6. Application to the AGITG Innovation Fund
Professor Vardy prepared a grant application for the 2018 AGITG Innovation Fund and was awarded a $200,000 grant. The AGITG Innovation Fund is made possible by the generosity of donors.
Step 7. A clinical trial is started
The phase II clinical trial is now open for enrolment with funding from the AGITG Innovation Fund. This was the last step in a process that began with Professor Vardy noticing a problem that was substantially affecting patients who did not have other treatments available.