The details about the Phase 1 study announced yesterday are available at:
Our main objective in this study is to see if NOX66 can make tumours respond to chemotherapy once they have become fully drug-resistant, and to do so using low dosages of chemotherapy.
That’s an ambitious and novel objective, but one that in my opinion is very achievable. And if we achieve that, then it would usher in a new era in the management of cancer – offering greater certainty over the response to chemotherapy, including when all treatment options have been exhausted, and to do so with the promise of being able to avoid significant chemotherapy side-effects.
In the test-tube, idronoxil sensitises drugs such as carboplatin by thousands of times, meaning that the amount of carboplatin that needs to be added to cancer cells to achieve 100% kill can be reduced by over 2000-times in the presence of idronoxil. Prostate cancer cells also have been shown to accumulate more cisplatin (sister drug of carboplatin) in the presence of idronoxil. Collectively this means that a combination of idronoxil and carboplatin forms a powerful anti-cancer duo.
The clinical study in question is based on the simple proposition that as long as we can deliver idronoxil to the cancer cell in the body in an active form, then it should sensitise those cancer cells to carboplatin to the same extent as it does in the laboratory. That is what we hope to do with NOX66.
Idronoxil sensitises cancer cells to all commonly used cytotoxic chemotherapies, but we have chosen carboplatin because it is one of the most commonly used chemotherapies; it also is one of the most toxic, in particular affecting bone marrow, resulting in low levels of red and white blood cells.
15 patients will be recruited to start with and these will be drawn from patients with cancers of the breast, lung, prostate, ovary, and head and neck. Each patient will have metastatic disease (secondary tumours) and have stopped responding to standard therapies.
The study starts with a Phase 1a arm that involves using NOX66 on its own. Patients get 2 weeks of NOX66 treatment at 1 of 3 different dosages. We are not expecting any toxicity with any of the 3 dosages given the safe history of idronoxil in several hundred patients at high doses. But given that we are delivering the idronoxil in a way that we expect to lead to considerably higher levels of active drug than achieved previously, we need to go back and look at safety.
If the 3 dosages of NOX66 are well tolerated, then patients progress immediately (after 3 weeks) onto the Phase 1b arm of the study where they continue to receive the same starting dosage of NOX66, but now in combination with carboplatin, which they will receive monthly for 6 months.
The normal carboplatin dosage varies between AUC of 4-6. The term ‘AUC’ means ‘area under the curve’ and refers to the rate at which carboplatin leaves the body in the urine. An AUC of 4 obviously is likely to be safer but less effective than an AUC of 6. In patients with well-established tumours that have become unresponsive to chemotherapy, an AUC of 4 generally would be considered ineffective.
We will be starting with an AUC of 4 and patients will receive this for 3x 1-monthly treatments. Patients will undergo a CT scan before and after this period and the effect of treatment on the disease process determined by measuring any change in the size or number of tumours.
If there has been anything less than a complete response, the patients will progress onto the higher dosage of carboplatin (AUC = 6) for a further 3x 1-monthly treatments, followed by another CT scan.
This approach delivers a matrix involving 3x NOX66 dosages, 2x carboplatin dosages and potentially 5x cancer types. From this matrix we propose to select 2 situations with the most promising clinical outcomes and expand both into 2 cohorts of 15 patients each to comprise a Phase 2a arm.
Safety (eg. levels of red and blood cell cells), blood levels of idronoxil, and blood levels of potential biomarkers also will be measured throughout the study. ‘Biomarkers’ are known biochemical markers of idronoxil activity that will be assessed for their predictive value in terms of clinical response.