M6620 Plus Standard Treatment in Oesophageal and Other Cancer

Summary

Participation Requirements

Description

There is strong scientific rationale for combining ATR inhibitors with DNA damaging agents such as radiation and cisplatin. In particular, ATR inhibition has been shown to be cytotoxic to tumor cells with an impaired DNA damage response, such as those with deficiency in the ATM- or p53 pathway. The ...

There is strong scientific rationale for combining ATR inhibitors with DNA damaging agents such as radiation and cisplatin. In particular, ATR inhibition has been shown to be cytotoxic to tumor cells with an impaired DNA damage response, such as those with deficiency in the ATM- or p53 pathway. The high incidence of p53 mutations and the fact that cisplatin and radiation are key therapeutics, makes oesophageal cancer an attractive tumor type to test the activity of an ATR inhibitor. Given the reported synthetic lethal relationship between ATM and ATR, it is likely that ATR inhibition in an ATM- or p53- deficient background will offer a specific and effective way of targeting OAC and SCC of the oesophagus, and enhance the current standard of care. The trial will be divided into three stages. Stage A1 will explore the combination of M6620 plus radiotherapy in the palliative setting and Stage A2 will explore the combination of M6620 plus chemotherapy in the palliative setting. Stage B, will explore the combination of all 3 (M6620 plus chemoradiotherapy in the radical setting). In Stage A1 of the study M6620 will be combined with radiotherapy for the first time and the starting dose will be 140mg/m2 M6620, which has been well-tolerated. M6620 will be administered with daily palliative radiotherapy during this stage in order to study the specific interaction of M6620 with radiotherapy (acting as the DNA damaging agent during this trial stage). In Stage A2 of the study, M6620 will be combined with Cisplatin and Capecitabine combination chemotherapy for the first time; with a starting dose of 90mg/m2 M6620. M6620 will be administered 24 hours post cisplatin infusion, aiming to achieve maximum treatment benefit. Stage A1 and A2 together will help give an indication of a toxicity profile before administration with chemoradiotherapy (Stage B).

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