The purpose of this international study is to determine if the combination of regorafenib and nivolumab is more effective than standard chemotherapy in prolonging overall survival in a broad group of participants with AGOC, who have progressed after treatment with standard anti-cancer therapy. In the INTEGRATE study, regorafenib alone was shown to be effective in prolonging the progression-free period in people with AGOC following standard anti-cancer therapy (i.e. it delayed tumour growth), and demonstrated a potential benefit on long term survival. Recent research has shown the early results from this combination of regorafenib & nivolumab may improve outcomes for cancer patients. INTEGRATE IIb will investigate this effect further in a larger group of participants with AGOC. INTEGRATE IIb MASTER Participant Information and Consent Form, Version 2.0 9th Nov 2020 Royal Darwin Hospital Participant Information and Consent Form, Version 2.0, 8 th April 2022 Page 3 of 26 The study aims to determine: i. Whether the combination of regorafenib/nivolumab is likely to help people with AGOC live longer; ii. The effects of this treatment on progression-free survival; iii. The numbers of participants responding to the treatment iv. The effects of this treatment on quality of life v. The side effects and tolerability of this treatment vi. Molecular differences (e.g. variations in genes or proteins) that may account for the effects of this treatment vii. Differences in the costs of care for people on this treatment. We plan to enrol 450 participants in the study from, but not limited to; Australia, New Zealand, South Korea, Japan, Taiwan, Canada, USA, Germany, Belgium, Spain, France, Switzerland, Netherlands and Italy. 1-5 participants are planned to be enrolled at Royal Darwin Hospital. Medications, drugs and devices have to be approved for routine use by the Australian Therapeutic Goods Administration (TGA). Neither regorafenib nor nivolumab are approved in Australia or other countries for the treatment of AGOC, thus, their use in this study is investigational. Regorafenib is, however, approved for certain types of bowel cancer, gastrointestinal stromal tumours (GIST), and a type of liver cancer (hepatocellular carcinoma or HCC), and Nivolumab is approved for skin, lung, kidney, head/neck, blood, bladder, and liver cancers in Australia and other countries.

https://hdl.handle.net/10137/12765

Advanced Gastro-Oesophageal Cancer (AGOC)

Randomised Phase III Controlled Trials of Regorafenib containing regimens versus standard care in Refractory Advanced Gastro-Oesophageal Cancer (AGOC)

Interventional/Clinical trials research

Project