ELEVATE

Title:  

ELEVATE: Temozolomide + nivolumab in MGMT methylated oesophagogastric cancer
 

Rationale:

In MGMT methylated oesophagogastric adenocarcinoma, temozolomide will induce a hypermutated state and increase sensitivity to nivolumab.

Description:

The aim of the trial is to determine the activity and safety maintenance TMZ dosing followed by nivolumab treatment to evaluate the potential for a future randomised trial against a standard of care control arm. The rationale to continue TMZ for 3 months or until PD is to evaluate the emergence of mismatch repair deficiency both with and without radiological PD, as clinically relevant MMRd may emerge before radiological progression. This will also reduce the number of patients who drop out due to symptomatic progressive disease.

Objectives:

Primary Objectives:

• To determine the anti-tumour activity of nivolumab, when given after temozolomide in patients with previously treated advanced oesophagogastric adenocarcinomawith MGMT methylation.

Secondary Objectives:

• To determine the effect of TMZ priming followed by nivolumab on disease control rates, progression-free and overall survival of patients with previously treated advanced oesophagogastric adenocarcinoma which is MGMT methylated.
• To assess the safety and toxicity of TMZ priming followed by nivolumab in oesophagogastric cancer patients.
• To describe the quality of life of patients on TMZ and/or nivolumab.

Trial Design:

An open label single arm phase II trial in patients with advanced unresectable previously treated oesophagogastric adenocarcinoma which is MGMT methylated.

Trial Status:

Open to recruitment

Population:

Patients with advanced, previously treated oesophagogastric cancer

This trial is supported by the National Institute for Health and Care Research