Temozolomide + Nivolumab in MGMT Methylated Oesophagogastric Cancer

Phase 2

Recruiting

• Conditions: Adenocarcinoma - GEJ; Cancer of Esophagus
• Interventions: Drug: Temozolomide; Drug: Temozolomide 50mg/m2/day; Drug: Temozolomide 3 month; Drug: Temozolomide 24month

• Registration Number: NCT04984733
• Lead Sponsor: University of Southampton

Brief Summary

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

Detailed Description

The aim of the ELEVATE trial is to determine the activity and safety of 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.

Study Timeline

• Study First Submitted: 2021-01-13
• Study First Submitted QC: 2021-07-28
• Study First Posted: 2021-07-30
• Study Start: 2021-09-28
• Status Verified: 2023-11
• Last Update Submitted: 2023-11-28
• Last Update Posted: 2023-11-29
• Primary Completion: 2024-07
• Study Completion: 2026-07

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 18

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment	Temozolomide 50mg/m2/day	Metronomic TMZ 50mg/m2/day orally for 3 months, then nivolumab 240mg IV until progression. Metronomic TMZ 50mg/m2/day orally until progression then nivolumab 240mg IV until progression. Patients who progress on TMZ will start monotherapy with nivolumab. Metronomic TMZ50mg/m2/day orally for 3 months, then nivolumab 240mg IV +/- TMZ until progression. Patients who don't progress on TMZ will commence with combination treatment; TMZ + Nivolumab at 3 mths until they progress Metronomic TMZ 50mg/m2/day orally for 3 months, then nivolumab 240mg IV +/- TMZ until 24 months. Patients will remain on combination therapy up to a maximum of 24mths.
Treatment	Temozolomide 3 month	Metronomic TMZ 50mg/m2/day orally for 3 months, then nivolumab 240mg IV until progression. Metronomic TMZ 50mg/m2/day orally until progression then nivolumab 240mg IV until progression. Patients who progress on TMZ will start monotherapy with nivolumab. Metronomic TMZ50mg/m2/day orally for 3 months, then nivolumab 240mg IV +/- TMZ until progression. Patients who don't progress on TMZ will commence with combination treatment; TMZ + Nivolumab at 3 mths until they progress Metronomic TMZ 50mg/m2/day orally for 3 months, then nivolumab 240mg IV +/- TMZ until 24 months. Patients will remain on combination therapy up to a maximum of 24mths.
Treatment	Temozolomide 24month	Metronomic TMZ 50mg/m2/day orally for 3 months, then nivolumab 240mg IV until progression. Metronomic TMZ 50mg/m2/day orally until progression then nivolumab 240mg IV until progression. Patients who progress on TMZ will start monotherapy with nivolumab. Metronomic TMZ50mg/m2/day orally for 3 months, then nivolumab 240mg IV +/- TMZ until progression. Patients who don't progress on TMZ will commence with combination treatment; TMZ + Nivolumab at 3 mths until they progress Metronomic TMZ 50mg/m2/day orally for 3 months, then nivolumab 240mg IV +/- TMZ until 24 months. Patients will remain on combination therapy up to a maximum of 24mths.
Treatment	Temozolomide	Metronomic TMZ 50mg/m2/day orally for 3 months, then nivolumab 240mg IV until progression. Metronomic TMZ 50mg/m2/day orally until progression then nivolumab 240mg IV until progression. Patients who progress on TMZ will start monotherapy with nivolumab. Metronomic TMZ50mg/m2/day orally for 3 months, then nivolumab 240mg IV +/- TMZ until progression. Patients who don't progress on TMZ will commence with combination treatment; TMZ + Nivolumab at 3 mths until they progress Metronomic TMZ 50mg/m2/day orally for 3 months, then nivolumab 240mg IV +/- TMZ until 24 months. Patients will remain on combination therapy up to a maximum of 24mths.

Primary Outcome Measures

Name	Time	Method
Tumour Response to nivolumab	24 months	To determine the anti-tumour activity of nivolumab, when given after temozolomide in patients with previously treated advanced oesophagogastric adenocarcinoma which are MGMT methylated.

Secondary Outcome Measures

Name	Time	Method
The percentage of patients who have achieved response	6 months	The Disease control rate determine the effect of TMZ priming followed by nivolumab on disease control rates of patients with previously treated advanced oesophagogastric adenocarcinoma which is MGMT methylated.; Disease control rate, according to RECIST v1.1 and iRECIST, 6 months after starting nivolumab, and 3 months after starting TMZ, respectively.

Trial Locations

Locations (1)

Cambridge University Hospitals NHS Foundation Trust; 🇬🇧 Cambridge, Cambridgeshire, United Kingdom