Adenocarcinoma - GEJPhase 2ELEVATENCT04984733
Temozolomide + Nivolumab in MGMT Methylated Oesophagogastric Cancer
A Phase 2 study testing Temozolomide, Temozolomide 50mg/m2/day and Temozolomide 3 month in people with Adenocarcinoma - GEJ and Cancer of Esophagus, run by University of Southampton at 1 site in United Kingdom.
Trial summary
An open label single arm phase II trial in patients with advanced unresectable previously treated oesophagogastric adenocarcinoma which is MGMT deficient. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adenocarcinoma - GEJ, Cancer of Esophagus
- What is being tested?
- Temozolomide, Temozolomide 50mg/m2/day and Temozolomide 3 month
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 28 Sep 2021to 23 Oct 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients ≥ 18 years of age
- Pathologically confirmed advanced unresectable or metastatic OGA
- MGMT methylation on archival tissue
- Mismatch repair proficient (MSI-normal or MMR intact)
- Previously treated with at least 3 months of platinum and fluoropyrimidine based chemotherapy for advanced disease and without evidence of disease progression.
- Measurable disease per RECIST 1.1.
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- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- Can swallow TMZ capsules
- Adequate organ function assessed within 7 days before randomization:
- White blood cell count (WBC) > 1.5 x 109/L
- Absolute neutrophil count (ANC) > 1.5 x 109/L
- Platelets ≥ 100 x 109/L
- Haemoglobin ≥ 90 g/L
- Measured/calculated creatinine clearance ≥ 60 mL/min (according to Cockroft-Gault formula).
- Total bilirubin within normal limits (if the patient has documented Gilbert's disease ≤ 1.5 x ULN or direct bilirubin ≤ 1.5 x ULN)
- Aspartate transaminase (AST) and/or alanine transaminase (ALT) ≤ 1.5 x ULN
- All toxicities (exception alopecia, and grade 2 fatigue, neuropathy and lack of appetite /nausea) attributed to prior anti-cancer therapy must have resolved to grade 1 (NCI CTCAE version 5.0) or baseline before administration of study drug.
- Women of childbearing potential (WOCBP) may be included following a confirmed menstrual period and must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin (HCG)). Pregnancy test must be within 24 hours prior to starting treatment. (A woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. However in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient).
- WOCBP should use one highly effective and one effective method of birth control during the study treatment period and for at least 5 months after the last dose of the study treatment.
- Female subjects who are breast feeding should discontinue nursing prior to the first dose of study treatment and until 5 months after the last dose of the study treatment.
- Men who are sexually active with a WOCBP must adhere to contraception during and for a period of 7 months after the last dose of the study treatment.
- Absence of any psychological, familial, sociological or geographical conditions potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.
- Written informed consent
Who cannot join
- Previous treatment with TMZ
- Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways
- Active central nervous system metastases
- Candidate for curative surgery
- Previous malignancies are excluded unless a complete remission was achieved at least 5 years prior to study entry. Adequately treated cervical carcinoma in situ, and localized non-melanoma skin cancer are not exclusion criteria, regardless of timepoint of diagnosis.
- Active, known, or suspected infectious or autoimmune disease (except for patients with Type I diabetes mellitus, residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment are permitted to enrol)
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- Conditions requiring systemic treatment with either corticosteroids (≥ 10 mg daily prednisolone or equivalent) or other immunosuppressive medications within 14 days of study drug administration
- Interstitial lung disease
- > Grade 1 peripheral neuropathy
- Positive test result for HBV or HCV indicating acute or chronic infection
- Known history of testing positive for HIV or known AIDS
- Known hypersensitivity to the components or excipients of co-trimoxazole, temozolomide or nivolumab. (Please refer to nivolumab IB and SmPC for TMZ and co-trimoxazole).
- Known hypersensitivity to dacarbazine (DTIC)
- Clinically significant abnormal 12-lead ECG. If clinically indicated, cardiac function assessment using either echocardiography or MUGA Scan, if clinically significant the patient is ineligible.
- In the past 6 months serious cardiac illness or medical condition including but not confined to:
- History of documented congestive heart failure (CHF)
- High-risk uncontrolled arrhythmias
- Angina pectoris requiring antianginal medication
- Clinically significant valvular heart disease
- Evidence of transmural infarction
- Poorly controlled hypertension (e.g. systolic >180mm Hg or diastolic greater than 100mm Hg)
- Patients with severe liver parenchymal damage
- Patients with severe renal insufficiency where repeated measurements of the plasma concentration cannot be performed
- Patients with a history of drug-induced immune thrombocytopenia with use of trimethoprim and/or sulfonamides.
- Patients with acute porphyria
- Patients with severe myelosuppression
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Cambridge University Hospitals NHS Foundation Trust
Cambridge, Cambridgeshire, CB2 0QQ
About this study
Official title: An Open Label Single Arm Phase II Trial in Patients With Advanced Unresectable Previously Treated Oesophagogastric Adenocarcinoma Which is MGMT Deficient
An open label single arm phase II trial in patients with advanced unresectable previously treated oesophagogastric adenocarcinoma which is MGMT deficient.
Read the 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.
- Conditions
- Adenocarcinoma - GEJ, Cancer of Esophagus
- Being tested
- Temozolomide, Temozolomide 50mg/m2/day, Temozolomide 3 month, Temozolomide 24month
- Keywords
- cancer, Oesophagogastric, Oesophagogastric adenocarcinoma,, MGMT deficient,, O6-methylguanine-DNA-methyltransferase, MGMT protein, human, MGMT methylated
- Medical subject headings
- Esophageal Neoplasms, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TemozolomideDrug
Also called Nivolumab
Metronomic TMZ 50mg/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. Patients who progress on TMZ will start monotherapy with nivolumab. Patients will remain on monotherapy with nivolumab or combination therapy until progression or up to a maximum of 24mths.
Temozolomide 50mg/m2/dayDrug
Also called Nivolumab
Metronomic TMZ 50mg/m2/day orally until progression then nivolumab 240mg IV until progression
Temozolomide 3 monthDrug
Also called Nivolumab
Metronomic TMZ 50mg/m2/day orally for 3 months, then nivolumab 240mg IV and TMZ until progression.
Temozolomide 24monthDrug
Also called Nivolumab
Metronomic TMZ 50mg/m2/day orally for 3 months, then nivolumab 240mg IV and TMZ until a maximum of 24 months
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | 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. Receives: Drug: Temozolomide; Drug: Temozolomide 50mg/m2/day; Drug: Temozolomide 3 month; Drug: Temozolomide 24month |
What is being measured
The primary outcome is the main question the study is designed to answer.
Tumour Response to nivolumab
To determine the anti-tumour activity of nivolumab, when given after temozolomide in patients with previously treated advanced oesophagogastric adenocarcinoma which are MGMT methylated.
Measured: 24 months
Secondary outcomes (1)
The percentage of patients who have achieved response
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.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jul 2021
- Study start28 Sep 2021
- Primary completion23 Oct 2024
- Study completion23 Oct 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Adenocarcinoma - GEJStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- An open-label, single arm, A'Hern single stage phase II design. Patients will receive TMZ priming followed by nivolumab to establish disease control rates.
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Southampton
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor
- Investigators
- Elizabeth Smyth, Principal investigator, Cambridge University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04984733
- Sponsor's protocol ID
- 61191
- Acronym
- ELEVATE
- Status last verified
- Mar 2025
- First submitted
- 13 Jan 2021
- Last updated
- 18 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label Single Arm Phase II Trial in Patients With Advanced Unresectable Previously Treated Oesophagogastric Adenocarcinoma Which is MGMT Deficient
- ClinicalTrials.gov ID
- NCT04984733
- Acronym / sponsor ID
- ELEVATE / 61191
- Conditions
- Adenocarcinoma - GEJ, Cancer of Esophagus
- Keywords
- cancer, Oesophagogastric, Oesophagogastric adenocarcinoma,, MGMT deficient,, O6-methylguanine-DNA-methyltransferase, MGMT protein, human, MGMT methylated
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- University of SouthamptonUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Study start
- 28 Sep 2021 (actual)
- Primary completion
- 23 Oct 2024 (actual)
- Study completion
- 23 Oct 2024 (actual)
- First posted
- 30 Jul 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- An open-label, single arm, A'Hern single stage phase II design. Patients will receive TMZ priming followed by nivolumab to establish disease control rates.
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Drug: Temozolomide, Drug: Temozolomide 50mg/m2/day, Drug: Temozolomide 3 month, Drug: Temozolomide 24monthMetronomic 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- Patients ≥ 18 years of age
- Pathologically confirmed advanced unresectable or metastatic OGA
- MGMT methylation on archival tissue
- Mismatch repair proficient (MSI-normal or MMR intact)
- Previously treated with at least 3 months of platinum and fluoropyrimidine based chemotherapy for advanced disease and without evidence of disease progression.
Key exclusion criteria (26 listed)
- Previous treatment with TMZ
- Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways
- Active central nervous system metastases
- Candidate for curative surgery
- Previous malignancies are excluded unless a complete remission was achieved at least 5 years prior to study entry. Adequately treated cervical carcinoma in situ, and localized non-melanoma skin cancer are not exclusion criteria, regardless of timepoint of diagnosis.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TemozolomideAlso: NivolumabMetronomic TMZ 50mg/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. Patients who progress on TMZ will start monotherapy with nivolumab. Patients will remain on monotherapy with nivolumab or combination therapy until progression or up to a maximum of 24mths. | Drug | Treatment |
| Temozolomide 50mg/m2/dayAlso: NivolumabMetronomic TMZ 50mg/m2/day orally until progression then nivolumab 240mg IV until progression | Drug | Treatment |
| Temozolomide 3 monthAlso: NivolumabMetronomic TMZ 50mg/m2/day orally for 3 months, then nivolumab 240mg IV and TMZ until progression. | Drug | Treatment |
| Temozolomide 24monthAlso: NivolumabMetronomic TMZ 50mg/m2/day orally for 3 months, then nivolumab 240mg IV and TMZ until a maximum of 24 months | Drug | Treatment |
Primary outcome
Tumour Response to nivolumab
Time frame: 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.
1 secondary outcome
The percentage of patients who have achieved response
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 May 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Elizabeth Smyth principal investigator
Cambridge University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Temozolomide, Temozolomide 50mg/m2/day and Temozolomide 3 month in people with Adenocarcinoma - GEJ and Cancer of Esophagus, run by University of Southampton at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 23 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Tumour Response to nivolumab (time frame: 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 May 2026.