CancerPhase 2EMERGENCT03812796
Epigenetic Modulation of the immunE Response in GastrointEstinal Cancers (EMERGE)
A Phase 2 study testing Domatinostat and Avelumab in people with Cancer and GI Cancer, run by Royal Marsden NHS Foundation Trust at 2 sites in United Kingdom.
Trial summary
A multicenter phase II non-randomised trial assessing the efficacy of domatinostat (4SC-202) plus avelumab in patients with GI cancer Read more about this study
- Who is it for?
- Ages 18 years and older
- What is being tested?
- Domatinostat and Avelumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 75 participants
- Where
- 2 sitesUnited Kingdom
- Study dates
- 11 Jan 2019to 30 Nov 2021
- 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
- Male/female patients aged ≥18 years ii. Histologically confirmed gastric, gastro-oesophageal junction or oesophageal adenocarcinoma (referred to as oesophagogastric adenocarcinoma (OGA) in this protocol) or colorectal adenocarcinoma (referred to as CRC in this protocol) iii. Agrees to undergo biopsies for translational endpoints iv. Tumour must be mismatch repair proficient assessed using a validated test such as immunohistochemistry for mismatch repair proteins or microsatellite instability testing v. Tumours should be advanced and inoperable or metastatic vi. Patients must have received at least one prior chemotherapy treatment for their cancer, have no established treatment option, or decides against an established treatment option.
- Adequate bone marrow function:
- Absolute neutrophil count (ANC) ≥1.5 x109/L
- White blood count >3x109/L
- Platelets ≥100x109/L
- Haemoglobin (Hb) ≥9g/dl (can be post-transfusion) viii. Adequate renal function: Creatinine Clearance o ≥30ml/min is required. This may be calculated as per local practice, if calculated CrCl is <60ml/min then EDTA is required to demonstrate CrCl of ≥30ml/min If available, the EDTA clearance should always take precedence over the creatinine clearance.
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- Adequate liver function
- Serum bilirubin ≤1.5x ULN b. ALT/AST ≤2.5x ULN or ALT/AST ≤5x ULN if metastatic disease to liver x. Adequate coagulation profile
- International Normalised Ratio (INR) < 1.5
- Activated Prothrombin Time (APTT) < 1.5xULN xi. Patients on oral anticoagulation are advised to change to low molecular weight heparin prior to study entry to be eligible xii. ECOG performance status 0-1 xiii. Patient is fit to undergo all protocol investigations and receive all protocol treatment based on the assessment oncology clinics xiv. Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all the pertinent aspects of the trial prior to enrolment.
- Willingness and ability to comply with the protocol for the duration of the study including scheduled visits, examinations, investigations and treatment plans xvi. Pregnancy must be excluded with a negative serum pregnancy test, within 7 days before initiation of therapy, if the risk of conception exists. Sexually active female patients must be surgically sterile or be postmenopausal or must agree to use highly effective contraception which must be used for 10 days before the negative pregnancy test. Sexually active male patients must be surgically sterile or must agree to use highly effective contraception, i.e. methods with a failure rate of <1% per year (see section 6.4 for full definition and examples of highly effective contraception). Highly effective contraception must be agreed to be used throughout the study and for 30 days after last avelumab treatment if risk of conception exists. Female patients of child-bearing potential should be strictly advised to use a highly effective contraceptive measure, from the time of screening to 30 days after the last dose of trial treatment. If the patient uses a hormonal contraceptive method, the patient's partner should additionally use a condom. Male patients with partners of child bearing potential should be strictly advised to use barrier contraception in addition to having their partner use another method of contraception during the trial and for three months after the last dose. Male patients should also be advised to abstain from sexual intercourse with pregnant or lactating women, or to use condoms.
Who cannot join
- Any contraindication or known hypersensitivity reaction to any of the study drugs ii. Persisting toxicity relating to prior therapy of >grade 1 CTCAE version 4.03 except alopecia of any grade and neuropathy ≤ grade 2, or other grade ≤2 not constituting a safety risk based on investigators judgement iii. Any prior treatment with immunotherapy including anti-PD-1or PD-L1 therapy or other immunomodulatory drugs.
- All subjects with brain metastases, except those meeting the following criteria:
- Brain metastases that have been treated locally and are clinically stable for at least 2 weeks prior to enrolment
- No ongoing neurological symptoms that are related to the brain localization of the disease (sequelae that are a consequence of the treatment of the brain metastases are acceptable)
- Subjects must be either off steroids or on a stable or decreasing dose of <10mg daily prednisone (or equivalent)
- Known severe hypersensitivity reactions to monoclonal antibodies (Grade ≥ 3 NCI CTCAE v 4.0), any history of anaphylaxis, or uncontrolled asthma (i.e., 3 or more features of partially controlled asthma) vi. Patients who have received chemotherapy or radiotherapy for a previous malignancy in the past 3 years.
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- Any immunodeficiency disorder viii. Any active, known or suspected autoimmune disease that might deteriorate when receiving immunostimulatory agent, with the following exceptions:
- Patients with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible
- Patients requiring hormone replacement with corticosteroids are eligible if the steroids are administered only for the purpose of hormonal replacement and at doses ≤10mg (or equivalent) of prednisolone per day
- Administration of steroids through a route known to result in minimal systemic exposure (topical, intranasal, intra-ocular, intra-articular or inhalation) are acceptable. Steroids as pre-medication for hypersensitivity reactions e.g. CT contrast are also acceptable.
- Prior organ transplantation, including allogeneic stem-cell transplantation x. Active infection requiring systemic therapy xi. History of inflammatory bowel disease xii. Patients with a history of interstitial lung disease or radiological evidence of pulmonary fibrosis xiii. Cerebrovascular disease (including transient ischaemic attacks (TIA) and strokes) within the previous 6 months xiv. Cardiovascular diseases as follows:
- Myocardial infarction within the previous 6 months
- Unstable angina
- Congestive heart failure ≥NYHA Classification Class II
- Serious cardiac arrhythmia requiring medication (for example, ventricular tachycardia, supraventricular tachycardia or atrial fibrillation with a resting heart rate > 110bpm) xv. Current signs or symptoms of any other severe progressive or uncontrolled hepatic, haematologic, gastrointestinal, endocrine, respiratory or cardiac disease, which in the opinion of the investigator, might impair the subject's tolerance of trial treatment or procedures.
- Major surgery, major trauma or open biopsy within 28 days prior to registration (not including staging laparoscopy) xvii. Evidence of bleeding diathesis or coagulopathy xviii. Active non-healing wound, ulcer or bone fracture requiring therapy xix. Known positive tests for human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome, hepatitis A or C virus, acute or chronic active hepatitis B infection xx. Use of live attenuated vaccine within 28 days of initiation of study therapy, or anticipation that a live attenuated vaccine will be required during the study xxi. Current lactation (patients that discontinue breastfeeding may be eligible) xxii. Other severe acute or chronic medical conditions or psychiatric conditions including recent (within the past year) or active suicidal ideation or behaviour; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
Trial locations and contacts
2 sites in 1 country.
United Kingdom2 sites, 2 recruiting
- Recruiting
The Royal Marsden Hospital NHS Foundation Trust
London, SW3 6JJ
David Cunningham, 020 8642 6011, david.cunningham@rmh.nhs.uk
Claire Saffery, 020 8642 6011 ext. 4480, Claire.Saffery@rmh.nhs.uk
- Recruiting
The Royal Marsden Hospital NHS Foundation Trust
Sutton, Surrey, SM2 5PT
David Cunningham, 020 8642 6011, david.cunningham@rmh.nhs.uk
Claire Saffery, 020 8642 6011 ext. 4480, Claire.Saffery@rmh.nhs.uk
About this study
A multicenter phase II non-randomised trial assessing the efficacy of domatinostat (4SC-202) plus avelumab in patients with GI cancer
Read the detailed description
During this phase II non randomised trial patients with microsatellite stable colorectal or gastroesophageal cancer which has previously been treated with chemotherapy will be treated with domatinostat plus avelumab.
- Being tested
- Domatinostat, Avelumab
- Medical subject headings
- Neoplasms, Gastrointestinal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DomatinostatDrug
Also called 4SC-202
Domatinostat is an oral tablet which will be given at a variable dose during the Phase IIA safety run in phase of the trial.
During the Phase IIB efficacy phase of the trial patients will be treated with domatinostat at the safe and tolerated combination dose identified during the Phase IIA safety run in phase.
AvelumabDrug
Avelumab is a monoclonal antibody which is given via an intravenous infusion at a dose of 10mg/kg every two weeks on the first day of a two week cycle. (Day 1 q 14d) from Cycle 2 onwards.
| Study group | Role | What they receive |
|---|---|---|
| Domatinostat plus Avelumab | Experimental | This is a multicentre open-label, phase II non-randomised clinical trial domatinostat plus avelumab (two separate cohorts in phase IIB part of trial). Receives: Drug: Domatinostat; Drug: Avelumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety run-in phase: To establish a safe and tolerable dose of domatinostat in combination with avelumab for use in the main (Phase IIB efficacy) phase of the trial
Progression through dosing levels will be determined by the occurrence of dose limiting toxicities in the study population.
Measured: The DLT period is 28 days following the first treatment with domatinostat and avelumab
Main Phase IIB (efficacy) phase: Objective response rate using RECIST 1.1 criteria
ORR defined as the proportion of patients with either CR or PR (assessed according to RECIST 1.1) by 6 months from combination treatment initiation. The best ORR will be presented as a proportion along side a 95% confidence interval
Measured: 6 months
Secondary outcomes (5)
Number of patients with adverse events (according to NCI-CTCAE version 4) as a measure of safety and tolerability
Safety of domatinostat and avelumab will be assessed by summarizing adverse events as a proportion
Measured: Up to 90 days after last dose
Progression free survival according to RECIST 1.1
PFS will be summarized using Kaplan Meier methods, presenting median survival with 95% confidence intervals. PFS is defined as the time from day of first treatment to disease progression or death from any cause. Patients without an event will be censored on day of last radiological follow up
Measured: upto 2 years
Overall survival
OS will be summarized using Kaplan Meier methods, presenting median survival with 95% confidence intervals. OS is defined as the time from say of first treatment to death from any cause. Alive patients will be censored at the last follow up date
Measured: upto 2 years
Disease control rate
The proportion of patients with best disease control (CR, PR or SD) at 6 months and 12 months from initiation of combination treatment will be presented with a 95% confidence interval
Measured: At 6 and 12 months on treatment
Duration of objective response according to RECIST 1.1
DoOR will be summarized using Kaplan Meier methods. DoOR is defined as the time between the initial response to treatment and subsequent disease progression or relapse. Patients without an event will be censored on day of last radiological assessment
Measured: upto 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jan 2019
- Study start11 Jan 2019
- Primary completion30 Nov 2021 (estimated)
- Study completion30 Nov 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for CancerStudies of the same condition, open and under way.
- More trials run by Royal Marsden NHS Foundation TrustThe sponsor's other registered studies.
- 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
- Non-randomised
- Masking
- None (open label)
- Enrolment
- 75 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Royal Marsden NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Collaborators
- 4SC AG, Merck KGaA, Darmstadt, Germany
- Responsible party
- Sponsor
- Investigators
- David Cunningham, Principal investigator, Consultant Medical Oncologist
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03812796
- Sponsor's protocol ID
- CCR 4745
- Acronym
- EMERGE
- Status last verified
- Feb 2019
- First submitted
- 9 Apr 2018
- Last updated
- 5 Feb 2019
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Cartwright E, Slater S, Saffery C, Tran A, Turkes F, Smith G, Aresu M, Kohoutova D, Terlizzo M, Zhitkov O, Rana I, Johnston EW, Sanna I, Smyth E, Mansoor W, Fribbens C, Rao S, Chau I, Starling N, Cunningham D. Phase II trial of domatinostat (4SC-202) in combination with avelumab in patients with previously treated advanced mismatch repair proficient oesophagogastric and colorectal adenocarcinoma: EMERGE. ESMO Open. 2024 Apr;9(4):102971. doi: 10.1016/j.esmoop.2024.102971. Epub 2024 Mar 21.
PubMed 38518549
Study at a glance
From the registry record, last updated by the sponsor on 5 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Epigenetic Modulation of the immunE Response in GastrointEstinal Cancers (EMERGE)
- ClinicalTrials.gov ID
- NCT03812796
- Acronym / sponsor ID
- EMERGE / CCR 4745
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 75 participants (estimated)
- Lead sponsor
- Royal Marsden NHS Foundation TrustUniversity, hospital or other
- Collaborators
- 4SC AG, Merck KGaA, Darmstadt, Germany
- Study start
- 11 Jan 2019 (actual)
- Primary completion
- 30 Nov 2021 (estimated)
- Study completion
- 30 Nov 2021 (estimated)
- First posted
- 23 Jan 2019 (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.
A multicenter phase II non-randomised trial assessing the efficacy of domatinostat (4SC-202) plus avelumab in patients with GI cancer
Detailed description
During this phase II non randomised trial patients with microsatellite stable colorectal or gastroesophageal cancer which has previously been treated with chemotherapy will be treated with domatinostat plus avelumab.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Non-randomised
| Arm | Type | Receives |
|---|---|---|
| Domatinostat plus Avelumab | Experimental | Drug: Domatinostat, Drug: AvelumabThis is a multicentre open-label, phase II non-randomised clinical trial domatinostat plus avelumab (two separate cohorts in phase IIB part of trial). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Male/female patients aged ≥18 years ii. Histologically confirmed gastric, gastro-oesophageal junction or oesophageal adenocarcinoma (referred to as oesophagogastric adenocarcinoma (OGA) in this protocol) or colorectal adenocarcinoma (referred to as CRC in this protocol) iii. Agrees to undergo biopsies for translational endpoints iv. Tumour must be mismatch repair proficient assessed using a validated test such as immunohistochemistry for mismatch repair proteins or microsatellite instability testing v. Tumours should be advanced and inoperable or metastatic vi. Patients must have received at least one prior chemotherapy treatment for their cancer, have no established treatment option, or decides against an established treatment option.
- Adequate bone marrow function:
- Absolute neutrophil count (ANC) ≥1.5 x109/L
- White blood count >3x109/L
- Platelets ≥100x109/L
Key exclusion criteria (16 listed)
- Any contraindication or known hypersensitivity reaction to any of the study drugs ii. Persisting toxicity relating to prior therapy of >grade 1 CTCAE version 4.03 except alopecia of any grade and neuropathy ≤ grade 2, or other grade ≤2 not constituting a safety risk based on investigators judgement iii. Any prior treatment with immunotherapy including anti-PD-1or PD-L1 therapy or other immunomodulatory drugs.
- All subjects with brain metastases, except those meeting the following criteria:
- Brain metastases that have been treated locally and are clinically stable for at least 2 weeks prior to enrolment
- No ongoing neurological symptoms that are related to the brain localization of the disease (sequelae that are a consequence of the treatment of the brain metastases are acceptable)
- Subjects must be either off steroids or on a stable or decreasing dose of <10mg daily prednisone (or equivalent)
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 |
|---|---|---|
| DomatinostatAlso: 4SC-202Domatinostat is an oral tablet which will be given at a variable dose during the Phase IIA safety run in phase of the trial. During the Phase IIB efficacy phase of the trial patients will be treated with domatinostat at the safe and tolerated combination dose identified during the Phase IIA safety run in phase. | Drug | Domatinostat plus Avelumab |
| AvelumabAvelumab is a monoclonal antibody which is given via an intravenous infusion at a dose of 10mg/kg every two weeks on the first day of a two week cycle. (Day 1 q 14d) from Cycle 2 onwards. | Drug | Domatinostat plus Avelumab |
Primary outcome
Safety run-in phase: To establish a safe and tolerable dose of domatinostat in combination with avelumab for use in the main (Phase IIB efficacy) phase of the trial
Time frame: The DLT period is 28 days following the first treatment with domatinostat and avelumab
Progression through dosing levels will be determined by the occurrence of dose limiting toxicities in the study population.
Main Phase IIB (efficacy) phase: Objective response rate using RECIST 1.1 criteria
Time frame: 6 months
ORR defined as the proportion of patients with either CR or PR (assessed according to RECIST 1.1) by 6 months from combination treatment initiation. The best ORR will be presented as a proportion along side a 95% confidence interval
5 secondary outcomes
Number of patients with adverse events (according to NCI-CTCAE version 4) as a measure of safety and tolerability
Time frame: Up to 90 days after last dose
Progression free survival according to RECIST 1.1
Time frame: upto 2 years
Overall survival
Time frame: upto 2 years
Disease control rate
Time frame: At 6 and 12 months on treatment
Duration of objective response according to RECIST 1.1
Time frame: upto 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Feb 2019.
- Derived from this study: PubMed 38518549Cartwright E, Slater S, Saffery C, Tran A, Turkes F, Smith G, Aresu M, Kohoutova D, Terlizzo M, Zhitkov O, Rana I, Johnston EW, Sanna I, Smyth E, Mansoor W, Fribbens C, Rao S, Chau I, Starling N, Cunningham D. Phase II trial of domatinostat (4SC-202) in combination with avelumab in patients with previously treated advanced mismatch repair proficient oesophagogastric and colorectal adenocarcinoma: EMERGE. ESMO Open. 2024 Apr;9(4):102971. doi: 10.1016/j.esmoop.2024.102971. Epub 2024 Mar 21.
- Individual participant dataSharing planned: Undecided
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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.
David Cunningham principal investigator
Consultant Medical Oncologist
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Domatinostat and Avelumab in people with Cancer and GI Cancer, run by Royal Marsden NHS Foundation Trust at 2 sites 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 11 inclusion and 16 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: status not confirmed, as of the sponsor's last update on 5 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact David Cunningham (020 8642 6011 ext. 4480, david.cunningham@rmh.nhs.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety run-in phase: To establish a safe and tolerable dose of domatinostat in combination with avelumab for use in the main (Phase IIB efficacy) phase of the trial (time frame: The DLT period is 28 days following the first treatment with domatinostat and avelumab). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03812796, which also lists 1 linked publication.
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 5 Feb 2019.