EMERGE is a trial to investigate whether combining the histone deacetylase inhibitor (HDAC inhibitor) drug 4SC-202 with the immunotherapy drug avelumab is safe and improves outcomes for patients with previously treated gastroesophageal or colorectal cancer

Phase 1

Active, not recruiting

• Conditions: Advanced gastrooesophageal and colorectal cancer; MedDRA version: 20.0Level: PTClassification code 10009944Term: Colon cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: LLTClassification code 10042080Term: Stomach cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.0Level: PTClassification code 10030137Term: Oesophageal adenocarcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2017-001770-42-GB
• Lead Sponsor: The Royal Marsden NHS Foundation Trust

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2018-03-22
• Last Update Posted: 6 July 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 83

Inclusion Criteria

i.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.
vii.Adequate bone marrow function:
a.Absolute neutrophil count (ANC) =1.5 x109/L
b.White blood count >3x109/L
c.Platelets =100x109/L
d.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.
ix.Adequate liver function
a.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
a.International Normalised Ratio (INR) < 1.5
b.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.
xv.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 3 monthsafter 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 3 months after the last dose of trial treatment. 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.
xvii) Measurable disease

Exclusion Criteria

Patients are not eligible for the trial if any of the exclusion criteria below are met:
i.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.
iv.All subjects with brain metastases, except those meeting the following criteria:
a.Brain metastases that have been treated locally and are clinically stable for at least 2 weeks prior to enrolment
b.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)
c.Subjects must be either off steroids or on a stable or decreasing dose of <10mg daily prednisone (or equivalent)
v.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.
vii.Any immunodeficiency disorder
viii.Any active, known or suspected autoimmune disease that might deteriorate when receiving immunostimulatory agent, with the following exceptions:
a.Patients with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible
b.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
c.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.
ix.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:
a. Myocardial infarction within the previous 6 months
b. Unstable angina
c. Congestive heart failure =NYHA Classification Class II
d. Serious cardiac arrhythmia requiring medication (for example,
ventricular tachycardia, supraventricular tachycardia or atrial fibrillation with a resting heart rate > 110bpm)
e. Patients with a marked baseline prolongation of QT/QTc interval, e.g., repeated demonstration of a QTc interval >450 msec (Grade 1 NCI-CTCAE); Long-QT-Syndrome (QTcF is applicable)
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.
xvi.Major surgery, major trauma or open biopsy within 28 days prior to registration (not including staging laparoscopy)
xvii.Evidence of bleeding diathesis or

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified