This is an open-label, single-arm phase II study. Patients will receive standard dose
      single-agent ibrutinib delivered orally at a dose of 560mg once daily continuously on a 4
      weekly cycle until disease progression or unacceptable toxicity occurs.

      Single arm, open label means that both researchers and participants know the treatment which
      is being administered, and all participants in the trial will receive the study drug
      ibrutinib.

      A Phase 2 study was chosen as more information about the efficacy and toxicity of this drug
      in this specific group of patients is needed prior to considering a larger phase 3 study.

      Eligible patients are those with advanced unresectable or metastatic oesophagogastric
      adenocarcinoma or squamous cell carcinoma who have been treated with at least 1 prior
      chemotherapy for advanced or metastatic disease. In the case of HER2 positive tumours,
      previous treatment with chemotherapy with or without a HER2 targeted agent is allowed.

      There will be a two step enrollment process:

        1. Enrollment for prescreening to establish cMYC and HER2 status (which may occur during
           1st line treatment or after progression on 1st line treatment)

        2. Enrollment for randomisation and treatment The patient will first be given the
           prescreening participant information sheet (PIS) and informed consent form (ICF) that
           has been approved by the Ethics Committee. They will have the study explained to them
           and be given the opportunity to ask questions. If they agree to take part, they will be
           asked to sign the approved consent form, and they will keep a copy of the signed consent
           form.

           Prescreening If a participant agrees to take part in the prescreening for the study a
           previously obtained sample of their cancer (usually a diagnostic biopsy) will be taken
           out of storage and sent to the trial laboratory where the tissue will be tested for both
           cMYC and HER2 amplification. If there is no archival tumour sample available or if the
           existing tumour sample is of insufficient quality, the patient will be given the option
           to consent to a pre-screening biopsy to obtain a fresh sample.

           A blood test will be taken for plasma DNA analysis including circulating tumour cell
           number, c-MYC copy number variation (by digital droplet PCR) and blood-borne biomarkers.
           It can take up to 4 weeks to get these results which is why we will try to pre-screen
           patients to avoid delays in treatment. When the patient's disease progresses on 1st line
           treatment and if they are a suitable candidate for second line treatment their team will
           confirm if there are spaces available on study according to the the patients cMYC and
           HER2 status.

           If there are spaces available they will be given the main study PIS and ICF that has
           been approved by the Ethics Committee. They will have the study explained to them and be
           given the opportunity to ask questions. If they agree to take part, they will be asked
           to sign the approved consent form, and they will keep a copy of the signed consent form

           Screening

           If a participant agrees to take part in the main study, assessments will be made to make
           sure that he/she is eligible for the study. Some of these assessments may already have
           been done as part of the participant's standard of care, in which case, the results of
           those tests may be used. The assessments that will be done are described below:

           Disease status Tumour sample details, c-MYC and HER2 status if re-tested
           Medical/surgical history Pregnancy testing for female patients World Health Organisation
           (ECOG) performance status Physical examination to assess all conditions that are current
           and ongoing. Vital signs: height, weight, pulse, systolic blood pressure and diastolic
           blood pressure ECG Tumour biopsy* Tumour assessments (RECIST v1.1), consisting of either
           staging CT or MRI imaging FDG-PET scan* Concomitant medication. Adverse events Blood
           tests for clinical biochemistry and haematology Urinalysis Blood tests for DNA analysis
           including Circulating Tumor Cell (CTC) number, c-MYC copy number variation (by digital
           droplet PCR) and bloodborne biomarker analysis*

           *These procedures will only be carried out once all other criteria for trial entry are
           met.

           If the results of screening tests confirm that the patient can take part in the study
           they will be asked to return to the clinic to see their doctor for assessments as
           detailed below during the study treatment period.

           Study treatment period During the treatment period the patient will be seen regularly in
           clinic.The treatment is oral capsules given once per day every day in cycles lasting 28
           days. Patients will be seen on day 1, 8 and 15 of the first cycle of treatment and then
           on day 1 of every cycle (every four weeks) for the remainder of the study duration. When
           they stop being treated within the study they will have a 30 day follow up visit and
           then be followed up every 8 weeks, although this contact can be over the telephone.

           Before each treatment cycle, the patient will be examined and have safety blood tests to
           make sure that it is safe to proceed with treatment as mentioned below. Patients will
           have different procedures done at different times during the study treatment period
           including:

           Measurement of resting blood pressure and pulse rate before every treatment (at all
           study visits).

           Physical examination at the beginning of each cycle (every four weeks). Documentation of
           any changes in the medication taken and whether the patient has had any problems or
           discomfort since the last visit (at all study visits).

           An ECG at baseline and on completion of study, and at any further timepoint if
           clinically indicated Blood samples to check haematology and clinical chemistry results
           (every 4 weeks or if clinically indicated) Blood samples for plasma DNA analysis
           including CTC number, c-MYC copy number variation (by ddPCR) and bloodborne biomarker
           analysis. These will be taken on cycle 1 day 15, cycle 3 day 1 and then every 8 weeks
           (alternate cycles).

           Blood samples to assess pharmacokinetics of ibrutinib on cycle 1 day 8 (predose, 2
           hours, 6 hours post dose) and one further sample on cycle 1 day 15.

           Assessment of the status of disease using CT or MRI imaging at week 8 and then every 8
           weeks.

           Assessment with PET CT scan at baseline, day 14 and week 8 to correlate with tumour
           response and genetic changes seen Health related quality of life questionaires for the
           patient to fill out at the beginning of each cycle (every 4 weeks)

           As mentioned above, a biopsy at the time of screening is mandatory for entry into the
           trial. As part of the trial further optional biopsies will be offered to the patient:

           at day 14 (in all patients on ibrutinib) at week 8 (on those patients responding to
           ibrutinib) on discontinuation of study treatment (on those patients who have progressed
           on ibrutinib)

           Treatment discontinuation visit:

           When the patient withdraws from the study or treatment is permanently discontinued, they
           will need to attend the clinic for a visit and the following assessments will be carried
           out:

           Changes in the medication taken and any problems or discomfort since their last visit
           will be documented.

           If the patient has a side effect at their final study visit or withdrawal visit then the
           study doctor may wish to contact them and ask about it, until it has completely
           resolved. The study sponsor may also ask the study doctor for this information.

           When the patient has completed the study, the doctor will then decide whether they
           require further treatment outside the study. They will continue to be followed up within
           the study every 8 weeks to document what other cancer treatment they may or may not be
           taking and to document overall survival. This contact may be in clinic if they are
           attending the hospital or can be by telephone if they are not.

           Timeline for Final Report The study is planned to recruit over 24 months with a further
           12 months of follow up with final report planned for within 12 months of the last
           patient's last visit.