PALEO: This study is investigating the effectiveness of a radiotherapy, immunotherapy and chemotherapy treatment regimen in people with oesophageal cancer that has spread to another area of the bodyPhase II clinical trial of chemoradioimmunotherapy for the ALleviation of oEsOphageal cancer complications

Exclusion

1. Bulky or organ-threatening metastatic disease requiring upfront higher dose chemotherapy in the judgement of the treating clinician.
2. Known tumour HER2 positivity (IHC 2+ or more and HER2 gene amplification on in situ hybridisation)
3. Previous systemic therapy for oesophageal or GOJ carcinoma.
4. Previous thoracic radiotherapy. Prior palliative radiotherapy to bony metastases is permitted.
5. Oesophageal stent in situ.
6. Known tracheo-oesophageal fistula.
7. Leptomeningeal or uncontrolled brain metastases. Controlled brain metastases are those which have been treated and are radiologically and/or clinically stable, and the patient is asymptomatic and does not require steroids.
8. Major surgical procedure (as defined by the Investigator) within 28 days prior to first day of study treatment. Note: Local surgery of isolated lesions for palliative intent is permitted.
9. History of another malignancy within the last 3 years, with the exception of adequately treated non-melanomatous skin cancer, carcinoma in situ and superficial transitional cell carcinoma of the bladder.
10. Prior therapy with an anti-PD1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T cell co-stimulation or immune checkpoint pathways.
11. Sensory neuropathy of grade 2 or higher severity per CTCAE v5.0
12. History of allergy or hypersensitivity to study drug components, or other contraindications to any of the study drugs. Active or prior documented autoimmune disorders (including inflammatory bowel disease [e.g., ulcerative colitis or Crohn's disease], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis], Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc). Patients with the following conditions are exceptions to this criterion:
a. Vitiligo or alopecia.
b. Hypothyroidism (e.g., following Hashimoto syndrome) stable on thyroid hormone replacement.
c. Any chronic skin condition (e.g. psoriasis) that does not require systemic therapy.
d. Type 1 diabetes mellitus.
e. Coeliac disease controlled by diet alone.
13. Patients without active autoimmune disease in the last 5 years may also be included but only after consultation with the Chief Principal Investigators.Any condition requiring continuous systemic treatment with either regular corticosteroids (>10mg daily prednisone or equivalent dose of an alternative corticosteroid) or other immunosuppressive medications within 14 days of study drug administration. Intranasal, inhaled or topical steroids, and adrenal replacement steroid doses >10mg daily oral prednisone equivalent, are permitted in the absence of active autoimmune disease.
14. Positive test for hepatitis B surface antigen (HBsAg) indicating acute or chronic infection. Participants with a past or resolved HBV infection (defined as the presence of anti-HBc and absence of HBsAg) are eligible.
15. Positive test for hepatitis C virus antibody (HCV antibody) , unless polymerase chain reaction is negative for HCV RNA.
16. History of other significant, or active, infection, including HIV or tuberculosis (TB). HIV testing is not mandatory unless clinically indicated. Clinical evaluation for active TB may include clinical history, physical examination and radiographic findings, or tuberculosis testing in line with local practice.
17. Receipt of a transplanted solid organ (kidney, liver, heart or lung) or of an allogeneic bone marrow transplant.
18. Receipt of a live attenuated vaccine within 30 days prior to registration.
19. Use of alternative or traditional medicines within 14 days prior to registration.
20. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring adverse events or compromise the ability of the patient to give written informed consent.
21. Pregnancy, lactation, or inadequate contraception. Women must be post-menopausal, infertile, or use a reliable means of contraception to avoid pregnancy for 90 days after the last dose of durvalumab. Women of childbearing potential must have a negative pregnancy test within 24 hours prior to trial registration. Men must have been surgically sterilized or use a double barrier method of contraception if they are sexually active with a woman of childbearing potential for a period of 180 days after the last dose of durvalumab and chemotherapy, or 90 days after the last dose of durvalumab monotherapy (whichever is the longer time period). Sperm donation is not permitted for 180 days after the last dose of durvalumab and chemotherapy, or 90 days after the last dose of durvalumab monotherapy (whichever is the longer time period).