Ave-Rec study: This phase II trial is evaluating the addition of an immunotherapy drug following long-course chemo-radiotherapy in patients with a locally advanced rectal cancer that is able to be surgically removedPhase II Trial PD-L1/PD-1 Blockade Avelumab (MSB0010718C) With Chemoradiotherapy for Locally Advanced ResectableT3b-4/N1-2 Rectal Cancer

Exclusion

1. Patients with disease outside the pelvis
2. Prior pelvic radiotherapy
3. Participation in another interventional clinical trial within 30 days of registration (participation in observational studies are permitted)
4. Concurrent anti-cancer treatment
5. Concurrent treatment with a non-permitted drug (Section 8.3.2)
6. Major surgery for any reason within 4 weeks of registration (except defunctioning stoma creation with the patient having fully recovered from this procedure)

7. Current use of immunosuppressive medication. Except for the following: (a) intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); (b). Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent; (c). Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication); (d) Short-term administration of systemic steroids (that is, for allergic reactions or the management of irAEs) is allowed while on study.

   Note: Patients receiving bisphosphonate or denosumab are eligible

8. Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible
9. Active or history of immunodeficiencies
10. Has received prior therapy with an anti-PD1, anti-PDL1, anti-PDL2 or anti-CTLA-4 agents
11. Has clinically significant (that is, active) cardiovascular disease: cerebral vascular accident / stroke (< 6 months prior to registration), myocardial infarction (< 6 months prior to registration), unstable angina, congestive heart failure (New York Heart Association Classification Class ≥ II), or serious cardiac arrhythmia requiring medication.
12. Has an active infection requiring systemic therapy
13. Other severe acute or chronic medical conditions including immune colitis, inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis 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
14. Prior malignancies within 3 years of registration (with the exception of non- melanomatous skin cancer)
15. Prior organ transplantation, including allogeneic stem-cell transplantation
16. A known history of testing positive for HIV or known acquired immunodeficiency syndrome (AIDS)
17. Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test is positive)
18. Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (CTCAE v4.03 grade ≥ 3)
19. Is pregnant or lactating
20. Vaccination within 4 weeks of registration and while on trials is prohibited except for administration of inactivated vaccines
21. Known deficiency of dihydropyrimidine dehydrogenase