Colorectal cancer Cancer
Conditions
Interventions
Informed consent:
Patients potentially suitable for the trial will be identified at an oncology clinic, and will be approached about the trial with the aid of the patient information sheet. After disc
Sponsors
University of Birmingham
Eligibility
Sex/Gender
All
Age
18 Years to 100 Years
Inclusion criteria
Inclusion criteria: Current inclusion criteria as of 05/08/2020: 1. Histologically confirmed locally advanced or metastatic MSS CRC with class II expression (greater than 1% cancer cell positivity for class II expression on immunohistochemistry) 2. Eastern Cooperative Oncology Group (ECOG) performance status 0-2 3. Age >= 18 years 4. Patients must have completed all standard of care therapy that the treating oncologist deems appropriate. Trial treatment as first-line therapy is permitted if the patient has declined standard of care therapy 5. CT scan of chest, abdomen, pelvis within 28 days of registration demonstrating uni-dimensionally measurable disease as per RECIST version 1.1 6. Demonstrate adequate haematological function: 6.1. Platelet count > = 100 x 109 /L 6.2. Neutrophils > = 1.5 x 109/L 6.3. Haemoglobin > = 90 g/L 7. Demonstrate adequate hepatic function: 7.1. Serum bilirubin 30ml/min (as per institutional standard) 9. Provision of signed and dated, written informed consent prior to any trial-specific procedures, sampling and analyses. 10. Negative pregnancy test (female patients of reproductive potential) 11. Patients must agree to the use of contraception Previous inclusion criteria: 1. Histologically confirmed locally advanced or metastatic MSS CRC with strong class II expression (greater than 50% cancer cell positivity for class II expression on immunohistochemistry) 2. Eastern Cooperative Oncology Group (ECOG) performance status 0-2 3. Age > = 18 years 4. Patients must have completed all standard of care therapy that the treating oncologist deems appropriate. Trial treatment as first-line therapy is permitted if the patient has declined standard of care therapy 5. CT scan of chest, abdomen, pelvis within 28 days of registration demonstrating uni-dimensionally measurable disease as per RECIST version 1.1 6. Demonstrate adequate haematological function: 6.1. Platelet count > = 100 x 109 /L 6.2. Neutrophils > = 1.5 x 109/L 6.3. Haemoglobin > = 90 g/L 7. Demonstrate adequate hepatic function: 7.1. Serum bilirubin 30ml/min (as per institutional standard) 9. Provision of signed and dated, written informed consent prior to any trial-specific procedures, sampling and analyses. 10. Negative pregnancy test (female patients of reproductive potential) 11. Patients must agree to the use of contraception
Exclusion criteria
Exclusion criteria: 1. Previous treatment with PD1/PDL1 inhibitors 2. Untreated symptomatic brain or leptomeningeal metastatic disease 3. Medical or psychiatric conditions compromising informed consent 4. Any medical condition which, in the opinion of the Investigator, would compromise the ability of the patient to participate in the trial or which would jeopardise compliance with the protocol 5. Administration of chemotherapy, radioactive or biological cancer therapy within 4 weeks prior to the first dose of trial therapy 6. Patient has not recovered to CTCAE grade 1 or better from the Adverse Event (AE) due to cancer therapeutics administered more than 4 weeks earlier 7. Active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment 8. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment 9. Patient has risk factors for bowel obstruction or bowel perforation (examples include but not limited to a history of acute diverticulitis, intra-abdominal abscess and abdominal carcinomatosis) 10. Patient has a known history of other malignancy, unless the patient has undergone potentially curative therapy with no evidence of that disease for 3 years 11. Has a history of non-infectious pneumonitis requiring steroids or has active pneumonitis or significantly reduced transfer coefficient (KCO) 12. Female patients that are either pregnant or breastfeeding 13. Male and female patients (of childbearing age) not willing to use adequate contraception 14. Patient previously had a severe hypersensitivity reaction to treatment with another monoclonal antibody 15. Patient is positive for Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies), active Hepatitis B (HBsAg reactive) or Hepatitis C (HCV RNA (qualitative) is detected); patients with negative Hepatitis C antibody testing may not need RNA testing 16. Known history of tuberculosis 17. Patient has an active infection requiring therapy 18. Has received a live vaccine within 30 days prior to the first dose of trial treatment 19. Patient is, at the time of signing informed consent, a regular user (including “recreational use”) of any illicit drugs or had a recent history (within the last year) of substance abuse (including alcohol)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Durable clinical benefit (DCB) defined as the occurrence of complete response (CR), partial response (PR) or stable disease (SD) for 27 weeks or greater | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Objective response: overall tumour burden assessed using RECIST version at CT scans every 9 weeks from trial entry up to 45 weeks, then every 12 weeks, until disease progression 2. Best percentage change in sum of target lesion diameters - at each evaluation, the longest diameters of all selected target lesions will be measured and summed and the percentage change from the baseline measurement will be calculated. The best percentage change is the one that reflects either the greatest decrease or the least increase over the whole period of assessment. 3. Time to maximal response, defined as the time from commencement of trial treatment to the date of CT scan that first records the best objective response as per RECIST 4. Progression-free survival time, defined as the time from commencement of trial treatment to the date of CT scan when progressive disease first recorded or date of death without previously recorded progression 5, Overall survival time, defined as the time from commencement of trial treatment to the date of death | — |
Countries
England, Northern Ireland, Scotland, United Kingdom
Outcome results
None listed