Colon cancer stage III MedDRA version: 20.0 Level: LLT Classification code 10009949 Term: Colon cancer Duke's C System Organ Class: 100000004864
Conditions
Interventions
Product Name: Avelumab
Product Code: MSB0010718C
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Avelumab
CAS Number: 1537032-82
Current Sponsor code: MSB0010718C
Conce
Sponsors
The Royal Marsden NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female subjects aged =18 years 2. ECOG PS 0/1 3. Histologically proven, stage III (i.e., any T, N1 or N2, M0) adenocarcinoma of the colon (as defined by the presence of the inferior pole of the tumour above the peritoneal reflection - that is, at least 15 cm from the anal margin). 4. Fully surgically resected tumour with clear resection margins (i.e., >1 mm) 5. Locally confirmed defective mismatch repair (dMMR) tumour (as defined by the lack of staining on either the pre-operative biopsy samples or resection specimens of at least one of the following proteins: MLH1, MSH2, MSH6, PMS2) or centrally confirmed POLE exonuclease domain mutated tumour (in subjects =65 years) yes F.1.3.1 Number of subjects for this age range 100
Exclusion criteria
Exclusion criteria: 1. Rectal tumours (as defined by the presence of the inferior pole of the tumour below the peritoneal reflection - that is, 1 NCI-CTCAE v4.0; however, alopecia and sensory neuropathy Grade =2 is acceptable unless oxaliplatin administration is planned as part of the adjuvant treatment 9. Pregnancy or lactation 10. Known alcohol or drug abuse 11. Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (<6 months prior to enrollment), myocardial infarction (<6 months prior to enrollment), unstable angina, congestive heart failure (= New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication 12. Known history of colitis, pneumonitis and pulmonary fibrosis (for example, inflammatory bowel disease, uncontrolled asthma), which, in the opinion of the Investigator, might impair the subject’s tolerance of trial treatment. 13. Any psychiatric condition that would prohibit the understanding or rendering of informed consent 14. Vaccination within 4 weeks of the first dose of Avelumab and while on trial is prohibited except for administration of inactivated vaccines 15. Other invasive malignancy within 2 years except for non-invasive malignancies such as cervical carcinoma in situ, non-melanomatous carcinoma of the skin or ductal carcinoma in situ of the breast that has/have been surgically cured. Cancer subjects with incidental histological findings of prostate cancer (tumour/node/metastasis stage of T1a or T1b or prostate-specific antigen ?10) who have not received hormonal treatment may be included, pending a discussion with the study physician.
Design outcomes
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Median DFS • Overall survival • Median OS • Adverse events • HRQoL • Quality Adjusted Life Years (QALYs) • Health Resource Use ;Timepoint(s) of evaluation of this end point: - Median DFS will be evaluated at the same time of 3-year DFS and at the end of the trial - Overall survival will be evaluated at 5 and 7 years - Median OS will be evaluated at the same time of Overall survival (see above) - Adverse events will be evaluated once all patients have completed treatment and at the end of the study - HRQoL will be evaluated at the end of the study - Quality Adjusted Life Years (QALYs) will be evaluated at the end of the study - Health Resource Use will be evaluated at the end of the study | — |
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The purpose of this study is to determine if dMMR/or POLE exonuclease domain mutant stage III colon cancer patients gain clinical benefit (i.e. reduction of the risk of cancer coming back) from the PD-L1 inhibitor Avelumab in combination with standard adjuvant chemotherapy after surgical removal of the tumour.;Secondary Objective: Does the combination of surgery, adjuvant chemotherapy and Avelumab increase the overall survival compared to surgery and adjuvant chemotherapy alone? Is the combination of surgery, adjuvant chemotherapy and Avelumab acceptable in terms of adverse events compared to surgery and adjuvant chemotherapy alone? Does the combination of surgery, adjuvant chemotherapy and Avelumab improve patients' quality of life compared to surgery and adjuvant chemotherapy alone? Is the combination of surgery, adjuvant chemotherapy and Avelumab cost-effective compared to surgery and adjuvant chemotherapy alone?;Primary end point(s): The primary endpoint is DFS at 3 years. ;Timepoint(s) of evaluation of this end point: The main analysis will take place once 60 events have occurred. DFS at 3 years is defined as the proportion of subjects who are alive and disease-free at 3 years. For subjects who neither progressed nor died, their DFS time will be censored at the last date of contact. Relapse will be based on RECIST (v 1.1) criteria. Where a patient has neither progressed nor died, their DFS time will be censored at the last date of contact (known to be alive and relapse free). | — |
Countries
United Kingdom
Contacts
Public ContactAngela Gillbanks
Royal Marsden Hospital
Outcome results
None listed