Pre-operative immunotherapy in early-stage colon cancers
- Conditions
- stage 2-3 adenocarcinoma of the colonMedDRA version: 20.0Level: LLTClassification code 10009957Term: Colon carcinomaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-002940-17-NL
- Lead Sponsor
- Antoni van Leeuwenhoek
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 155
Study population. In order to be eligible to participate in this study, a subject must meet all of the following criteria:
• Stage 2-3 (>T3 and/or N+) adenocarcinoma of the colon (and rectosigmoid considered as non-rectal and not undergoing neoadjuvant treatment) for the MSI cohort;
- No signs of distant metastases on CT-scan and physical examination;
- No clinical obstruction;
- No clinical symptoms or radiological suspicion of perforation;
• Colonoscopy must be performed after registration to obtain study-specific biopsies. If biopsies are not possible, patients cannot be included in the study;
• WHO performance status of 0 or 1;
• Screening laboratory tests must meet the following criteria and should be obtained within 7 days prior to randomization/registration: WBC > 2.0 x 10^9/L, ANC > 1.5x10^9/L, platelets > 100 x 10^9/L, Hemoglobin > 5.0mmol/L. Transfusion is allowed to obtain an adequate hemoglobin level. Liver function tests: total bilirubin < 1.5 upper limit of normal (ULN) (except for subjects with Gilbert syndrome, who can have total bilirubin <3.0 mg/dL); alkaline phosphatase <2.5 ULN; transaminases (ASAT/ALAT) <3 x ULN; LDH < 2 x ULN;
• Creatinine clearance (Cockcroft-Gault) of >40 ml/min;
• Women of childbearing potential (WOCBP)* must use appropriate method(s) of contraception. WOCBP should use an adequate method to avoid pregnancy for 23 weeks (30 days plus the time required for nivolumab to undergo five half-lives) after the last dose of investigational drug;
• Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of nivolumab;
• Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year. Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 31 weeks after the last dose of investigational product. Women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile as well as azoospermic men do not require contraception;
• CT-scan must be performed within 28 days prior to registration;
• No previous treatment with immune checkpoint inhibitors targeting including but not limited to CTLA-4, PD-1 or PD-L1;
• No previous treatment with chemotherapy;
- No radiotherapy prior to or planned post-surgery radiotherapy;
- Allergies and Adverse Drug Reaction:
No history of allergy to study drug components
No history of severe hypersensitivity reaction to any monoclonal antibody
- No intercurrent illnesses, including but not limited to infections, unstable angina pectoris
- No underlying medical conditions that, in the Investigator’s opinion, will make the administration of the study drug hazardous or obscure the interpretation of toxicity determination of adverse events;
- No positive test for hepatitis B virus surface antigen (HBsAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection;
- No history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS);
- No active autoimmune disease or a documented history of autoimmune disease, or other medical conditions requiring systemic steroid or immunosuppressive medications, except for subjects with vitiligo, diabetes mellitus type 1, residual hypothyroidism due to autoimmune condition only requiring hormone replac
Study population. In order to be eligible to participate in this study, a subject must meet all of the following criteria:
• Stage 2-3 (>T3 and/or N+) adenocarcinoma of the colon (and rectosigmoid considered as non-rectal and not undergoing neoadjuvant treatment) for the MSI cohort;
- No signs of distant metastases on CT-scan and physical examination;
- No clinical obstruction;
- No clinical symptoms or radiological suspicion of perforation;
• Colonoscopy must be performed after registration to obtain study-specific biopsies. If biopsies are not possible, patients cannot be included in the study;
• WHO performance status of 0 or 1;
• Screening laboratory tests must meet the following criteria and should be obtained within 7 days prior to randomization/registration: WBC > 2.0 x 10^9/L, ANC > 1.5x10^9/L, platelets > 100 x 10^9/L, Hemoglobin > 5.0mmol/L. Transfusion is allowed to obtain an adequate hemoglobin level. Liver function tests: total bilirubin < 1.5 upper limit of normal (ULN) (except for subjects with Gilbert syndrome, who can have total bilirubin <3.0 mg/dL); alkaline phosphatase <2.5 ULN; transaminases (ASAT/ALAT) <3 x ULN; LDH < 2 x ULN;
• Creatinine clearance (Cockcroft-Gault) of >40 ml/min;
• Women of childbearing potential (WOCBP)* must use appropriate method(s) of contraception. WOCBP should use an adequate method to avoid pregnancy for 23 weeks (30 days plus the time required for nivolumab to undergo five half-lives) after the last dose of investigational drug;
• Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of nivolumab;
• Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year. Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 31 weeks after the last dose of investigational product. Women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile as well as azoospermic men do not require contraception;
• CT-scan must be performed within 28 days prior to registration;
• No previous treatment with immune checkpoint inhibitors targeting including but not limited to CTLA-4, PD-1 or PD-L1;
• No previous treatment with chemotherapy;
- No radiotherapy prior to or planned post-surgery radiotherapy;
- Allergies and Adverse Drug Reaction:
No history of allergy to study drug components
No history of severe hypersensitivity reaction to any monoclonal antibody
- No intercurrent illnesses, including but not limited to infections, unstable angina pectoris
- No underlying medical conditions that, in the Investigator’s opinion, will make the administration of the study drug hazardous or obscure the interpretation of toxicity determination of adverse events;
- No positive test for hepatitis B virus surface antigen (HBsAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection;
- No history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS);
- No active autoimmune disease or a documented history of autoimmune disease, or other medical conditions requiring systemic steroid or immunosuppressive medications, except for subjects with vitiligo, diabetes mellitus type 1, residual hypothyroidism due to autoimmune condition only requiring hormone replac
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method