Colon Cancer Stage II/III Clinical Trial
— NICOLEOfficial title:
Preoperative Nivolumab in Patients With Locally Advanced Colon Cancer (T3 or T4): a Window-of-opportunity Study
| Verified date | September 2019 |
| Source | National Cancer Institute, Naples |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
A monocentric window of opportunity study preceded by a safety run-in phase. The study population will include locally advanced colon patients (T3 or T4).
| Status | Completed |
| Enrollment | 22 |
| Est. completion date | September 2, 2019 |
| Est. primary completion date | June 17, 2019 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility |
Inclusion Criteria: 1. Patients diagnosed with histologically confirmed adenocarcinoma of colon with staging of locally advanced (T3 or T4) 2. No prior treatments (chemotherapy, radiation or surgery) for colon cancer 3. Either sex aged = 18 years 4. Colon lesion determined and measured preoperatively by either spiral or multidetector CT scan 5. ECOG Performance Status =1 at study entry 6. Adequate bone marrow haematological function: absolute neutrophil count (ANC) = 1.5 x 109/L AND platelet count = 100 x 109/L AND haemoglobin = 9 g/dL 7. Adequate liver function: total bilirubin = 1.5 x upper limit of normal (ULN) AND aspartate aminotransferase (AST)/alanine aminotransferase (ALT) = 2.5 X ULN 8. Adequate renal function: serum creatinine = 1.5 mg/dL OR creatinine clearance = 60 mL/min in males and =50 mL/min in females (calculated according to Cockroft-Gault formula) 9. Serum calcium levels, international normalised ratio (INR) and partial thromboplastin time were within normal limits 10. Female subjects of childbearing potential must have a negative urine pregnancy test result at baseline and practice a reliable method of contraception throughout the study 11. Availability of tumor tissue from basal biopsy for immunoscore and biomarker analysis. 12. Ability to understand study-related patient information and provision of written informed consent for participation in the study Exclusion Criteria: 1. Evidence of metastatic disease 2. Prior malignancy within the prior 5 years. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer 3. Subjects with active, known or suspected autoimmune disease 4. Subjects with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of treatment 5. Prior treatment with an anti-PD-1, anti-Programmed Death 1 ligand (PD-L1), anti-PD-L2, or anti-cytotoxic T lymphocyte associated antigen-4 (anti- CTLA-4) antibody 6. Female subjects who are pregnant (positive urine pregnancy test), breastfeeding, or who are of childbearing potential and not practicing a reliable method of birth control 7. Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the investigator's opinion makes it undesirable for the patient to participate in the study, or which would jeopardize compliance with the protocol, or would interfere with the results of the study 8. Patients with a history of cardiovascular or interstitial lung disease and evidence or risk of retinal vein occlusion or central serous retinopathy 9. Inability to regularly access center facilities for logistical or other reasons 10. History of poor co-operation, non-compliance with medical treatment, or unreliability 11. Participation in any interventional drug or medical device study within 30 days prior to treatment start 12. Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C (HCV antibody) with virus ribonucleic acid indicating acute or chronic infection; 13. Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) |
| Country | Name | City | State |
|---|---|---|---|
| Italy | Istituto Tumori di Napoli - Fondazione G. Pascale | Napoli | Campania |
| Lead Sponsor | Collaborator |
|---|---|
| National Cancer Institute, Naples |
Italy,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Tolerability and Safety | To determine the feasibility of Nivolumab in the preoperative setting in patients with T3-T4 colon cancer: delay in surgery resection > 21 days after last administration of nivolumab; severe adverse events-NCI CTC-AE Version 4.03 criteria | "up to 5 weeks" | |
| Primary | Clinical Activity | Objective Tumor Response Rate (ORR) as defined by Response Evaluation Criteria In Solid Tumors (RECIST) | "presurgery" | |
| Primary | Predictive Biomarkers | To determine molecular and immunophenotypic changes in tumor and peripheral blood evaluating several biomarkers. Since the identification of new markers for immunotherapy is rapidly evolving, the definitive list of analyses remains to be determined | "up to 10 weeks" | |
| Secondary | Pathological Response | To determine the degree of pathologic regression: percentage of patients achieving a pathological complete tumor regression (TRG1) | "up to 6 weeks" | |
| Secondary | Clinical efficacy | Relapse-Free Survival | 3 years | |
| Secondary | Clinical efficacy | Overall Survival | 5 years | |
| Secondary | Toxicities | Postoperative complications (occurring within 60 days from surgery) | "up to 3 months" | |
| Secondary | Metabolic Response | Metabolic Response by FDG-Positron emission tomography-computed tomography (PET-CT) scan prior to surgery compared to the baseline test. | "presurgery" |