colon cancer: a window-of-opportunity study MedDRA version: 20.0 Level: PT Classification code 10009944 Term: Colon cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classification code 10009944 Term: Colon cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: LLT Classification code 10009989 Term: Colonic cancer System Organ Cl
Conditions
Interventions
Trade Name: OPDIVO - 10 MG/ML- CONCENTRATO PER SOLUZIONE PER INFUSIONE- USO ENDOVENOSO- FLACONCINO (VETRO)- 10 ML- 1 FLACONCINO
Product Name: nivolumab
Product Code: BMS-936558
Pharmaceutical Form: S
Sponsors
SOCIETà CAMPANA DI IMMUNOTERAPIA ONCOLOGICA
Eligibility
Sex/Gender
All
Inclusion criteria
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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 11 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 11
Exclusion criteria
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), breast-feeding, 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)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: o 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. -To determine the degree of pathologic regression: percentage of patients achieving a pathological complete tumor regression (TRG1). -To determine molecular and immunophenotypic changes in tumor and peripheral blood evaluating several biomarkers. ;Secondary Objective: ¿Objective Tumor Response Rate (ORR) as defined by Response Evaluation Criteria In Solid Tumors (RECIST) ¿Metabolic Response by FDG-Positron emission tomography¿computed tomography (PET-CT) scan prior to surgery compared to the baseline test. ¿Postoperative complications (occurring within 60 days from surgery) ¿Relapse-Free Survival ¿Overall Survival;Primary end point(s): Safety Assessments Efficacy Assessments Biomarker study;Timepoint(s) of evaluation of this end point: Safety Assessments: Toxicities will be evaluated throughout the study treatment and up to 30 days after surgery. Toxicity will be graded according to the NCI Common Toxicity Criteria. The National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTC-AE) Version 4.03 will be used to evaluate the clinical safety of the treatment in this study. Patients will be assessed for AEs at each clinical visit and as necessary throughout the study. Grade =3 hematological and non-hematological toxicities will be recorded. Efficacy Assessments: Pathological tumor regression will be evaluated according to Mandard modified scoring system [Mandard 1994]. Biomarker study: The Immunoscore evaluation will be assessed using standardized Immunoscore assays and software (HalioDx). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The clinical response is a secondary objective of the study and will be evaluated through repetition of either spiral or multidetector CT scan prior to surgery (within 3 days before surgery) and defined according to the RECIST (Response Evaluation Criteria In Solid Tumours) guidelines version 1.1.; Metabolic response evaluated by FDG-PET is a secondary objective. Therefore PET-CT scans are planned at baseline (before treatment) and prior to surgery (within 3 days before surgery).; Postoperative complications; Relapse-Free Survival; Overall Survival;Timepoint(s) of evaluation of this end point: within 3 days before surgery (7 weeks after signing the consent); Metabolic response evaluated by FDG-PET is a secondary objective. Therefore PET-CT scans are planned at baseline (before treatment) and prior to surgery (within 3 days before surgery).; 60 days from surgery; Patients will have follow-up evaluation every six months for five years.; Patients will have follow-up evaluation every six months for five years. | — |
Countries
Italy
Contacts
Public ContactCRO
Clinical Research Technology Srl
Outcome results
None listed