Preoperative Nivolumab in Patients With Locally Advanced Colon Cancer (T3 or T4): a Window-of-opportunity Study

• Status: Completed
• Trial end date: 2019-09-02
• Target enrollment: 0
• Participant gender: All

Summary

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).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Cancer Institute, Naples
• Treatments: Nivolumab

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

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)