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

NCT04123925 | Completed Phase 2

• 1 other identifier: NICOLE
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Colon Cancer Stage II/III

Keywords

locally advanced colon; neoadjuvant; nivolumab

Outcome Measures

Primary Outcomes (3)

• 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"

• Clinical Activity

  Objective Tumor Response Rate (ORR) as defined by Response Evaluation Criteria In Solid Tumors (RECIST)

  "presurgery"

• 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 Outcomes (5)

• Pathological Response

  "up to 6 weeks"

• Clinical efficacy

  3 years

• Clinical efficacy

  5 years

• Toxicities

  "up to 3 months"

• Metabolic Response

  "presurgery"

Study Arms (1)

Nivolumab

EXPERIMENTAL

Patients will receive nivolumab at a flat dosage of 240 mg every two weeks on Day -28 and Day-14 (+/- one day) prior to planned surgery on Day 0 or up to +7 days

Drug: Nivolumab

Interventions

Nivolumab DRUG

Locally advanced colon cancer must be documented at screening (within 21 days prior to initiation of study treatment) and re-assessed prior surgery by spiral or multidetector computed tomography (CT) scan Postoperatively, standard adjuvant chemotherapy will be administered in pathological III-stage and at investigator discretion in pathological II-stage at high risk

Also known as: Surgery

Nivolumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients diagnosed with histologically confirmed adenocarcinoma of colon with staging of locally advanced (T3 or T4)
• No prior treatments (chemotherapy, radiation or surgery) for colon cancer
• Either sex aged ≥ 18 years
• Colon lesion determined and measured preoperatively by either spiral or multidetector CT scan
• ECOG Performance Status ≤1 at study entry
• 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
• Adequate liver function: total bilirubin ≤ 1.5 x upper limit of normal (ULN) AND aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 2.5 X ULN
• 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)
• Serum calcium levels, international normalised ratio (INR) and partial thromboplastin time were within normal limits
• 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
• Availability of tumor tissue from basal biopsy for immunoscore and biomarker analysis.
• Ability to understand study-related patient information and provision of written informed consent for participation in the study

You may not qualify if:

• Evidence of metastatic disease
• 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
• Subjects with active, known or suspected autoimmune disease
• Subjects with a condition requiring systemic treatment with either corticosteroids (\>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of treatment
• 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
• 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
• 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
• Patients with a history of cardiovascular or interstitial lung disease and evidence or risk of retinal vein occlusion or central serous retinopathy
• Inability to regularly access center facilities for logistical or other reasons
• History of poor co-operation, non-compliance with medical treatment, or unreliability
• Participation in any interventional drug or medical device study within 30 days prior to treatment start
• Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C (HCV antibody) with virus ribonucleic acid indicating acute or chronic infection;
• Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)

Sponsors & Collaborators

• National Cancer Institute, Naples: lead

Study Sites (1)

Istituto Tumori di Napoli - Fondazione G. Pascale

Napoli, Campania, 80131, Italy

Location

MeSH Terms

Interventions

Nivolumab; Surgical Procedures, Operative

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 4, 2019
• First Posted: October 11, 2019
• Study Start: June 12, 2018
• Primary Completion: June 17, 2019
• Study Completion: September 2, 2019
• Last Updated: June 12, 2020

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)