NCT04123925

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

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 22 (actual)
• Sponsor: National Cancer Institute, Naples · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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).

Detailed description

An initial 6-patients safety run-in cohort will be followed by an expansion cohort, with a planned accrual of 16 patients. 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. 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. 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). Additional correlative biological studies will be performed for the evaluation of the biomarkers indicated above on the biological samples (paraffin-embedded tissue, frozen tissue, blood, serum, etc.). Biomarkers will be evaluated on tumor tissues obtained by biopsies at baseline, and by surgery after neoadjuvant treatment. A comparison with a subsequent cohort of 22 patients with locally advanced colon cancer (T3-T4) who proceed to surgical resection without preoperative anti-PD-1 and recruited following the end of the enrollemnt of the planned pateints in the Nicole study, will be performed. Blood samples will be collected at baseline, prior to surgery, and at the recurrence of the disease (progressive disease \[PD\]). Biomarkers will be correlated with pathological response and patient's outcome. Patients will have follow-up evaluation every six months for five years.

Conditions

• Colon Cancer Stage II/III

Interventions

Type	Name	Description
DRUG	Nivolumab	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

Timeline

• Start date: 2018-06-12
• Primary completion: 2019-06-17
• Completion: 2019-09-02
• First posted: 2019-10-11
• Last updated: 2020-06-12

Locations

1 site across 1 country: Italy