Preoperative Nivolumab in Patients With Locally Advanced Colon Cancer (T3 or T4): a Window-of-opportunity Study (NICOLE)
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|ClinicalTrials.gov Identifier: NCT04123925|
Recruitment Status : Completed
First Posted : October 11, 2019
Last Update Posted : October 11, 2019
|Condition or disease||Intervention/treatment||Phase|
|Colon Cancer Stage II/III||Drug: Nivolumab||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||22 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Preoperative Nivolumab in Patients With Locally Advanced Colon Cancer (T3 or T4): a Window-of-opportunity Study|
|Actual Study Start Date :||June 12, 2018|
|Actual Primary Completion Date :||June 17, 2019|
|Actual Study Completion Date :||September 2, 2019|
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 at high risk
Other Name: Surgery
- Tolerability and Safety [ Time Frame: "up to 5 weeks" ]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
- Clinical Activity [ Time Frame: "presurgery" ]Objective Tumor Response Rate (ORR) as defined by Response Evaluation Criteria In Solid Tumors (RECIST)
- Predictive Biomarkers [ Time Frame: "up to 10 weeks" ]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
- Pathological Response [ Time Frame: "up to 6 weeks" ]To determine the degree of pathologic regression: percentage of patients achieving a pathological complete tumor regression (TRG1)
- Clinical efficacy [ Time Frame: 3 year ]Relapse-Free Survival Overall Survival
- Toxicities [ Time Frame: "up to 3 months" ]Postoperative complications (occurring within 60 days from surgery)
- Metabolic Response [ Time Frame: "presurgery" ]Metabolic Response by FDG-Positron emission tomography-computed tomography (PET-CT) scan prior to surgery compared to the baseline test.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04123925
|Istituto Tumori di Napoli - Fondazione G. Pascale|
|Napoli, Campania, Italy, 80131|