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Colon Cancer Stage II/IIIPhase 2NICOLENCT04123925

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

A Phase 2 study testing Nivolumab in people with Colon Cancer Stage II/III, run by National Cancer Institute, Naples at 1 site in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Colon Cancer Stage II/III
What is being tested?
Nivolumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
22 participants
Where
1 siteItaly
Study dates
12 Jun 2018to 2 Sep 2019
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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)

Trial locations and contacts

1 site in 1 country.

Italy1 site

  • Istituto Tumori di Napoli - Fondazione G. Pascale

    Naples, Campania, 80131

Other trials in Italy

About this study

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).

Read the 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.

Being tested
Nivolumab
Keywords
locally advanced colon, neoadjuvant, nivolumab

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NivolumabDrug

    Also called Surgery

    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

Study groups in NCT04123925
Study groupRoleWhat they receive
NivolumabExperimentalPatients 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
Receives: Drug: Nivolumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: "up to 5 weeks"

  2. Clinical Activity

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

    Measured: "presurgery"

  3. 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

    Measured: "up to 10 weeks"

Secondary outcomes (5)

  1. Pathological Response

    To determine the degree of pathologic regression: percentage of patients achieving a pathological complete tumor regression (TRG1)

    Measured: "up to 6 weeks"

  2. Clinical efficacy

    Relapse-Free Survival

    Measured: 3 years

  3. Clinical efficacy

    Overall Survival

    Measured: 5 years

  4. Toxicities

    Postoperative complications (occurring within 60 days from surgery)

    Measured: "up to 3 months"

  5. Metabolic Response

    Metabolic Response by FDG-Positron emission tomography-computed tomography (PET-CT) scan prior to surgery compared to the baseline test.

    Measured: "presurgery"

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Oct 2019
  2. Study start12 Jun 2018
  3. Primary completion17 Jun 2019
  4. Study completion2 Sep 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
22 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04123925
Sponsor's protocol ID
NICOLE
Acronym
NICOLE
Status last verified
Sep 2019
First submitted
4 Sep 2019
Last updated
12 Jun 2020
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Nivolumab in people with Colon Cancer Stage II/III, run by National Cancer Institute, Naples at 1 site in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Tolerability and Safety (time frame: "up to 5 weeks"). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04123925.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jun 2020.

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