eoadjuvant immune checkpoint inhibition and novel IO combinations in early-stage colon cancer. The NICHE trial.

Phase 2

Recruiting

• Conditions: colon carcinoma; 10017991

• Registration Number: NL-OMON53138
• Lead Sponsor: ederlands Kanker Instituut

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 23 April 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: Not specified
• Target Recruitment: 268

Inclusion Criteria

• Signed written informed consent;
• Patients at least 18 years of age;
• Non-metastatic adenocarcinoma of the colon (and rectosigmoid considered as
non-rectal and not undergoing neoadjuvant treatment)
o No signs of distant metastases on CT-scan and physical examination;
o dMMR cohorts 3+6: >cT3 and/or N+
• No clinical obstruction;
• No clinical symptoms or radiological suspicion of perforation;
• Colonoscopy must be performed after informed consent to obtain study-specific
biopsies. If biopsies are not possible, patients cannot be included in the
study;
• WHO performance status of 0 or 1;
• Screening laboratory tests must meet the following criteria and should be
obtained within 7 days prior to randomization/registration: WBC > 2.0 x 10^9/L,
ANC > 1.5x10^9/L, platelets > 100 x 10^9/L, Hemoglobin > 5.0mmol/L. Transfusion
is allowed to obtain an adequate hemoglobin level. Liver function tests: total
bilirubin
< 1.5 upper limit of normal (ULN) (except for subjects with Gilbert syndrome,
who can have total bilirubin <3.0 mg/dL); alkaline phosphatase <2.5 ULN;
transaminases (ASAT/ALAT) <3 x ULN; LDH < 2 x ULN;
• Creatinine clearance (Cockcroft-Gault) of >40 ml/min;
• Women of childbearing potential (WOCBP)* must use appropriate method(s) of
contraception. WOCBP should use an adequate method to avoid pregnancy for 23
weeks (30 days plus the time required for nivolumab to undergo five half-lives)
after the last dose of investigational drug;
• Women of childbearing potential must have a negative serum or urine pregnancy
test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours
prior to the start of nivolumab;
• Men who are sexually active with WOCBP must use any contraceptive method with
a failure rate of less than 1% per year. Men receiving nivolumab and who are
sexually active with WOCBP will be instructed to adhere to contraception for a
period of 31 weeks after the last dose of investigational product. Women who
are not of childbearing potential (i.e., who are postmenopausal or surgically
sterile as well as azoospermic men do not require contraception;
• CT-scan must be performed within 28 days prior to registration;
• No previous treatment with immune checkpoint inhibitors targeting including
but not limited to CTLA-4, PD-1 or PD-L1;
• No previous treatment with chemotherapy for colon cancer.
o For dMMR cohort no previous chemotherapy for any malignancies
• No radiotherapy prior to or planned post-surgery radiotherapy for disease
under study;
• No active malignancies other than disease under study within 3 years prior to
inclusion, except for malignancies with a negligible recurrence rate (e.g. <10%
in 5 years);
• Allergies and Adverse Drug Reaction
o No history of allergy to study drug components
o No history of severe hypersensitivity reaction to any monoclonal antibody
• No intercurrent illnesses, including but not limited to infections, unstable
angina pectoris;
• No underlying medical conditions that, in the Investigator*s opinion, will
make the administration of the study drug hazardous or obscure the
interpretation of toxicity determination of adverse events;
• No positive test for hepatitis B virus surface antigen (HBsAg) or hepatitis C
virus ribonucleic acid (HCV antibody) indicating acute or chronic infect

Exclusion Criteria

• (No) previous treatment with immune checkpoint inhibitors targeting CTLA-4,
PD-1 or PD-L1;
• No radiotherapy prior to or planned post-surgery radiotherapy within this
trial;
• Allergies and Adverse Drug Reaction
O No history of allergy to study drug components
O No history of severe hypersensitivity reaction to any monoclonal antibody
O No history of allergy or severe hypersensitivity to NSAIDs or COX2-I (MSS
tumors)
• No intercurrent illnesses, including but not limited to infections, unstable
angina pectoris
• No positive test for hepatitis B virus surface antigen (HBsAg) or hepatitis C
virus ribonucleic acid (HCV antibody) indicating acute or chronic infection;
• No live vaccines in the 4 weeks prior to inclusion;
• For patients with MSS tumors: no current use of NSAIDs or COX2-inhibitors at
registration and no active peptic ulcer, gastrointestinal bleeding, unstable
ischemic heart disease of thrombus etiology or significant established ischemic
heart disease, peripheral arterial disease and/or cerebrovascular disease;
• No underlying medical conditions that, in the Investigator*s opinion, will
make the administration of the study drug hazardous or obscure the
interpretation of toxicity determination of adverse events;
• No active autoimmune disease or a documented history of autoimmune disease,
or other medical conditions requiring systemic steroid or immunosuppressive
medications, except for subjects with vitiligo, diabetes mellitus type 1,
residual hypothyroidism due to autoimmune condition only requiring hormone
replacement, psoriasis or resolved childhood asthma/atopy not requiring
systemic treatment;
• No conditions requiring systemic treatment with either corticosteroids (> 10
mg daily prednisone equivalents) or other immunosuppressive medications within
14 days of study drug administration. Inhaled or topical steroids and adrenal
replacement doses > 10 mg daily prednisone equivalents are permitted in the
absence of active autoimmune disease;
• No history of uncontrolled medical or psychiatric illness;
• No psychological, familial, sociological or geographical condition
potentially hampering compliance with the study protocol and follow-up
schedule;
No current pregnancy or breastfeeding;
• No active malignancies other than disease under study within 3 years prior to
inclusion, except for malignancies with a negligible recurrence rate (e.g. <10%
in 5 years).

Study & Design

• Study Type: Interventional
• Study Design: Not specified