| Eligibility |
Inclusion Criteria:
The ECOG performance status must be 0 or 1.
Patients must have histologically/pathologically confirmed stage II/III adenocarcinoma of
the colon (per AJCC 8th edition) with R0 resection by open laparotomy or
laparoscopic-assisted colectomy.
There must be documentation by CT scan with contrast that the patient has no evidence of
measurable metastatic disease including assessment of chest, abdomen, and pelvis. (Note:
MRI will be accepted for patients unable to have CT scans with contrast.)
Patients must have completed at least 3 months of a standard adjuvant chemotherapy regimen.
The distal extent of the tumor must be greater than or equal to 12 cm from the anal verge
on colonoscopy or above the peritoneal reflection as documented during surgery or on
pathology specimen.
Patients with microsatellite stable (MSS) proficient mismatch repair (pMMR) tumors are
eligible.
Patients must be ctDNA-positive as determined by the Natera Signatera™ assay from samples
submitted to Natera within less than or equal to 6 weeks after completing adjuvant
chemotherapy. The study will provide pre-entry ctDNA testing for consenting stage III
patients. Note: Stage II colon cancer patients may be ctDNA tested via the FC-12 study
provided all the following criteria are met:
- The patient must have been previously determined to be ctDNA-positive by Natera's
Signatera™ commercial assay outside of the study (i.e., at the time of resection).
- The patient has received at least 3 months of a standard chemotherapy regimen.
- Patients must sign the FC-12 ctDNA Screening consent and samples must be submitted to
Natera within less than or equal to 6 weeks after completion of the adjuvant
chemotherapy for reconfirmation of ctDNA-positivity by the Signatera™ assay via the
FC-12 study.
Patients must be able to begin study therapy within 14 weeks after the completion of
adjuvant chemotherapy.
At the time of study entry, blood counts performed within 2 weeks prior to study entry must
meet the following criteria:
- ANC must be greater than or equal to 1500/mm3,
- Platelet count must be greater than or equal to 100,000/mm3; and
- Hemoglobin must be greater than or equal to 9 g/dL. (Note: transfusions maybe used to
correct hemoglobin for patients experiencing anemia from therapy who otherwise would
be eligible for the study.)
- Albumin greater than 3.0 g/dL
The following criteria for evidence of adequate hepatic function performed within 2 weeks
prior to study entry must be met:
- Total bilirubin must be less than or equal to 1.5 x ULN. (Note: any elevated bilirubin
has to be asymptomatic.)
- AST and ALT must be less than or equal to 3.0 x ULN for the lab. (Note: In patients
with elevated ALT or AST, the values must be stable for at least 2 weeks and with no
evidence of biliary obstruction on imaging.)
Creatinine must be less than or equal to 3.0 x upper limit of normal (ULN).
All chemotherapy toxicities (excluding alopecia and amenorrhea) must be less than grade 2
at the time study therapy is to begin.
Patients must have no evidence of opportunistic infections.
Female patients of childbearing potential must have a negative serum pregnancy within 72
hours prior to receiving the first dose of study medication. If the urine test is positive
or cannot be confirmed as negative, a serum pregnancy test will be required.
Male and female patients with reproductive potential must agree to use accepted effective
methods of contraception while receiving study therapy and for at least 90 days (3 months)
after the completion of study therapy. Note: Abstinence is acceptable if this is the usual
lifestyle and preferred contraception for the patient.
Exclusion Criteria:
Diagnosis of anal or small bowel carcinoma.
Colon cancer other than adenocarcinoma, e.g., sarcoma, lymphoma, carcinoid.
Patients with MSI-high defective mismatch repair (dMMR) tumors are ineligible.
An elevated CEA above institutional normal value. For smokers a higher institution ULN is
acceptable.
Use and/or receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy,
targeted therapy, biologic therapy, monoclonal anti-bodies) or radiation therapy within 4
weeks prior to receiving first dose of study therapy.
Persistent diarrhea greater than grade 1.
History of active or latent tuberculosis (TB) infection. If presence of TB (active or
latent) is established, then treatment for TB must be completed according to local
guidelines prior to the screening.
Active untreated or uncontrolled systemic fungal, bacterial or viral infections, or active
infection requiring systemic anti-infectious therapy.
Current or history of systemic autoimmune disease requiring systemic immunosuppressive
therapy will not be allowed. Note: the following will not be exclusionary: 1) the presence
of laboratory evidence of autoimmune disease (e.g. positive antinuclear antibody titer or
lupus anticoagulant) without associated symptoms; 2) clinical evidence of vitiligo or other
forms of depigmenting illness; 3) mild autoimmunity not impacting the function of major
organs (e.g. controlled Hashimoto thyroiditis, limited psoriasis).
Patients will be excluded if they are on systemic steroid therapy that cannot be
discontinued (except for the use of prednisone or equivalent less than 0.125mg/kg/day as
replacement therapy). Inhaled or topical steroids are permitted.
Receipt of live attenuated vaccination within 30 days prior to study entry.
Active or chronic hepatitis B virus (HBV) or hepatitis C virus (HCB) infections.
Note: Patients with a history of hepatitis C virus (HCV) infection must have been treated
and with confirmation of cure, can be eligible.
Active infection or chronic infection requiring chronic suppressive antibiotics.
History of allogeneic organ or bone marrow transplantation.
Any of the following cardiac conditions:
- documented NYHA Class III or IV congestive heart failure,
- symptomatic arrhythmia.
- History of myocardial infarction (MI), angina pectoris, or coronary artery bypass
graft (CABG) within 6 months prior to starting study treatment
- Clinically significant cardiac arrhythmias
- Uncontrolled congestive heart failure Active documented inflammatory bowel disease
(e.g., Crohn's disease, ulcerative colitis).
Major surgical procedure within 28 days prior to study entry.
Other malignancies: unless the patient is considered disease-free and has completed therapy
for the malignancy greater than or equal to 12 months prior to study entry. Patients with
the following cancers are eligible if diagnosed and treated within the past 12 months:
carcinoma in situ of the cervix, and basal cell and squamous cell carcinoma of the skin.
Other in situ neoplasms will be reviewed by the Protocol Officer and/or Protocol Chair.
Psychiatric or addictive disorders or other conditions that in the opinion of the
investigator would preclude the patient from meeting the study requirements or interfere
with interpretation of study results.
Pregnancy or lactation at the time of study entry.
Use of any investigational agent within 4 weeks prior to the first dose of study therapy.
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