This study will look at the recurrence-free survival of microsatellite-stable (MSS) colon cancer in patients are ctDNA (circulating tumor DNA) positive and treated with gevokizumab.
NSABP FC-12 is a single-arm, multi-centered phase II study to evaluate recurrence-free survival in patients with stage II/III microsatellite-stable (MSS) colon cancer who have undergone curative surgery, adjuvant chemotherapy, are ctDNA (circulating tumor DNA)-positive and treated with gevokizumab. Patients with stage III resected MSS colon cancer (CRC) who are less than or equal to (≤) 6 weeks after completion of at least 3 months of a standard adjuvant chemotherapy regimen, who are interested in participating in the FC-12 study are eligible for pre-entry ctDNA testing for ctDNA-positivity using the Signatera™ assay via the FC-12 study. Within 6 weeks after completion of adjuvant therapy, stage III patients who have signed the FC-12 Pre-Screening ctDNA consent will have blood and primary tissue samples collected and submitted to Natera for ctDNA evaluation. Commercial ctDNA assay results will not be accepted for study entry. For 150 patients screened in this CRC population, the ctDNA-positivity rate is expected to be approximately 20%. Note: Patients with stage II MSS colon cancer who were determined to be ctDNA-positive by Natera's Signatera™ commercial assay (i.e., outside of the study) after curative resection may be considered for ctDNA confirmation of ctDNA-positivity via the FC-12 study provided that all the following are met: * The patient has completed of at least 3 months of a standard adjuvant chemotherapy regimen. * ctDNA samples will be collected and submitted for ctDNA-positivity confirmation by the Signatera™ assay via the FC-12 study within ≤ 8 weeks after the patient has completed adjuvant chemotherapy. * The patient otherwise meets eligibility criteria. And, * the patient will be able to start study therapy within 14 weeks after completion of adjuvant chemotherapy. All eligible consenting patients who have ctDNA-positivity confirmed via the FC-12 study must begin study therapy within 14 weeks from the completion of adjuvant chemotherapy. Patients will receive gevokizumab (120mg IV) on Day 1 of every 28-day cycle for a maximum of 1 year (e.g., 13 cycles: 1 cycle = 28 days). Patients will continue to receive 13 cycles (1 year) of study therapy unless the patient elects to discontinue study medication, does not adhere to the study per the investigator, experiences intolerable drug toxicity, or has disease recurrence confirmed by imaging. ctDNA will be monitored at Weeks 8, 12, 24, 36, 48, 60, and 72 unless disease recurrence is documented by imaging. Imaging will include CT scan of chest, abdomen and pelvis and will occur every 24 weeks (6 months) for the duration of the patient's participation in the study or until imaging confirms recurrence. All patients will be followed for approximately 18 months after initiating study therapy or until imaging confirms recurrence whichever comes first. The sample size and maximum enrollment for this single arm phase II trial is approximately 31 patients with stage II patient accrual capped at no more than 8 patients. Enrolled patients who withdraw consent prior to receiving study therapy or who are unable to begin study therapy will be replaced. Safety assessments will occur at intervals per protocol (Section 5.0). Drug toxicity will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 5.0 (CTCAE 5.0). Submission of archived tumor tissue and blood for FC-12 correlative science studies will be a requirement for all patients enrolled into the study. Serial blood samples will be collected at specified time points throughout the study for gevokizumab pharmacokinetics (PKs) and anti-drug antibody (ADA) assessment. Stool samples for FC-12 correlative science microbiome studies are optional.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
120mg IV on day 1 of every 28-day cycle for 1 year (maximum of 13 cycles)
ctDNA monitoring at weeks 8, 12, 24, 36, 48, 60 and 72 unless disease recurrence is documented.
UF Health Davis Cancer Pavilion and Shands Med Plaza
Gainesville, Florida, United States
University of Iowa
Iowa City, Iowa, United States
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, United States
Wake Forest Baptist Health
Winston-Salem, North Carolina, United States
Recurrence-free survival (RFS) at one year
Percentage of patients alive absent recurrence
Time frame: From the initiation of study therapy through 1 year of follow-up
Clearance of ctDNA
Percentage of patients who have converted to negative ctDNA assay at 8 weeks from start of study therapy
Time frame: From the initiation of study therapy to 8 weeks
Duration of Recurrence-free survival (RFS) with ctDNA clearance at 8 weeks from start of study therapy
Percentage of patients who have converted to a negative ctDNA assay at 8 weeks and are absent recurrence at one year
Time frame: From the initiation of study therapy through 1 year of follow-up
Duration of Recurrence-free survival (RFS) without ctDNA clearance at 8 weeks
Percentage of patients who have not converted to a negative ctDNA assay at 8 weeks and are absent a recurrence at one year.
Time frame: From the initiation of study therapy through 1 year of follow-up
Frequency of adverse events assessed using CTCAE 5.0
Distribution of patients (percentage) by maximum observed grade of adverse event (0-5).
Time frame: From beginning of study therapy until 90 days after last dose, approximately 15 months
Serum concentration
Describe serum concentration (pharmacokinetics) of gevokizumab
Time frame: From beginning of study therapy until 30 days after last dose
Immunogenicity
Describe anti-drug antibodies to gevokizumab
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AHN Cancer Institute
Pittsburgh, Pennsylvania, United States
Time frame: From beginning of study therapy until 30 days after last dose