This phase III trial studies combination chemotherapy and atezolizumab to see how well it
works compared with combination chemotherapy alone in treating patients with stage III colon
cancer and deficient deoxyribonucleic acid (DNA) mismatch repair. Drugs used in combination
chemotherapy, such as oxaliplatin, leucovorin calcium, and fluorouracil, work in different
ways to stop the growth of tumor cells, either by killing the cells, by stopping them from
dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such
as atezolizumab, may help the body's immune system attack the cancer, and may interfere with
the ability of tumor cells to grow and spread. Giving combination chemotherapy with
atezolizumab may work better than combination chemotherapy alone in treating patients with
I. To determine whether atezolizumab combined with oxaliplatin, leucovorin calcium, and
fluorouracil (FOLFOX) and its continuation as monotherapy can significantly improve
disease-free survival (DFS) compared to FOLFOX alone in patients with stage III colon cancers
and deficient DNA mismatch repair (dMMR).
I. To determine whether atezolizumab combined with FOLFOX and its continuation as monotherapy
can significantly improve overall survival compared to FOLFOX alone in patients with stage
III colon cancers and dMMR.
II. To assess the adverse events (AE) profile and safety of each treatment arm, using the
Common Terminology Criteria for Adverse Events (CTCAE) and patient related outcomes
QUALITY OF LIFE OBJECTIVE:
I. To determine the impact of the addition of atezolizumab to FOLFOX on patient-reported
neuropathy, health-related quality of life (QOL), and functional domains of health-related
POTENTIAL CORRELATIVE SCIENCE OBJECTIVES:
I. To determine if the "immunoscore" can predict the efficacy of atezolizumab for
disease-free survival among patients with stage III colon cancer.
II. To assess whether circulating immune cell populations can predict the efficacy of
atezolizumab as adjuvant therapy for stage III colon cancer.
III. To explore the associations of genomic alterations identified in cell-free (cf)DNA with
DFS in patients treated with FOLFOX with or without atezolizumab.
IV. To assess whether soluble markers of systemic inflammation in blood can predict the
efficacy of atezolizumab as adjuvant therapy for stage III colon cancer.
V. To assess the relationship between baseline plasma 25(OH) D levels, change in 25(OH)D
levels, and DFS and overall survival (OS) in patients with stage III colon cancer receiving
FOLFOX +/- atezolizumab.
VI. To determine the ability of using fecal microbiota and their metabolic products to
predict survival benefit from anti-PD-L1 antibody therapy in dMMR colon cancer patients.
VII. To determine if hypermutation or hyper-indel status is associated with response to
VIII. To determine if unique messenger ribonucleic acid (mRNA) expression signatures are
predictive of disease-free survival among patients receiving adjuvant chemotherapy for stage
III colon cancer.
IX. To determine if the efficacy of atezolizumab differs among dMMR cancers due to germline
MMR mutation (MLH1, MSH2, MSH6, PMS2) versus those with MLH1 hypermethylation and CIMP in
patients with stage III colon cancer.
X. To identify overall mutational burden and number of putative tumor neoantigens in colon
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive oxaliplatin intravenously (IV) over 2 hours and leucovorin calcium IV
over 2 hours on day 1, and fluorouracil IV as a bolus on day 1, then continuously over 46
hours on days 1-3. Treatment repeats every 14 days for up to 12 cycles in the absence of
disease progression or unacceptable toxicity. Patients also receive atezolizumab IV over
30-60 minutes starting on day 1 of cycle 1 or 2. Treatment repeats every 14 days for up to 25
cycles in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours
on day 1, and fluorouracil IV as a bolus on day 1, then continuously over 46 hours on days
1-3. Treatment repeats every 14 days for up to 12 cycles in the absence of disease
progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for recurrence every 6 months
for 2 years, then annually for 3 years. Patients are also followed up for survival every 6
months for up to 8 years.
Hereditary Neoplastic Syndrome,
Deficiency of DNA repair, NOS,
Colon Cancer Screening,
Colon cancer; rectal cancer,
Stage III Colon Cancer AJCC v7,
Stage IIIA Colon Cancer AJCC v7,
Stage IIIB Colon Cancer AJCC v7,
Stage IIIC Colon Cancer AJCC v7,
Adenocarcinoma of the Colon,
Hereditary Cancer Syndromes,
adenocarcinoma of colon,
If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.
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