Last updated on February 2019

Combination Chemotherapy With or Without Atezolizumab in Treating Patients With Stage III Colon Cancer and Deficient DNA Mismatch Repair


Brief description of study

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 colon cancer.

Detailed Study Description

PRIMARY OBJECTIVES:

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).

SECONDARY OBJECTIVES:

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 (PRO)-CTCAE.

TERTIARY OBJECTIVES:

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 QOL.

II. To determine if the "immunoscore" can predict the efficacy of atezolizumab for disease-free survival among patients with stage III colon cancer.

III. To assess whether circulating immune cell populations can predict the efficacy of atezolizumab as adjuvant therapy for stage III colon cancer.

IV. To explore the associations of genomic alterations identified in cell-free (cf)DNA with DFS in patients treated with FOLFOX with or without atezolizumab.

V. To assess whether soluble markers of systemic inflammation in blood can predict the efficacy of atezolizumab as adjuvant therapy for stage III colon cancer.

VI. 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.

VII. 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.

VIII. To determine if hypermutation or hyper-indel status is associated with response to atezolizumab.

IX. 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.

X. 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.

XI. To identify overall mutational burden and number of putative tumor neoantigens in colon carcinoma specimens.

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 courses in the absence of disease progression or unacceptable toxicity. Patients also receive atezolizumab IV over 30-60 minutes starting on day 1 of course 1 or 2. Treatment repeats every 14 days for up to 25 courses 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 courses 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.

Clinical Study Identifier: NCT02912559

Contact Investigators or Research Sites near you

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Michigan Cancer Specialists
Roseville, MI United States
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Advanced Breast Care Center PLLC
Warren, MI United States
2.44miles
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Tareq Al Baghdadi

Bhadresh Nayak MD PC-Warren
Warren, MI United States
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Great Lakes Cancer Management Specialists-Macomb Professional Building
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Macomb Hematology Oncology PC
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Michigan Breast Specialists-Warren
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Saint John Macomb-Oakland Hospital
Warren, MI United States
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Bhadresh Nayak MD PC-Sterling Heights
Sterling Heights, MI United States
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Premier Hematology Oncology Care
Sterling Heights, MI United States
5.05miles
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Great Lakes Cancer Management Specialists-Van Elslander Cancer Center
Grosse Pointe Woods, MI United States
5.61miles
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Lymphoma Clinic of Michigan
Grosse Pointe Woods, MI United States
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Michigan Breast Specialists-Grosse Pointe Woods
Grosse Pointe Woods, MI United States
5.61miles
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Tareq Al Baghdadi

Ascension Saint John Hospital
Detroit, MI United States
5.61miles
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Anteneh A. Tesfaye

McLaren Cancer Institute-Macomb
Mount Clemens, MI United States
7.13miles
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William Beaumont Hospital-Grosse Point
Grosse Pointe, MI United States
8.23miles
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Mitchell Folbe MD PC
Sterling Heights, MI United States
8.97miles
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Tareq Al Baghdadi

Great Lakes Cancer Management Specialists-Macomb Medical Campus
Macomb, MI United States
9.94miles
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Michigan Breast Specialists-Macomb Township
Macomb, MI United States
9.94miles
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Recruitment Status: Open


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