Last updated on November 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.

QUALITY OF LIFE 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.

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 atezolizumab.

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 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 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.

Clinical Study Identifier: NCT02912559

Find a site near you

Start Over

Mills-Peninsula Medical Center

Burlingame, CA United States
  Connect »

Adena Regional Medical Center

Chillicothe, OH United States
  Connect »

Rochester General Hospital

Rochester, NY United States
  Connect »

Decatur Memorial Hospital

Decatur, IL United States
  Connect »

Mary Imogene Bassett Hospital

Cooperstown, NY United States
  Connect »

Freeman Health System

Joplin, MO United States
  Connect »

Reid Health

Richmond, IN United States
  Connect »

Florida Hospital Orlando

Orlando, FL United States
  Connect »

Middlesex Hospital

Middletown, CT United States
  Connect »

Boulder Community Hospital

Boulder, CO United States
  Connect »

Rapid City Regional Hospital

Rapid City, SD United States
  Connect »

Ochsner Medical Center Jefferson

New Orleans, LA United States
  Connect »

Olathe Medical Center

Olathe, KS United States
  Connect »

Mercy Hospital Joplin

Joplin, MO United States
  Connect »

Grand Valley Oncology

Grand Junction, CO United States
  Connect »

Kootenai Cancer Center

Post Falls, ID United States
  Connect »

Saint Joseph Mercy Hospital

Ann Arbor, MI United States
  Connect »

Sovah Health Martinsville

Martinsville, VA United States
  Connect »

Farmington Health Center

Farmington, UT United States
  Connect »

Bryn Mawr Hospital

Bryn Mawr, PA United States
  Connect »

Illinois CancerCare-Bloomington

Bloomington, IL United States
  Connect »

Saint Cloud Hospital

Saint Cloud, MN United States
  Connect »

Virginia Cancer Institute

Richmond, VA United States
  Connect »

Meharry Medical College

Nashville, TN United States
  Connect »

University of Virginia Cancer Center

Charlottesville, VA United States
  Connect »

Shenandoah Oncology PC

Winchester, VA United States
  Connect »

Vidant Oncology-Kinston

Kinston, NC United States
  Connect »

Sharp Memorial Hospital

San Diego, CA United States
  Connect »

Katmai Oncology Group

Anchorage, AK United States
  Connect »

Saint Francis Medical Center

Cape Girardeau, MO United States
  Connect »

Bay Area Hospital

Coos Bay, OR United States
  Connect »

Saint Francis Cancer Center

Greenville, SC United States
  Connect »

PCR Oncology

Arroyo Grande, CA United States
  Connect »

Island Urology

Honolulu, HI United States
  Connect »

Heartland Regional Medical Center

Saint Joseph, MO United States
  Connect »

Kaiser Permanente-Lone Tree

Lone Tree, CO United States
  Connect »

Randolph Hospital

Asheboro, NC United States
  Connect »

Dickstein Cancer Treatment Center

White Plains, NY United States
  Connect »

Lowell General Hospital

Lowell, MA United States
  Connect »

Mercy Hospital

Coon Rapids, MN United States
  Connect »

SIH Cancer Institute

Carterville, IL United States
  Connect »

Self Regional Healthcare

Greenwood, SC United States
  Connect »

Good Samaritan Hospital

Corvallis, OR United States
  Connect »

Margaret R Pardee Memorial Hospital

Hendersonville, NC United States
  Connect »

Kaiser Permanente-Anaheim

Anaheim, CA United States
  Connect »

Kaiser Permanente-Baldwin Park

Baldwin Park, CA United States
  Connect »

Kaiser Permanente-Bellflower

Bellflower, CA United States
  Connect »

Kaiser Permanente-Fontana

Fontana, CA United States
  Connect »

Kaiser Permanente - Harbor City

Harbor City, CA United States
  Connect »

Kaiser Permanente-Irvine

Irvine, CA United States
  Connect »

Kaiser Permanente-Cadillac

Los Angeles, CA United States
  Connect »

Memorial Medical Center

Modesto, CA United States
  Connect »

Kaiser Permanente-Ontario

Ontario, CA United States
  Connect »

Kaiser Permanente - Panorama City

Panorama City, CA United States
  Connect »

Kaiser Permanente-Riverside

Riverside, CA United States
  Connect »

Kaiser Permanente-San Marcos

San Marcos, CA United States
  Connect »

City of Hope West Covina

West Covina, CA United States
  Connect »

Kaiser Permanente-Woodland Hills

Woodland Hills, CA United States
  Connect »

Penrose-Saint Francis Healthcare

Colorado Springs, CO United States
  Connect »

Swedish Medical Center

Englewood, CO United States
  Connect »

Kaiser Permanente-Rock Creek

Lafayette, CO United States
  Connect »

Longmont United Hospital

Longmont, CO United States
  Connect »

McKee Medical Center

Loveland, CO United States
  Connect »

Queen's Medical Center

Honolulu, HI United States
  Connect »

Kootenai Medical Center

Coeur d'Alene, ID United States
  Connect »

Kootenai Cancer Clinic

Sandpoint, ID United States
  Connect »

Illinois CancerCare-Carthage

Carthage, IL United States
  Connect »

Centralia Oncology Clinic

Centralia, IL United States
  Connect »

Northwestern University

Chicago, IL United States
  Connect »

Carle on Vermilion

Danville, IL United States
  Connect »

Crossroads Cancer Center

Effingham, IL United States
  Connect »

Illinois CancerCare-Galesburg

Galesburg, IL United States
  Connect »

Illinois CancerCare-Princeton

Princeton, IL United States
  Connect »

Carle Cancer Center

Urbana, IL United States
  Connect »

Sidney and Lois Eskenazi Hospital

Indianapolis, IN United States
  Connect »

Iowa Cancer Specialists

Davenport, IA United States
  Connect »

Mercy Medical Center-West Lakes

West Des Moines, IA United States
  Connect »

Lawrence Memorial Hospital

Lawrence, KS United States
  Connect »

Saint Joseph Hospital East

Lexington, KY United States
  Connect »

Mary Bird Perkins Cancer Center

Baton Rouge, LA United States
  Connect »

Penobscot Bay Medical Center

Rockport, ME United States
  Connect »

Bronson Battle Creek

Battle Creek, MI United States
  Connect »

Saint Joseph Mercy Brighton

Brighton, MI United States
  Connect »

Saint Joseph Mercy Canton

Canton, MI United States
  Connect »

Saint Joseph Mercy Chelsea

Chelsea, MI United States
  Connect »

Henry Ford Hospital

Detroit, MI United States
  Connect »

Weisberg Cancer Treatment Center

Farmington Hills, MI United States
  Connect »

Hurley Medical Center

Flint, MI United States
  Connect »

Academic Hematology Oncology Specialists

Grosse Pointe Woods, MI United States
  Connect »

West Michigan Cancer Center

Kalamazoo, MI United States
  Connect »

McLaren-Greater Lansing

Lansing, MI United States
  Connect »

Sparrow Hospital

Lansing, MI United States
  Connect »

Hope Cancer Clinic

Livonia, MI United States
  Connect »

Saint Mary Mercy Hospital

Livonia, MI United States
  Connect »

McLaren Cancer Institute-Macomb

Mount Clemens, MI United States
  Connect »

Saint Joseph Mercy Oakland

Pontiac, MI United States
  Connect »

McLaren-Port Huron

Port Huron, MI United States
  Connect »

Marie Yeager Cancer Center

Saint Joseph, MI United States
  Connect »

Ascension Saint Joseph Hospital

Tawas City, MI United States
  Connect »

Munson Medical Center

Traverse City, MI United States
  Connect »

Henry Ford West Bloomfield Hospital

West Bloomfield, MI United States
  Connect »

Metro Health Hospital

Wyoming, MI United States
  Connect »

Fairview Ridges Hospital

Burnsville, MN United States
  Connect »

Unity Hospital

Fridley, MN United States
  Connect »

Abbott-Northwestern Hospital

Minneapolis, MN United States
  Connect »

Park Nicollet Clinic - Saint Louis Park

Saint Louis Park, MN United States
  Connect »

Regions Hospital

Saint Paul, MN United States
  Connect »

Ridgeview Medical Center

Waconia, MN United States
  Connect »

Rice Memorial Hospital

Willmar, MN United States
  Connect »

Capital Region Southwest Campus

Jefferson City, MO United States
  Connect »

Research Medical Center

Kansas City, MO United States
  Connect »

Bozeman Deaconess Hospital

Bozeman, MT United States
  Connect »

Community Medical Hospital

Missoula, MT United States
  Connect »

CHI Health Saint Francis

Grand Island, NE United States
  Connect »

CHI Health Good Samaritan

Kearney, NE United States
  Connect »

OptumCare Cancer Care at Oakey

Las Vegas, NV United States
  Connect »

Valley Hospital

Ridgewood, NJ United States
  Connect »

Cone Health Cancer Center

Greensboro, NC United States
  Connect »

AdventHealth Hendersonville

Hendersonville, NC United States
  Connect »

Vidant Oncology-Kenansville

Kenansville, NC United States
  Connect »

Vidant Oncology-Richlands

Richlands, NC United States
  Connect »

Indu and Raj Soin Medical Center

Beavercreek, OH United States
  Connect »

Aultman Health Foundation

Canton, OH United States
  Connect »

Miami Valley Hospital South

Centerville, OH United States
  Connect »

Grant Medical Center

Columbus, OH United States
  Connect »

Doctors Hospital

Columbus, OH United States
  Connect »

Miami Valley Hospital

Dayton, OH United States
  Connect »

Armes Family Cancer Center

Findlay, OH United States
  Connect »

Blanchard Valley Hospital

Findlay, OH United States
  Connect »

Orion Cancer Care

Findlay, OH United States
  Connect »

Dayton Physicians LLC-Atrium

Franklin, OH United States
  Connect »

Dayton Physicians LLC-Wayne

Greenville, OH United States
  Connect »

Wayne Hospital

Greenville, OH United States
  Connect »

Greater Dayton Cancer Center

Kettering, OH United States
  Connect »

First Dayton Cancer Care

Kettering, OH United States
  Connect »

Kettering Medical Center

Kettering, OH United States
  Connect »

OhioHealth Mansfield Hospital

Mansfield, OH United States
  Connect »

Marietta Memorial Hospital

Marietta, OH United States
  Connect »

Hillcrest Hospital Cancer Center

Mayfield Heights, OH United States
  Connect »

Licking Memorial Hospital

Newark, OH United States
  Connect »

Southern Ohio Medical Center

Portsmouth, OH United States
  Connect »

North Coast Cancer Care

Sandusky, OH United States
  Connect »

South Pointe Hospital

Warrensville Heights, OH United States
  Connect »

Geisinger Medical Center

Danville, PA United States
  Connect »

Jefferson Hospital

Jefferson Hills, PA United States
  Connect »

Lewistown Hospital

Lewistown, PA United States
  Connect »

Riddle Memorial Hospital

Media, PA United States
  Connect »

Paoli Memorial Hospital

Paoli, PA United States
  Connect »

Community Medical Center

Scranton, PA United States
  Connect »

Geisinger Medical Group

State College, PA United States
  Connect »

Lankenau Medical Center

Wynnewood, PA United States
  Connect »

Saint Francis Hospital

Greenville, SC United States
  Connect »

Avera Cancer Institute

Sioux Falls, SD United States
  Connect »

Sandra L Maxwell Cancer Center

Cedar City, UT United States
  Connect »

United Hospital Center

Bridgeport, WV United States
  Connect »

Camden Clark Medical Center

Parkersburg, WV United States
  Connect »

Duluth Clinic Ashland

Ashland, WI United States
  Connect »

Aurora Health Center-Fond du Lac

Fond Du Lac, WI United States
  Connect »

Aurora Cancer Care-Grafton

Grafton, WI United States
  Connect »

Aurora BayCare Medical Center

Green Bay, WI United States
  Connect »

Aurora Cancer Care-Milwaukee

Milwaukee, WI United States
  Connect »

Aurora Sinai Medical Center

Milwaukee, WI United States
  Connect »

ProHealth D N Greenwald Center

Mukwonago, WI United States
  Connect »

Aurora Cancer Care-Racine

Racine, WI United States
  Connect »

Genesis Cancer Care Institute

Davenport, IA United States
  Connect »

Health Partners Inc

Minneapolis, MN United States
  Connect »

M D Anderson Cancer Center

Houston, TX United States
  Connect »

AdventHealth Orlando

Orlando, FL United States
  Connect »

Lakeview Hospital

Stillwater, MN United States
  Connect »

Spartanburg Medical Center

Spartanburg, SC United States
  Connect »

Yale University

New Haven, CT United States
  Connect »

East Carolina University

Greenville, NC United States
  Connect »

Logan Regional Hospital

Logan, UT United States
  Connect »

AMG Libertyville - Oncology

Libertyville, IL United States
  Connect »

United Hospital

Saint Paul, MN United States
  Connect »

Chambersburg Hospital

Chambersburg, PA United States
  Connect »

Beebe Health Campus

Rehoboth Beach, DE United States
  Connect »

Essentia Health Sandstone

Sandstone, MN United States
  Connect »