A Study Evaluating Regorafenib Following Completion of Standard Chemotherapy for Patients With Colon Cancer

NCT02664077 | Terminated Phase 3 DMC

• 2 other identifiers: NSABP C-1317808
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 51

Brief Summary

This study is a randomized, double-blind, post-chemotherapy, adjuvant phase III clinical trial. The primary aim of this study is to determine the value of regorafenib in improving disease-free survival (DFS). Patients with Stage III (IIIB or IIIC) colon cancer as defined by the 7th Edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual are randomized 1:1 to placebo or the experimental agent regorafenib following completion of at least four months of standard adjuvant therapy (e.g., 5-fluorouracil, leucovorin, oxaliplatin (FOLFOX) , capecitabine, oxaliplatin (CapeOx), and other).

Conditions

Stage III (IIIB or IIIC) Colon Cancer

Keywords

NSABP; Colon cancer; Regorafenib; Stage III; Adjuvant therapy

Outcome Measures

Primary Outcomes (1)

• Disease-free survival (DFS) - time from randomization until first colon cancer recurrence, second primary colon cancer, or death due to any cause.

  To determine whether treatment with regorafenib following adjuvant therapy improves disease-free survival (DFS) in patients with Stage IIIB or IIIC colon cancer

  Beginning at day 1 of cycle 3 (each cycle = 28 days) and every 6 months until study closure about 10 years

Secondary Outcomes (7)

• Overall Survival (OS) - time from randomization until death from any cause.

  Day 1 of every cycle of chemotherapy then 30 days post study therapy, then every 6 months (years 3-5) then yearly (years 6 & 7)

• Toxicity - frequency and severity of adverse events categorized using the NCI Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0)

  Every study visit through 30 days following study therapy

• Compliance - Time to discontinuation of study therapy.

  Every study visit through discontinuation of study therapy, assessed for up to 24 months

• Correlative Science - Biomarker evaluations

  Before randomization, prior to beginning Cycle 6, every 6 months through year 5, and at the end of study therapy (maximum of 2 years).

• Correlative Science - Pharmacokinetics - Plasma regorafenib concentrations

  Day 15 of Cycle 1 and Cycle 2 of study therapy.

Study Arms (2)

Group 1: Regorafenib

EXPERIMENTAL

Patients receive regorafenib orally once daily for 21 days of a 28 day cycle for a total of 26 cycles.

Drug: Regorafenib

Group 2: Placebo

PLACEBO COMPARATOR

Patients receive placebo orally once daily for 21 days of a 28 day cycle for a total of 26 cycles.

Drug: Placebo

Interventions

Regorafenib DRUG

3 tablets once a day by mouth for 21 consecutive days of 28 day cycle for 26 cycles

Also known as: Stivarga

Group 1: Regorafenib

Placebo DRUG

3 tablets once a day by mouth for 21 consecutive days of 28 day cycle for 26 cycles

Group 2: Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The Eastern Cooperative Oncology Group (ECOG) performance status must be 0-1
• There must be histologic confirmation of high risk, adenocarcinoma of the colon defined as AJCC 7th Edition Stage IIIB or IIIC.
• The patient must have had an en bloc complete gross resection of tumor (curative resection) by open laparotomy or laparoscopically-assisted colectomy. The distal extent of the tumor must have been greater than or equal to 12 cm from the anal verge. (Patients who have had a two-stage surgical procedure to first provide a decompression colostomy and then in a later procedure to have a surgical resection are eligible.)
• Imaging (positron emission tomography/computed tomography (PET/CT) scan, CT scan, or magnetic resonance imaging (MRI)) of chest, abdomen, and pelvis must be performed within 90 days prior to randomization and must demonstrate no evidence of metastatic disease. If findings noted in imaging study reports are equivocal, the determination of whether or not the findings represent metastatic disease will be at the investigator's discretion.
• The patient must be able to swallow oral medication.
• The patient must have completed at least 4 months of adjuvant chemotherapy (i.e., FOLFOX, CapeOx, or other, such as 5-fluorouracil, leucovorin, oxaliplatin (FLOX), 5-fluorouracil/leucovorin (5FU/LV), capecitabine).
• The interval between completion of standard adjuvant chemotherapy and randomization must be less than or equal to 60 days.
• Blood counts performed within 28 days prior to randomization must meet the following criteria:
• Absolute neutrophil count (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.
• The following criteria for evidence of adequate hepatic function performed within 4 weeks prior to randomization must be met:
• total bilirubin must be less than or equal to 1.5 x upper limit of normal (ULN); and
• alkaline phosphatase must be less than or equal to 2 x ULN; and
• Asparate aminotransferase (AST) and alanine aminotransferase (ALT) must be less than or equal to 2 x ULN for the lab. (Note: If AST and/or ALT greater than ULN, serologic testing for Hepatitis B and C must be performed and results must be negative.)

You may not qualify if:

• Isolated, distant, or non-contiguous intra-abdominal metastases, even if resected.
• Colon cancer other than adenocarcinoma (e.g., sarcoma, lymphoma, carcinoid).
• Prior history of invasive adenocarcinoma of colon or rectum.
• Patients with active autoimmune disease. (Patients with endocrine autoimmune diseases requiring replacement therapy alone are allowed.)
• Gastroduodenal ulcer(s) determined by endoscopy to be active.
• Any malabsorption condition.
• Known history of human immunodeficiency virus (HIV) infection or chronic or active hepatitis B or hepatitis C requiring treatment with antiviral therapy.
• Any concomitant systemic therapy or radiation therapy initiated for this malignancy.
• Active infection, or chronic infection requiring chronic suppressive antibiotics.
• Persistent CTCAE v4.0 greater than or equal to grade 2 diarrhea regardless of etiology.
• Know history of allografts (including corneal transplant).
• Chronic daily treatment with corticosteroids with a dose of greater than or equal to 10 mg/day methylprednisolone equivalent (excluding inhaled steroids), or any other immunosuppressive drugs.
• Any significant bleeding (greater than or equal to grade 3, hemorrhage) that is not related to the primary colon tumor within 6 months before randomization.
• Any of the following cardiac conditions:
• documented New York Heart Association (NYHA) Class III or IV congestive heart failure;

Sponsors & Collaborators

• NSABP Foundation Inc: lead
• Bayer: collaborator

Study Sites (51)

St. Joseph Hospital of Orange

Orange, California, 92868, United States

Location

St. Joseph Heritage Healthcare

Santa Rosa, California, 95403, United States

Location

Kaiser Permanente Medical Center - Vallejo

Vallejo, California, 94589, United States

Location

Colorado Cancer Research Program

Denver, Colorado, 80222, United States

Location

Yale University

New Haven, Connecticut, 06510, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

Mount Sinai Comprehensive Cancer Center

Miami Beach, Florida, 33140, United States

Location

Memorial Health University Medical Center

Savannah, Georgia, 31404, United States

Location

Cancer Care Specialists of Illinois - Decatur Memorial Hospital

Decatur, Illinois, 62526, United States

Location

Edward Hospital Cancer Center

Naperville, Illinois, 60540-7499, United States

Location

Carle Cancer Center

Urbana, Illinois, 61801, United States

Location

Northern Indiana Cancer Research Consortium

South Bend, Indiana, 46628, United States

Location

Oncology Associates at Mercy Medical Center

Cedar Rapids, Iowa, 52403, United States

Location

Genesis Medical Center - West Campus

Davenport, Iowa, 52804, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

Covenant Cancer Treatment Center

Waterloo, Iowa, 50702, United States

Location

Norton Cancer Institute, Norton Healthcare Pavilion

Louisville, Kentucky, 40202, United States

Location

Tulane University Health Sciences Center

New Orleans, Louisiana, 70112, United States

Location

New England Cancer Specialists

Scarborough, Maine, 04074, United States

Location

Berkshire Medical Center Cancer and Infusion Center

Pittsfield, Massachusetts, 01201, United States

Location

Breslin Cancer Center

Lansing, Michigan, 48910, United States

Location

Metro Minnesota Community Oncology Research Consortium

Saint Louis Park, Minnesota, 55416, United States

Location

Missouri Valley Cancer Consortium

Omaha, Nebraska, 68106, United States

Location

Nevada Cancer Research Foundation, Inc.

Las Vegas, Nevada, 89106, United States

Location

MD Anderson Cancer Center at Cooper

Camden, New Jersey, 08103, United States

Location

Monmouth Medical Center

Long Branch, New Jersey, 07740-6395, United States

Location

Newark Beth Israel Medical Center

Newark, New Jersey, 07112, United States

Location

Community Medical Center

Toms River, New Jersey, 08755, United States

Location

Waverly Hematology Oncology

Cary, North Carolina, 27511, United States

Location

CaroMont Regional Medical Center

Gastonia, North Carolina, 28054, United States

Location

Margaret R. Pardee Memorial Hospital

Hendersonville, North Carolina, 28791, United States

Location

First Health of the Carolinas Cancer Center

Pinehurst, North Carolina, 28374, United States

Location

Wake Forest Baptist Health

Winston-Salem, North Carolina, 27157, United States

Location

James Cancer Hospital and Solove Research Institute at the Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Toledo Clinic Cancer Center

Toledo, Ohio, 43623, United States

Location

Abington Hospital -Jefferson South

Abington, Pennsylvania, 19001, United States

Location

Penn State Cancer Institute at Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033-0850, United States

Location

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

Allegheny General Hospital

Pittsburgh, Pennsylvania, 15212, United States

Location

UPMC Cancer Centers

Pittsburgh, Pennsylvania, 15232, United States

Location

Guthrie Medical Group, PC

Sayre, Pennsylvania, 18840, United States

Location

Scranton Hematology Oncology

Scranton, Pennsylvania, 18510, United States

Location

Reading Hospital - McGlinn Cancer Institute

West Reading, Pennsylvania, 19611, United States

Location

AnMed Health Cancer Center

Anderson, South Carolina, 29621, United States

Location

McLeod Cancer Center for Treatment and Research

Florence, South Carolina, 29502, United States

Location

Wellmont Medical Associates Oncology and Hematology

Kingsport, Tennessee, 37660, United States

Location

Thompson Cancer Survival Center

Knoxville, Tennessee, 37916, United States

Location

Joe Arrington Cancer Research and Treatment Center

Lubbock, Texas, 79410, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

West Virginia University

Morgantown, West Virginia, 26506, United States

Location

Green Bay Oncology, Ltd. - St. Vincent Hospital

Green Bay, Wisconsin, 54301, United States

Location

MeSH Terms

Conditions

Colonic Neoplasms

Interventions

regorafenib

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases

Study Officials

• Norman Wolmark, MD

  NSABP Foundation

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 4, 2015
• First Posted: January 26, 2016
• Study Start: June 1, 2016
• Primary Completion: October 1, 2019
• Study Completion: October 1, 2019
• Last Updated: April 14, 2022

Record last verified: 2022-04

Locations

US (51)