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

NCT ID: NCT02664077

Last Updated: 2022-04-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE3

Total Enrollment

34 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-06-30

Study Completion Date

2019-10-31

Brief Summary

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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).

Detailed Description

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The primary aim of this study is to determine the value of regorafenib in improving DFS. The secondary aims are to evaluate the dose tolerance and long term toxicity of two years of regorafenib following standard adjuvant therapy, and to evaluate the effect of the use of regorafenib in overall survival (OS).

Eligible patients in this double-blind study will be randomized to take either regorafenib 120 mg or placebo orally, once daily for 21 consecutive days of a 28 day cycle for 26 cycles (2 years).

Accrual for this study will be approximately 1118 randomized patients. These 1118 patients will provide approximately 313 DFS events at the time of primary analysis. An initial futility analysis will be performed when 312 patients have been on study at least 3 months. The decision to continue the trial will be determined by success of both early stopping endpoints defined as follows:

* The toxicity profile of regorafenib compared to placebo is acceptable.
* The regorafenib regimen is tolerable for prolonged administration.

An estimated compliance rate of 60% at 6 months for regorafenib will be required for continuation of the study.

If toxicity is acceptable and compliance with regorafenib is at least 60% nominally, then accrual will continue.

The second futility analysis will be conducted when approximately 67 DFS events are observed. Trial conduct and accrual will continue unless the primary endpoint (DFS) trends too far in the opposite direction (hazard ratio greater than or equal to 1.1).

Toxicity will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

NSABP C-13 will include a Behavioral and Health Outcomes correlative science component. A C-13 Quality of Life (QOL) questionnaire will be administered at baseline (after consent and prior to randomization) and at 3 months, 6 months, 12 months, 18 months, 24 months, and 30 months.

Submission of blood samples for C-13 correlative science studies will be a study requirement for all patients. Submissions will also include archived primary tumor tissue from the resected colon primary. Blood samples for pharmacokinetics (PK) will be collected on Day 15 of Cycle 1 and Day 15 of Cycle 2, with additional blood samples for biomarkers collected at various time points for future analysis.

Conditions

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Stage III (IIIB or IIIC) Colon Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Group 1: Regorafenib

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

Group Type EXPERIMENTAL

Regorafenib

Intervention Type DRUG

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

Group 2: Placebo

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

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

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

Interventions

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Regorafenib

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

Intervention Type DRUG

Placebo

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

Intervention Type DRUG

Other Intervention Names

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Stivarga

Eligibility Criteria

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Inclusion Criteria

* 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.)
* Lipase performed within 28 days of randomization must be less than or equal to 1.5 x ULN for the lab.
* Serum creatinine performed within 28 days of randomization must be less than or equal to 1.5 x ULN for the lab.
* Urinalysis dipstick for urinary protein performed within 28 days prior to randomization must be 0-1+ protein. If urine dipstick result is greater than or equal to 2+ protein, a 24-hour urine protein must be less than 1.0 g/24 hours.
* Glomerular filtration rate (GFR) must be greater than or equal to 30 mL/min/1.73 m2 according to the Modified Diet in Renal Disease (MDRD) abbreviated formula.
* International normalized ratio of prothrombin time must be less than or equal to 1.5 times the ULN. Patients who are therapeutically treated with an agent such as warfarin or heparin will be allowed to participate if no underlying abnormality in coagulation parameters exists per medical history.
* Patients (male or female) of reproductive potential must agree to use an effective method of contraception (as discussed with treating physician) from the time consent is signed, during study therapy, and for at least 90 days after the last dose of study therapy.
* Patients with prior malignancies are eligible if they have been disease-free for at least 5 years and are deemed by their physician to be at low risk for recurrence. Patients with squamous or basal cell carcinoma of the skin, melanoma in situ, carcinoma in situ of the cervix, or carcinoma in situ of the colon or rectum that have been effectively treated are eligible, even if these conditions were diagnosed within 5 years of randomization.

Exclusion Criteria

* 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;
* myocardial infarction within 6 months prior to randomization;
* unstable angina (angina symptoms at rest) within less than or equal to 3 months prior to randomization; and
* clinically significant symptomatic arrhythmia despite anti-arrhythmic therapy.
* Uncontrolled blood pressure (systolic pressure greater than 150 mmHg or diastolic pressure greater than 90 mmHg on repeated measurements).
* Symptomatic brain or meningeal tumors.
* Patients with seizure disorder requiring medication.
* Presence of non-healing wound, non-healing ulcer, or bone fracture.
* Symptomatic interstitial lung disease or definitive evidence of interstitial lung disease described on CT scan, MRI, or chest x-ray in asymptomatic patients; dyspnea at rest requiring current continuous oxygen.
* Arterial or venous thrombotic or embolic events such as cerebral vascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 6 months before randomization (except for adequately treated catheter-related venous thrombosis occurring within 6 months before randomization).
* Symptomatic peripheral ischemia.
* Psychiatric or addictive disorders or other conditions or unresolved toxicities of prior therapy greater than grade 2 that, in the opinion of the investigator, would preclude the patient from meeting the study requirements, or interfere with interpretation of study results.
* Pregnancy or lactation at the time of study entry. (Note: Pregnancy testing must be performed within 14 days prior to randomization according to institutional standards for women of childbearing potential.)
* Major surgery (including ostomy reversal), open biopsy or significant trauma injury, within 28 days prior to randomization.
* Anticipation of need for major surgical procedures during the course of study.
* Known hypersensitivity to study drug, study drug classes or excipients of the formulation.
* Use of any vascular endothelial growth factor (VEGF) targeted therapy or previous use of regorafenib.
* Patients taking strong inducers or inhibitors of cytochrome P450 3A4 (CYP3A4) who cannot interrupt therapy from the time the C-13 consent is signed through 30 days after the last dose of study therapy.
* Patients taking herbal remedies (e.g., St. John's Wort \[Hypericum perforatum\]) who cannot interrupt therapy from the time the C-13 consent is signed through 30 days after the last dose of study therapy.
* Use of immune modulators and/or any immunosuppressive drugs.
* Use of any investigational agent within 28 days of randomization.
* Patients receiving erythropoiesis-stimulating agents or other hematopoietic growth factors.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Bayer

INDUSTRY

Sponsor Role collaborator

NSABP Foundation Inc

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Norman Wolmark, MD

Role: PRINCIPAL_INVESTIGATOR

NSABP Foundation

Locations

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St. Joseph Hospital of Orange

Orange, California, United States

Site Status

St. Joseph Heritage Healthcare

Santa Rosa, California, United States

Site Status

Kaiser Permanente Medical Center - Vallejo

Vallejo, California, United States

Site Status

Colorado Cancer Research Program

Denver, Colorado, United States

Site Status

Yale University

New Haven, Connecticut, United States

Site Status

University of Florida

Gainesville, Florida, United States

Site Status

Mount Sinai Comprehensive Cancer Center

Miami Beach, Florida, United States

Site Status

Memorial Health University Medical Center

Savannah, Georgia, United States

Site Status

Cancer Care Specialists of Illinois - Decatur Memorial Hospital

Decatur, Illinois, United States

Site Status

Edward Hospital Cancer Center

Naperville, Illinois, United States

Site Status

Carle Cancer Center

Urbana, Illinois, United States

Site Status

Northern Indiana Cancer Research Consortium

South Bend, Indiana, United States

Site Status

Oncology Associates at Mercy Medical Center

Cedar Rapids, Iowa, United States

Site Status

Genesis Medical Center - West Campus

Davenport, Iowa, United States

Site Status

University of Iowa

Iowa City, Iowa, United States

Site Status

Covenant Cancer Treatment Center

Waterloo, Iowa, United States

Site Status

Norton Cancer Institute, Norton Healthcare Pavilion

Louisville, Kentucky, United States

Site Status

Tulane University Health Sciences Center

New Orleans, Louisiana, United States

Site Status

New England Cancer Specialists

Scarborough, Maine, United States

Site Status

Berkshire Medical Center Cancer and Infusion Center

Pittsfield, Massachusetts, United States

Site Status

Breslin Cancer Center

Lansing, Michigan, United States

Site Status

Metro Minnesota Community Oncology Research Consortium

Saint Louis Park, Minnesota, United States

Site Status

Missouri Valley Cancer Consortium

Omaha, Nebraska, United States

Site Status

Nevada Cancer Research Foundation, Inc.

Las Vegas, Nevada, United States

Site Status

MD Anderson Cancer Center at Cooper

Camden, New Jersey, United States

Site Status

Monmouth Medical Center

Long Branch, New Jersey, United States

Site Status

Newark Beth Israel Medical Center

Newark, New Jersey, United States

Site Status

Community Medical Center

Toms River, New Jersey, United States

Site Status

Waverly Hematology Oncology

Cary, North Carolina, United States

Site Status

CaroMont Regional Medical Center

Gastonia, North Carolina, United States

Site Status

Margaret R. Pardee Memorial Hospital

Hendersonville, North Carolina, United States

Site Status

First Health of the Carolinas Cancer Center

Pinehurst, North Carolina, United States

Site Status

Wake Forest Baptist Health

Winston-Salem, North Carolina, United States

Site Status

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

Columbus, Ohio, United States

Site Status

Toledo Clinic Cancer Center

Toledo, Ohio, United States

Site Status

Abington Hospital -Jefferson South

Abington, Pennsylvania, United States

Site Status

Penn State Cancer Institute at Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

Site Status

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, United States

Site Status

Allegheny General Hospital

Pittsburgh, Pennsylvania, United States

Site Status

UPMC Cancer Centers

Pittsburgh, Pennsylvania, United States

Site Status

Guthrie Medical Group, PC

Sayre, Pennsylvania, United States

Site Status

Scranton Hematology Oncology

Scranton, Pennsylvania, United States

Site Status

Reading Hospital - McGlinn Cancer Institute

West Reading, Pennsylvania, United States

Site Status

AnMed Health Cancer Center

Anderson, South Carolina, United States

Site Status

McLeod Cancer Center for Treatment and Research

Florence, South Carolina, United States

Site Status

Wellmont Medical Associates Oncology and Hematology

Kingsport, Tennessee, United States

Site Status

Thompson Cancer Survival Center

Knoxville, Tennessee, United States

Site Status

Joe Arrington Cancer Research and Treatment Center

Lubbock, Texas, United States

Site Status

Virginia Commonwealth University

Richmond, Virginia, United States

Site Status

West Virginia University

Morgantown, West Virginia, United States

Site Status

Green Bay Oncology, Ltd. - St. Vincent Hospital

Green Bay, Wisconsin, United States

Site Status

Countries

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United States

Other Identifiers

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17808

Identifier Type: OTHER

Identifier Source: secondary_id

NSABP C-13

Identifier Type: -

Identifier Source: org_study_id

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