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Stage III (IIIB or IIIC) Colon CancerPhase 3ARGONCT02664077

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

A Phase 3 study testing Regorafenib in people with Stage III (IIIB or IIIC) Colon Cancer, run by NSABP Foundation Inc at 51 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Stage III (IIIB or IIIC) Colon Cancer
What is being tested?
Regorafenib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
34 participants
Where
51 sitesUnited States
Study dates
Jun 2016to Oct 2019
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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).
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  • 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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

51 sites in 1 country.

51 sites in 1 country

United States51 sites

  • Abington Hospital -Jefferson South

    Abington, Pennsylvania, 19001

  • AnMed Health Cancer Center

    Anderson, South Carolina, 29621

  • MD Anderson Cancer Center at Cooper

    Camden, New Jersey, 08103

  • Waverly Hematology Oncology

    Cary, North Carolina, 27511

  • Oncology Associates at Mercy Medical Center

    Cedar Rapids, Iowa, 52403

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

    Columbus, Ohio, 43210

  • Genesis Medical Center - West Campus

    Davenport, Iowa, 52804

  • Cancer Care Specialists of Illinois - Decatur Memorial Hospital

    Decatur, Illinois, 62526

  • Colorado Cancer Research Program

    Denver, Colorado, 80222

  • McLeod Cancer Center for Treatment and Research

    Florence, South Carolina, 29502

  • University of Florida

    Gainesville, Florida, 32610

  • CaroMont Regional Medical Center

    Gastonia, North Carolina, 28054

  • Green Bay Oncology, Ltd. - St. Vincent Hospital

    Green Bay, Wisconsin, 54301

  • Margaret R. Pardee Memorial Hospital

    Hendersonville, North Carolina, 28791

  • Penn State Cancer Institute at Milton S. Hershey Medical Center

    Hershey, Pennsylvania, 17033-0850

  • University of Iowa

    Iowa City, Iowa, 52242

  • Wellmont Medical Associates Oncology and Hematology

    Kingsport, Tennessee, 37660

  • Thompson Cancer Survival Center

    Knoxville, Tennessee, 37916

  • Breslin Cancer Center

    Lansing, Michigan, 48910

  • Nevada Cancer Research Foundation, Inc.

    Las Vegas, Nevada, 89106

  • Monmouth Medical Center

    Long Branch, New Jersey, 07740-6395

  • Norton Cancer Institute, Norton Healthcare Pavilion

    Louisville, Kentucky, 40202

  • Joe Arrington Cancer Research and Treatment Center

    Lubbock, Texas, 79410

  • Mount Sinai Comprehensive Cancer Center

    Miami Beach, Florida, 33140

  • West Virginia University

    Morgantown, West Virginia, 26506

  • Edward Hospital Cancer Center

    Naperville, Illinois, 60540-7499

  • Yale University

    New Haven, Connecticut, 06510

  • Tulane University Health Sciences Center

    New Orleans, Louisiana, 70112

  • Newark Beth Israel Medical Center

    Newark, New Jersey, 07112

  • Missouri Valley Cancer Consortium

    Omaha, Nebraska, 68106

  • St. Joseph Hospital of Orange

    Orange, California, 92868

  • Thomas Jefferson University Hospital

    Philadelphia, Pennsylvania, 19107

  • First Health of the Carolinas Cancer Center

    Pinehurst, North Carolina, 28374

  • Allegheny General Hospital

    Pittsburgh, Pennsylvania, 15212

  • UPMC Cancer Centers

    Pittsburgh, Pennsylvania, 15232

  • Berkshire Medical Center Cancer and Infusion Center

    Pittsfield, Massachusetts, 01201

  • Virginia Commonwealth University

    Richmond, Virginia, 23298

  • Metro Minnesota Community Oncology Research Consortium

    Saint Louis Park, Minnesota, 55416

  • St. Joseph Heritage Healthcare

    Santa Rosa, California, 95403

  • Memorial Health University Medical Center

    Savannah, Georgia, 31404

  • Guthrie Medical Group, PC

    Sayre, Pennsylvania, 18840

  • New England Cancer Specialists

    Scarborough, Maine, 04074

  • Scranton Hematology Oncology

    Scranton, Pennsylvania, 18510

  • Northern Indiana Cancer Research Consortium

    South Bend, Indiana, 46628

  • Toledo Clinic Cancer Center

    Toledo, Ohio, 43623

  • Community Medical Center

    Toms River, New Jersey, 08755

  • Carle Cancer Center

    Urbana, Illinois, 61801

  • Kaiser Permanente Medical Center - Vallejo

    Vallejo, California, 94589

  • Covenant Cancer Treatment Center

    Waterloo, Iowa, 50702

  • Reading Hospital - McGlinn Cancer Institute

    West Reading, Pennsylvania, 19611

  • Wake Forest Baptist Health

    Winston-Salem, North Carolina, 27157

Other trials in United States

About this study

Official title: A Phase III Randomized Placebo-Controlled Study Evaluating Regorafenib Following Completion of Standard Chemotherapy for Patients With Stage III Colon Cancer

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).

Read the detailed description

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.

Being tested
Regorafenib, Placebo
Keywords
NSABP, Colon cancer, Regorafenib, Stage III, Adjuvant therapy
Medical subject headings
Colonic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RegorafenibDrug

    Also called Stivarga

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

  • PlaceboDrug

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

Study groups in NCT02664077
Study groupRoleWhat they receive
Group 1: RegorafenibExperimentalPatients receive regorafenib orally once daily for 21 days of a 28 day cycle for a total of 26 cycles.
Receives: Drug: Regorafenib
Group 2: PlaceboPlacebo comparatorPatients receive placebo orally once daily for 21 days of a 28 day cycle for a total of 26 cycles.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

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

Secondary outcomes (7)

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

    Determine the overall Survival

    Measured: 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)

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

    Evaluate toxicity associated with study therapy

    Measured: Every study visit through 30 days following study therapy

  3. Compliance - Time to discontinuation of study therapy.

    Evaluate the overall tolerability and compliance with study therapy

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

  4. Correlative Science - Biomarker evaluations

    Explore molecular and genetic correlatives for the degree of benefit from regorafenib

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

  5. Correlative Science - Pharmacokinetics - Plasma regorafenib concentrations

    Evaluation of exposure to regorafenib

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

  6. Correlative Science - Pharmacodynamics

    Evaluation of relationship between plasma concentrations and/or dose, efficacy, or adverse events

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

  7. Compare the symptoms experienced by patients receiving regorafenib to patients receiving placebo during treatment as measured by Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)

    Severity of treatment related symptoms experienced by patients.

    Measured: Baseline, 3 months, 6 months, 12 months, 18 months, 24 months and 6 months after discontinuation of protocol therapy

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Jan 2016 (estimated)
  2. Study startJun 2016
  3. Primary completionOct 2019
  4. Study completionOct 2019

Why it stopped: Due to the significantly lower than expected accrual it was impossible to evaluate the endpoint in a timely fashion.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
34 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02664077
Sponsor's protocol ID
NSABP C-13
Other IDs
17808
Acronym
ARGO
Status last verified
Apr 2022
First submitted
4 Dec 2015
Last updated
14 Apr 2022
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Regorafenib in people with Stage III (IIIB or IIIC) Colon Cancer, run by NSABP Foundation Inc at 51 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 22 inclusion and 36 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 14 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 51 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Due to the significantly lower than expected accrual it was impossible to evaluate the endpoint in a timely fashion.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Disease-free survival (DFS) - time from randomization until first colon cancer recurrence, second primary colon cancer, or death due to any cause. (time frame: Beginning at day 1 of cycle 3 (each cycle = 28 days) and every 6 months until study closure about 10 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02664077.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Apr 2022.

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