Clinical trial NCT02664077 (phase 3, status: terminated)
Conditions: stage iii (iiib or iiic) colon cancer
ICD codes: C18.2, C18.4, C18.6, C18.7, C18.9, D12.2, D12.3
Drugs: regorafenib, placebo
SMILES: [H][N]1([H])[C@@H]2CCCC[C@H]2[N]([H])([H])[Pt]11OC(=O)C(=O)O1, CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
Reason stopped: 
    due to the significantly lower than expected accrual it was impossible to evaluate the endpoint
    in a timely fashion.
  
Eligibility criteria:

        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.