Clinical trial NCT02425683 (phase 2, status: terminated)
Conditions: colorectal neoplasms, adenocarcinoma of the colon, adenocarcinoma of the rectum
ICD codes: C05.2, C10.0, C16.0, C16.4, C17.0, C17.1, C17.2, C22.0, C22.1, C4A.9, C7B.1, D09.9, C4A.0, C4A.31, C22.0, C22.1, C4A.9, C7B.1, D09.9, C4A.0, C4A.31
Drugs: regorafenib
SMILES: [H][N]1([H])[C@@H]2CCCC[C@H]2[N]([H])([H])[Pt]11OC(=O)C(=O)O1
Reason stopped: 
    insufficient accrual
  
Eligibility criteria:

        Inclusion Criteria:

          -  A signed Patient Authorization Form (HIPAA) has been obtained prior to registration

          -  Subjects must be able to understand and be willing to sign the written informed
             consent form. A signed informed consent form must be appropriately obtained prior to
             the conduct of any trial-specific procedure.

          -  Age ≥ 18 years.

          -  Stage IIIC colorectal cancer (T4a, N2a, M0) or (T3-4a, N2b, M0), or (T4b, N1- N2, M0)
             (per AJCC 7th ed).

          -  Must have started adjuvant FOLFOX chemotherapy within 8 weeks of resection for
             colorectal carcinoma

          -  CT scan that demonstrates no evidence of disease (NED) after completion of adjuvant
             therapy Note: This CT scan will also be used for Texture analysis.

          -  Received FOLFOX within 6 weeks before starting regorafenib

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-1

          -  Life expectancy of at least 12 weeks (3 months).

          -  Complete Metabolic Profile (CMP) within normal limits

          -  Adequate bone marrow, liver, and renal function as assessed by the following
             laboratory requirements:

               -  Total bilirubin ≤ 1.5 x the upper limits of normal (ULN)

               -  Alanine aminotransferase (ALT) and aspartate amino-transferase (AST) ≤ 2.5 x ULN

               -  Alkaline phosphatase limit ≤ 2.5 x ULN

               -  Lipase ≤ 1.5 x ULN

               -  Serum creatinine ≤ 1.5 x ULN

               -  International normalized ratio (INR)/ Partial thromboplastin time (PTT) ≤ 1.5 x
                  ULN. (Subjects who are prophylactically treated with an agent such as warfarin or
                  heparin will be allowed to participate provided that no prior evidence of
                  underlying abnormality in coagulation parameters exists. Close monitoring of at
                  least weekly evaluations will be performed until INR/PTT is stable based on a
                  measurement that is pre-dose as defined by the local standard of care.

               -  Platelet count ≥ 100,000 /mm3, hemoglobin (Hb) ≥ 9 g/dL, absolute neutrophil
                  count (ANC) ≥ 1500/mm3. Blood transfusion to meet the inclusion criteria will not
                  be allowed.

          -  Normal carcinoembryonic antigen (CEA) prior to study entry

          -  Glomerular filtration rate (GFR) ≥ 60 mL/min/1.73 m2 according to the Modified Diet in
             Renal Disease (MDRD) abbreviated formula.

          -  Women of childbearing potential must have a negative serum pregnancy test performed
             within 7 days prior to the start of study drug. Post-menopausal women (defined as no
             menses for at least 1 year) and surgically sterilized women are not required to
             undergo a pregnancy test. The definition of adequate contraception will be based on
             the judgment of the investigator.

          -  Subjects (men and women) of childbearing potential must agree to use adequate
             contraception beginning at the signing of the informed consent form (ICF) until at
             least 3 months after the last dose of study drug. The definition of adequate
             contraception will be based on the judgment of the principal investigator or a
             designated associate.

          -  Subject must be able to swallow and retain oral medication.

          -  Discretionary use of growth factors allowed

        Exclusion Criteria:

          -  Previous assignment to treatment during this study. Subjects permanently withdrawn
             from study participation will not be allowed to re-enter study.

          -  Uncontrolled hypertension (systolic pressure >140 mm Hg or diastolic pressure > 90 mm
             Hg [NCI-Common Toxicity Criteria for Adverse Effects (CTCAE) v4.03] on repeated
             measurement) despite optimal medical management.

          -  Evidence of remaining tumor

          -  Has local or distant metastasis

          -  Previous antiangiogenic treatment

          -  Abnormal hematological, renal, or liver function

          -  Impaired pulmonary function

          -  Evidence of ≥ Grade 2 neuropathy

          -  Active or clinically significant cardiac disease including:

               -  Congestive heart failure - New York Heart Association (NYHA) > Class II.

               -  Active coronary artery disease.

               -  Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or
                  digoxin.

               -  Unstable angina (anginal symptoms at rest), new-onset angina within 3 months
                  before randomization, or myocardial infarction within 6 months before
                  randomization.

          -  Evidence or history of bleeding diathesis or coagulopathy.

          -  Any hemorrhage or bleeding event ≥ NCI CTCAE Grade 3 within 4 weeks prior to start of
             study medication.

          -  Subjects with thrombotic, embolic, venous, or arterial events, such as cerebrovascular
             accident (including transient ischemic attacks), deep vein thrombosis, or pulmonary
             embolism within 6 months of start of study treatment.

          -  Subjects with any previously untreated or concurrent cancer that is distinct in
             primary site or histology from breast cancer except cervical cancer in-situ, treated
             basal cell carcinoma, or superficial bladder tumor. Subjects surviving a cancer that
             was curatively treated and without evidence of disease for more than 3 years before
             randomization are allowed. All cancer treatments must be completed at least 3 years
             prior to study entry (ie, signature date of the informed consent form).

          -  Patients with phaeochromocytoma.

          -  Known history of human immunodeficiency virus (HIV) infection or current chronic or
             active hepatitis B or C infection requiring treatment with antiviral therapy.

          -  Ongoing infection > Grade 2 NCI-CTCAE v4.03.

          -  Presence of a non-healing wound, non-healing ulcer, or bone fracture.

          -  Dehydration Grade ≥ 1 NCI-CTCAE v4.03.

          -  Patients with seizure disorder requiring medication.

          -  Persistent proteinuria ≥ Grade 3 NCI-CTCAE v4.03 (> 3.5 g/24 hrs, measured by urine
             protein: creatinine ratio on a random urine sample).

          -  Interstitial lung disease with ongoing signs and symptoms at the time of informed
             consent.

          -  Pleural effusion or ascites that causes respiratory compromise (≥ NCI-CTCAE version
             4.03 Grade 2 dyspnea).

          -  History of organ allograft (including corneal transplant).

          -  Known or suspected allergy or hypersensitivity to any of the study drugs, study drug
             classes, or excipients of the formulations given during the course of this trial.

          -  Any malabsorption condition.

          -  Women who are pregnant or breast-feeding.

          -  Any condition which, in the investigator's opinion, makes the subject unsuitable for
             trial participation.

          -  Substance abuse, medical, psychological or social conditions that may interfere with
             the subject's participation in the study or evaluation of the study results.

          -  Concurrent anti-cancer therapy (chemotherapy, radiation therapy, surgery,
             immunotherapy, biologic therapy, or tumor embolization) other than study treatment
             (regorafenib, other agents being investigated in combination with regorafenib).

          -  Prior use of regorafenib.

          -  Concurrent use of another investigational drug or device therapy (ie, outside of study
             treatment) during, or within 4 weeks of trial entry (signing of the informed consent
             form).

          -  Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
             before start of study medication.

          -  Therapeutic anticoagulation with Vitamin-K antagonists (eg, warfarin) or with heparins
             and heparinoids.

             o However, prophylactic anticoagulation as described below is allowed:

               -  Low dose warfarin (1 mg orally, once daily) with PT-INR ≤ 1.5 x ULN is permitted.
                  Infrequent bleeding or elevations in PT-INR have been reported in some subjects
                  taking warfarin while on regorafenib therapy. Therefore, subjects taking
                  concomitant warfarin should be monitored regularly for changes in PT, PT-INR, or
                  clinical bleeding episodes.

               -  Low dose aspirin (≤ 100 mg daily).

               -  Prophylactic doses of heparin.

          -  Use of any herbal remedy (eg, St. John's wort [Hypericum perforatum]) Note:
             Granulocyte colony-stimulating factor (G-CSF) and other hematopoietic growth factors
             may be used in the management of acute toxicity, such as febrile neutropenia, when
             clinically indicated or at the investigator's discretion. However, they may not be
             substituted for a required dose reduction. Subjects are permitted to take chronic
             erythropoietin.