Lower or Standard Dose Regorafenib in Treating Patients With Refractory Metastatic Colorectal Cancer
Condition: Colon Adenocarcinoma; Rectal Adenocarcinoma; Stage III Colorectal Cancer AJCC v7; Stage IIIA Colorectal Cancer AJCC v7; Stage IIIB Colorectal Cancer AJCC v7; Stage IIIC Colorectal Cancer AJCC v7; Stage IV Colorectal Cancer AJCC v7; Stage IVA Colorectal Cancer AJCC v7; Stage IVB Colorectal Cancer AJCC v7
MeSH terms: Colorectal Neoplasms; Adenocarcinoma; Colonic Neoplasms
Intervention: Clobetasol Propionate; Pharmacological Study; Quality-of-Life Assessment; Regorafenib
Intervention description: Given topically; Correlative studies; Ancillary studies; Given PO
Intervention MeSH terms: Clobetasol
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 123.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase II trial studies how well lower-dose compared to standard dose
      regorafenib works in treating patients with colorectal cancer that has spread from the
      primary site (place where it started) to other places in the body and does not respond to
      treatment. Regorafenib may stop the growth of colorectal cancer by blocking the growth of new
      blood vessels necessary for tumor growth and by blocking some of the enzymes needed for cell
      growth. It is not yet known whether lower-dose or standard dose regorafenib is more effective
      in treating patients with colorectal cancer. Clobetasol propionate is a steroid cream that is
      commonly used to treat a variety of skin conditions and may help prevent hand-foot skin
      reactions in patients receiving regorafenib.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histological or cytological documentation of adenocarcinoma of the colon or rectum

          -  Advanced or metastatic colorectal cancer with no curative options available and
             progression on previous standard therapy, including an EGFR inhibitor if KRAS
             wild-type

          -  Measurable or non-measurable disease

          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1

          -  Life expectancy of >= 3 months

          -  Absolute neutrophil count (ANC) > 1500/mm^3 (obtained =< 7 days prior to
             randomization)

          -  Platelet count > 100,000/mm^3 (obtained =< 7 days prior to randomization)

          -  Hemoglobin > 9.0 g/dL (obtained =< 7 days prior to randomization)

          -  Total bilirubin =< 1.5 x upper limit of normal (ULN) (obtained =< 7 days prior to
             randomization)

          -  Alanine aminotransferase (ALT) and aspartate amino-transferase (AST) =< 2.5 x ULN (=<
             5 x ULN for subjects with liver involvement of their cancer) (obtained =< 7 days prior
             to randomization)

          -  Serum creatinine =< 1.5 x ULN (obtained =< 7 days prior to randomization)

          -  International normalized ratio (INR)/partial thromboplastin time (PTT) =< 1.5 x ULN
             (obtained =< 7 days prior to randomization)

               -  NOTE: patients who are therapeutically 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

          -  Alkaline phosphatase limit =< 2.5 x ULN (=< 5 x ULN for patients with liver
             involvement of their cancer) (obtained =< 7 days prior to randomization)

          -  Negative serum pregnancy test done =< 7 days prior to randomization, for women of
             childbearing potential only; note: 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

          -  Ability to complete questionnaire(s) by themselves or with assistance

          -  Provide informed written consent

          -  Willing to return to enrolling institution for follow-up (during the active monitoring
             phase of the study)

          -  Willing to provide blood samples for correlative research and banking purposes

        Exclusion Criteria:

          -  Prior treatment with regorafenib

          -  Major surgical procedure, open biopsy, or significant traumatic injury =< 28 days
             prior to randomization

          -  Congestive heart failure > New York Heart Association (NYHA) class 2

          -  Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3
             months) or myocardial infarction less than 6 months prior to randomization

          -  Cardiac arrhythmias requiring anti-arrhythmic therapy; Note: pace makers, beta
             blockers, or digoxin are permitted

          -  Uncontrolled hypertension; (systolic blood pressure > 140 mmHg or diastolic pressure >
             90 mmHg despite optimal medical management)

          -  History of or current pheochromocytoma

          -  Arterial or venous thrombotic or embolic events such as cerebrovascular accident
             (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism =<
             6 months prior to randomization

          -  Ongoing infection > grade 2 National Cancer Institute (NCI)-Common Terminology
             Criteria for Adverse Events (CTCAE) version 4.0

          -  Known history of chronic hepatitis B or C

          -  Patients with seizure disorder requiring medication

          -  Symptomatic metastatic brain or meningeal tumors unless the patient is > 6 months from
             definitive therapy, has a negative imaging study within 4 weeks of randomization and
             is clinically stable with respect to the tumor at the time of randomization; note:
             patient must not be undergoing acute steroid therapy or taper (chronic steroid therapy
             is acceptable provided that the dose is stable for one month prior to and following
             screening radiographic studies)

          -  History of organ allograft (including corneal transplant)

          -  Evidence or history of bleeding diathesis or any hemorrhage or bleeding event > CTCAE
             grade 3 =< 4 weeks prior to randomization

          -  Non-healing wound, ulcer, or bone fracture

          -  Renal failure requiring hematological (hemo-) or peritoneal dialysis

          -  Dehydration CTCAE (version 4.0) grade >= 1

          -  Substance abuse, medical, psychological or social conditions that may interfere with
             the patient?s participation in the study or evaluation of the study results

          -  Known hypersensitivity to any of the study drugs, study drug classes, or excipients in
             the formulation

          -  Interstitial lung disease with ongoing signs and symptoms at the time of informed
             consent

          -  Persistent proteinuria of Common Toxicity Criteria (CTC) grade 3 or higher (>= 3.5
             g/24 hours [hrs])

          -  Patients unable to swallow oral medications

          -  Any malabsorption condition

          -  Unresolved toxicity greater than CTCAE (version 4.0) grade 1 attributed to any prior
             therapy/procedure excluding alopecia and oxaliplatin induced neurotoxicity =< grade 2

          -  Albumin levels < 2.5 g/dl

          -  Any of the following:

               -  Pregnant women

               -  Nursing women

               -  Men or women of childbearing potential who are unwilling to employ adequate
                  contraception

                    -  NOTE: 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

          -  Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment
             of the investigator, would make the patient inappropriate for entry into this study or
             interfere significantly with the proper assessment of safety and toxicity of the
             prescribed regimens

          -  Immunocompromised patients and patients known to be human immunodeficiency virus (HIV)
             positive and currently receiving antiretroviral therapy; NOTE: patients known to be
             HIV positive, but without clinical evidence of an immunocompromised state, are
             eligible for this trial

          -  Receiving any other investigational agent which would be considered as a treatment for
             the primary neoplasm

          -  Previous or concurrent cancer that is distinct in primary site or histology from
             colorectal cancer within 3 years prior to randomization EXCEPT for curatively treated
             cervical cancer in situ, non-melanoma skin cancer and superficial bladder tumors (Ta
             [non-invasive tumor], Tis [carcinoma in situ] and T1 [tumor invades lamina propria]);
             note: all cancer treatments for cancers that were distinct in a primary site other
             than colorectal must be completed at least 3 years prior to randomization (i.e.,
             signature date of the informed consent form)

          -  Pleural effusion or ascites that causes respiratory compromise (>= CTCAE version 4.0
             grade 2 dyspnea)

          -  Concurrent anti-cancer therapy =< 4 weeks from registration (chemotherapy, radiation
             therapy, surgery, immunotherapy, biologic therapy, or tumor embolization)

          -  Current use of clobetasol propionate

          -  Use of any herbal remedy (e.g. St. John?s wort [Hypericum perforatum])

          -  Patients unable to ambulate or who have amputations or paralysis of any extremity

          -  History of contact dermatitis to clobetasol propionate or similarly fluorinated
             steroids or other steroids with the propionate ester