Sorafenib Plus Capecitabine (SorCape) in Previously Treated Metastatic Colorectal Cancer
Condition: Colorectal Cancer Metastatic
MeSH terms: Colorectal Neoplasms
Intervention: Sorafenib Plus Capecitabine (SorCape)
Intervention description: Sorafenib 200-400 mg PO twice daily on days 1-21 (dose escalation schema) plus Capecitabine 1000 mg/m2 PO twice daily on days 1-14 repeated every 21 days
Intervention MeSH terms: Capecitabine; Sorafenib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 43.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Metastatic; Colon Cancer; Rectal Cancer

Summary:

      Combining Sorafenib with standard cytotoxic fluoropyrimidine therapy for advanced colorectal
      cancer may provide clinical benefit when no other treatment remains.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically proven adenocarcinoma of the colon or rectum.

          -  Metastatic disease that is not amenable to potentially curative treatment.

          -  Measurable disease (as per RECIST 1.1 criteria).

          -  At least one prior chemotherapeutic regimen for metastatic disease. Patients must have
             progressed following oxaliplatin based therapy (in either the adjuvant or metastatic
             setting) and irinotecan based therapy (in the metastatic setting).

          -  Adequate bone marrow, liver and renal function.

          -  Patients receiving anti-coagulation treatment with an agent such as warfarin or
             heparin may be allowed to participate, provided stability in anticoagulation therapy
             is documented at the treating provider's discretion. For patients on warfarin, the INR
             should be measured prior to the initiation of study treatment and should be monitored
             at least weekly, or as defined by the local standard of care, until INR is stable.

          -  Women of childbearing potential must have a negative serum pregnancy test performed
             within 7 days prior to the start of treatment.

          -  Women of childbearing potential and men must agree to use adequate contraception
             (barrier method of birth control) prior to study entry and for the duration of study
             participation. Men should use adequate birth control for at least three months after
             the last administration of sorafenib.

          -  Patients may have had a history of other (non-colorectal) malignancies if there is no
             current evidence of persistent or recurrent disease and they are not undergoing any
             active therapy (including hormonal).

          -  Patients should have paraffin-embedded tissue from initial diagnosis or prior
             colorectal cancer surgery available for molecular analysis.

          -  Patients must consent to participate in the study and must have signed and dated an
             IRB-approved consent form conforming to federal and institutional guidelines. Consent
             must be obtained prior to any study specific procedures.

        Exclusion Criteria:

          -  Prior therapy with a tyrosine kinase inhibitor.

          -  Age < 18 years

          -  ECOG Performance Status > 2

          -  Less than 28 days elapsed from prior radiation therapy, surgery or chemotherapy to the
             time of registration.

          -  History of known brain metastasis. Patients with neurological symptoms must undergo a
             CT scan/MRI of the brain to exclude brain metastasis.

          -  History of clinically significant cardiac disease (severe/unstable angina pectoris,
             NYHA class III or IV congestive heart failure, symptomatic coronary artery disease) or
             myocardial infarction, cerebrovascular accident or transient ischemic attack within
             the last 12 months.

          -  Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy. Uncontrolled
             hypertension defined as systolic blood pressure > 140 mmHg or diastolic pressure > 90
             mmHg, as measured on 3 consecutive pre-enrollment assessments, despite optimal medical
             management.

          -  Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C.

          -  Active clinically serious infection > CTCAE Grade 2.

          -  Pulmonary hemorrhage/bleeding event > CTCAE Grade 2 within 4 weeks of first dose of
             study drug.

          -  Any other hemorrhage/bleeding event > CTCAE Grade 3 within 4 weeks of first dose of
             study drug.

          -  Pulmonary embolism or any other uncontrolled thromboembolic event within 3 months
             prior to registration or occurrence of deep vein thrombosis within 4 weeks of
             registration.

          -  Serious non-healing wound, ulcer, or bone fracture.

          -  Evidence or history of a clinically significant bleeding diathesis or coagulopathy
             (without vitamin K antagonist therapy).

          -  Use of St. John's Wort or rifampin (rifampicin).

          -  Known or suspected allergy to sorafenib or capecitabine.

          -  Any condition that impairs patient's ability to swallow whole pills.

          -  Any known malabsorption problem.

          -  History of chronic or inflammatory bowel disorders, clinically significant chronic
             diarrhea refractory to medical management, or unresolved bowel obstruction.