Pharmacokinetics and Safety of Regorafenib (BAY73-4506) in Cancer Subjects With Severe Renal Impairment
Condition: Neoplasms
MeSH terms: Renal Insufficiency
Intervention: Regorafenib (Stivarga, BAY73-4506)
Intervention description: Regorafenib 160 mg o.d. will be administered as a single dose on Day 1 of Stage 1 followed by multiple dosing in an intermittent administration schedule (3 week-on/1 week-off) over 2 cycles in Stage 2 (56 days, cycle defined as 28 days)
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 24.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Regorafenib; pharmacokinetics; safety; severe renal impairment; Solid tumors

Summary:

      To characterize the pharmacokinetics and safety of regorafenib in cancer subjects with severe
      renal impairment when compared to the Control group (cancer subjects with normal or mildly
      impaired renal function)
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subjects with histologically confirmed, locally advanced or metastatic, refractory
             solid tumors who are not candidates for standard therapy

          -  Male or female subject ≥ 18 years of age

          -  Women of childbearing potential must have a negative urine pregnancy test performed
             within 7 days before start of study treatment

          -  Life expectancy at least 8 weeks

          -  Adequate bone marrow, and liver function as assessed by the following laboratory
             requirements conducted within 7 days of starting the study treatment

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2

          -  For subjects with NORMAL OR MILDLY IMPAIRED RENAL FUNCTION (Control group); to be
             tested within 7 days of starting the study treatment:

               -  Estimated creatinine clearance (CLcr) ≥ 60 mL/min as calculated using the
                  Cockcroft-Gault equation

          -  For subjects with SEVERELY IMPAIRED renal function; to be tested within 7 days of
             starting the study treatment:

               -  CLcr 15-29 mL/min as calculated using the Cockcroft-Gault equation

        Exclusion Criteria:

          -  Symptomatic metastatic brain or meningeal tumors

          -  Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
             before start of study medication

          -  History of organ allograft

          -  Non-healing wound, skin ulcer, or bone fracture

          -  Pheochromocytoma

          -  Uncontrolled concurrent medical illness including uncontrolled hypertension

          -  History of cardiac disease

          -  Pleural effusion or ascites that causes respiratory compromise

          -  Interstitial lung disease with ongoing signs and symptoms at the time of screening

          -  Arterial or venous thrombotic or embolic events such as cerebrovascular accident
             (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism
             within 6 months before the start of study medication

          -  Subjects with evidence or history of bleeding diathesis; any hemorrhage or bleeding
             event NCI-CTCAE Grade ≥ 3 or higher within 4 weeks of start of investigational
             treatment

          -  Dehydration NCI-CTCAEversion 4.0 Grade ≥ 1

          -  Unresolved toxicity higher than NCI-CTCAE version 4.0 Grade 1 attributed to any prior
             therapy/procedure (excluding alopecia or anemia or grade 2 neuropathy that is not
             reversible due to oxaliplatin)

          -  Seizure disorder requiring anticonvulsant therapy (such as steroids or
             anti-epileptics)

          -  For subjects with SEVERELY IMPAIRED renal function:

               -  Renal failure requiring hemo- or peritoneal dialysis

               -  Acute renal failure

               -  Acute nephritis

               -  Nephrotic syndrome