Clinical trial NCT00536575 (phase 1/phase 2, status: completed)
Conditions: multiple myeloma
ICD codes: C90.01, C90.02, C90.00
Drugs: bortezomib, sorafenib
SMILES: ClCCN(CCCl)P1(=O)NCCCO1, CNC(=O)C1=NC=CC(OC2=CC=C(NC(=O)NC3=CC(=C(Cl)C=C3)C(F)(F)F)C=C2)=C1
Eligibility criteria:

        Inclusion Criteria:

          -  Eligible participants must have been previously diagnosed using standard criteria and
             have received no more than 2 prior regimens for the treatment of multiple myeloma.

          -  Participant must be defined as Relapsed or Refractory Disease by one of the following
             criteria prior to enrollment: Relapsed Disease after high-dose therapy (autologous
             stem cell transplantation) as part of the first-line line treatment program. These
             patients may have received a maximum of 1 previous regimen, Refractory Disease or
             Relapsed Disease after > 1 prior therapy for multiple myeloma. Prior bortezomib
             treatment permitted if the patient achieved a documented response.

          -  ECOG performance status 0, 1, or 2.

          -  WBC >= 3000; ANC >= 1000; platelets >= 50,000 (Patients with platelets >= 30,000 are
             eligible if thrombocytopenia is felt to be due to extensive bone marrow involvement
             with myeloma).

          -  Serum creatinine < 2.0 mg/dL for a calculated or measured creatinine clearance > 30
             mL/minute

          -  Total bilirubin < 1.5 x ULN

          -  ALT and AST < 2.5 x the ULN ( < 5 x ULN for patients with liver involvement)

          -  INR < 1.5 or a PT/PTT within normal limits. Patients receiving anti-coagulation
             treatment with an agent such as warfarin or heparin may be allowed to participate. For
             patients on warfarin, the INR should be measured prior to initiation of sorafenib and
             monitored at least weekly, or as defined by the local standard of care, until INR is
             stable.

          -  Patients must have measurable or evaluable disease. In patients with disease limited
             to bone and bone marrow, serial paraprotein measurements are acceptable for evaluable
             disease.

        Exclusion Criteria:

          -  Patients with > grade 1 peripheral neuropathy.

          -  Thrombolic or embolic events such as a cerebrovascular accident, including transient
             ischemic attacks, within the past 6 months.

          -  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.

          -  Known brain metastasis. Patients with neurological symptoms must undergo CT scan/MRI
             of the brain to exclude brain metastasis.

          -  Patients with other medical conditions that would potentially interfere with their
             participation in this trial.

          -  Patients with other active malignancies, or history of treatment for other invasive
             cancers, within 3 years of study entry.

          -  Patients with previous evidence of hypersensitivity to sorafenib, bortezomib, boron,
             or mannitol.

          -  Women who are pregnant or lactating are ineligible. All patients of childbearing
             potential are required to use adequate methods of contraception while receiving study
             treatment, and for at least 2 weeks after the last dose of sorafenib. Men should
             continue to use contraception until at least 3 months after their last dose of
             sorafenib.

          -  Evidence of POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal
             gammopathy, and skin changes) syndrome.

          -  Cardiac disease: Congestive heart failure > class II NYHA (see Appendix D.) Patients
             must not have unstable angina (anginal symptoms at rest), new onset angina (began
             within the last 3 months), or myocardial infarction within the past 6 months.

          -  Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.

          -  Uncontrolled hypertension defined as systolic blood pressure > 150 mmHg or diastolic
             pressure > 90 mmHg, despite optimal medical management.

          -  Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C.

          -  Active clinically serious infection > CTCAE Grade 2.