Clinical trial NCT01078961 (phase 1, status: completed)
Conditions: melanoma
ICD codes: C43.0, C43.31, D03.9, C43.51, C43.9, D03.0, C43.4
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:

          -  Histological or cytological confirmation of malignant melanoma that is metastatic or
             unresectable

          -  Measurable disease, defined as at least one lesion that can be accurately measured in
             at least one dimension as 10mm or greater with spiral CT scan

          -  Patients may have received up to 4 prior treatments for their disease including
             immunotherapies such as high-dose interleukin 2 and antibodies directed against the
             human cytotoxic T-lymphocyte antigen 4

          -  18 years of age or older

          -  Life expectancy of greater than three months

          -  ECOG Performance status of 0 or 1

          -  Adequate organ and marrow function as outlined in the protocol

          -  Women of childbearing potential must have a negative serum pregnancy test performed
             within 7 days prior to the start of treatment

          -  INT < 1.5 or a PT/PTT within normal limits. Patients receiving anti-coagulation
             treatment wih 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

          -  Women of child-bearing potential and men must agree to use adequate contraception
             prior to study entry and for the duration of study participation.

        Exclusion Criteria:

          -  Chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C)
             prior to entering the study or those who have not recovered from adverse events dur to
             agents administered more than 4 weeks earlier

          -  Participants may not be receiving any other study agents

          -  Known, active CNS disease, including primary brain tumor, seizures not controlled with
             standard medical therapy, any unstable or untreated brain metastasis, or history of
             stroke within the past 12 months

          -  Prior therapy with bortezomib, sorafenib, or other proteasome inhibitor

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to sorafenib and bortezomib

          -  Participants receiving any medications or substances that are inducers of CYP3A4

          -  Known cardiac disease including congestive heart failure > class II NHYA, unstable
             angina or new onset angina, myocardial infarction within the past 6 months, or
             electrocardiographic evidence of acute ischemic or active conduction system
             abnormalities. Prior to study entry, any ECG abnormality at screening has to be
             documented by the investigator as not medically relevant

          -  Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy

          -  Uncontrolled intercurrent illness

          -  Pregnant women

          -  Individuals with a history of a different malignancy are ineligible except for the
             circumstances outlined in the protocol

          -  HIV-positive individuals on combination antiretroviral therapy

          -  Uncontrolled hypertension despite optimal medical management

          -  Thrombolic or embolic events

          -  Pulmonary hemorrhage/bleeding event CTCAE Grade 2 or greater within 4 weeks of first
             dose of study drug

          -  Any other hemorrhage/bleeding event CTCAE Grade 3 or greater within 4 weeks of first
             dose of study drug

          -  Serious non-healing wound, ulcer or bone fracture

          -  Evidence or history of bleeding diathesis or coagulopathy

          -  Major surgery, open biopsy or significant traumatic injury within 4 weeks of first
             study drug

          -  Any condition that impairs patient's ability to swallow whole pills

          -  Any malabsorption problem

          -  Known hypersensitivity to boron or mannitol

          -  Grade 2 or greater peripheral neuropathy within 14 days before enrollment