A Phase II Trial OF Carboplatin, ABI-007 (Abraxane) And Sorafenib (BAY 43-9006) in Metastatic Melanoma
- Histologically confirmed diagnosis of melanoma with measurable disease
- Patients with stage IV, previously untreated, refractory to initial therapy or
progressing after response to initial therapy
- Patients with unresectable stage III, including unresectable in-transit metastases
- Two prior chemotherapy regimen is allowed
- One prior immunotherapy regimen is allowed
- No other concurrent investigational therapy
- Radiation therapy to non-target lesions or to one of multiple target lesions may be
allowed on a case-by-case basis
- Patients must be past the nadir from previous cytotoxic therapy
- Age at least 18 years
- ECOG performance status 0-2
- Hemoglobin > 9.0 g/dl, absolute neutrophil count (ANC) > 1,500/mm3, platelet count >
- Total bilirubin within normal limits, ALT and AST < 2.0 x the ULN ( < 5 x ULN for
patients with liver involvement), INR < 1.5 and aPTT within normal limits. Patients
who receive anti-coagulation treatment with an agent such as warfarin or heparin may
be allowed to participate. For patients on warfarin, close monitoring of at least
weekly evaluations will be performed until INR is stable based on a measurement at
pre dose, as defined by the local standard of care.
- Creatinine < 1.5 x ULN, serum calcium within normal limits
- Patients with stable brain metastasis who have been treated with either whole brain
radiation or Gamma Knife and have been off steroids for > 4 weeks
- 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 and women should use adequate birth control for at least three
months after the last administration of protocol drugs. Women of childbearing
potential must have a negative serum pregnancy test performed within 7 days prior to
the start of treatment.
- Ability to understand and sign a written informed consent document. All patients must
have a signed informed consent before registration and initiation of therapy
- Cardiac disease: Congestive heart failure > class II NYHA.
- Patients must not have unstable angina (anginal symptoms at rest) or 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.
- No known severe hypersensitivity or suspected allergy to sorafenib, ABI-007 or any of
- Patients with neurological symptoms must undergo a CT scan/MRI of the brain to
exclude progressing brain metastasis.
- Peripheral neuropathy greater than grade II
- Serious intercurrent medical or psychiatric illness, including serious active
- Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C.
- Thrombotic 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
- Any other hemorrhage/bleeding event > CTCAE Grade 3 within 4 weeks of first dose of
- 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
- Use of St. John's Wort or rifampin (rifampicin)
- Any condition that impairs patient's ability to swallow whole pills.
- Any malabsorption problem
- No treatment for melanoma within the previous 4 weeks.