Metronomic Oral Vinorelbine in Patients With Metastatic Tumors

• progression free survival [ Time Frame: Patients will be assessed every 2 months during the first 6 months on treatment and every 4 months thereafter until documentation of objective tumor progression or death. ] [ Designated as safety issue: No ]
• time to progression [ Time Frame: Patients will be assessed every 2 months during the first 6 months on treatment and every 4 months thereafter until documentation of objective tumor progression. ] [ Designated as safety issue: No ]
• toxicity [ Time Frame: Acute toxicity will be assessed during the first 8 weeks, sub-acute 8 weeks to 4 months, chronic post 4 months ] [ Designated as safety issue: Yes ]
• changes in blood concentrations of angiogenesis-associated surrogate markers and pharmacokinetics [ Time Frame: Baseline values will be assessed for predictive potential and assessment on weeks 2,4,8, 12 and thereafter every 2 months they will be analyzed for their capacity to act as surrogate markers of treatment activity ] [ Designated as safety issue: No ]

Patients with recurrent or metastatic solid tumors receive oral vinorelbine at one of three different doses (30 or 40 or 50 mg). Vinorelbine will be administered orally at a metronomic schedule three times a week: on Monday, Wednesday and Friday.

The purpose of this study is to define the biologically optimal dose of vinorelbine when administered at a metronomic dosing schema. [Metronomic chemotherapy refers to the close, regular administration of minimally toxic doses of cytotoxic drugs, with minimal or no drug-free breaks, over prolonged periods]. Patients with recurrent or metastatic solid tumors are randomly assigned one of three different doses of oral vinorelbine (30 or 40 or 50 mg). Treatment is administered three times a week (Monday, Wednesday and Friday) continuously until disease progression or unacceptable toxicity or to a maximum of 24 months.

• Breast Cancer
• Non Small Cell Lung Cancer
• Prostate Cancer

• Active Comparator: 1
  Intervention: Drug: vinorelbine oral formulation
• Active Comparator: 2
  Intervention: Drug: vinorelbine oral formulation
• Active Comparator: 3
  Intervention: Drug: vinorelbine oral formulation

Inclusion Criteria:

• Signed informed consent
• Ages 16 - 75 years
• Genders: both
• Performance status 0-2 according to the World Health Organization (WHO) scale
• Life expectancy of at least 16 weeks
• Adequate bone marrow, hepatic and renal functions
• Absence of brain metastasis
• Metastatic/locally advanced refractory prostate, breast or non-small cell lung cancer previously treated with no more than two chemotherapeutic regimens
• White blood cells >= 3500/mm^3
• Absolute neutrophil count >= 1500/mm^3
• Platelets >= 100,000/mm^3
• Total serum bilirubin less than 1.5 mg/dl
• Serum transaminases less than 2.0 x upper normal limit (UNL) unless attributed to liver metastases
• Serum creatinine within normal range

Exclusion Criteria:

• Major active infection
• More than two prior chemotherapy regimens for metastatic disease

• Any of the following within the 12 months prior to starting the study treatment:

  • myocardial infarction,
  • severe/unstable angina,
  • coronary/peripheral artery bypass graft,
  • congestive heart failure,
  • cerebrovascular accident or transient ischemic attack, or pulmonary embolism,
  • cardiac dysrhythmias of grade >/= 2,
  • atrial fibrillation of any grade, or
  • heart rate corrected interval (QTc) > 450 msec for males or > 470 msec for females.
• Hypertension that cannot be controlled with medications (> 150/100 mmHg despite optimal medical therapy)
• Ongoing anti-coagulation therapy
• Pregnancy or breastfeeding
• Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that would impart, in the judgment of the investigator, excess risk associated with study participation or study drug administration; or which, in the judgment of the investigator, would make the patient inappropriate for entry into the trial.