Metronomic Oral Vinorelbine in Patients With Metastatic Tumors

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Metronomic Vinorelbine in Patients With Metastatic Tumors: Phase II Translational Study

Conditions
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Breast Cancer, Non Small Cell Lung Cancer, Prostate Cancer

Intervention / Treatment
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* Drug: vinorelbine oral formulation


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br> | Drug: vinorelbine oral formulation<br>* Patients will take three times a week [Monday, Wednesday and Friday] by mouth, a standard dose of soft capsules of vinorelbine given at dose ascribed by randomization procedure<br>* Other names: Navelbine;|
| Active Comparator: 2<br> | Drug: vinorelbine oral formulation<br>* Patients will take three times a week [Monday, Wednesday and Friday] by mouth, a standard dose of soft capsules of vinorelbine given at dose ascribed by randomization procedure<br>* Other names: Navelbine;|
| Active Comparator: 3<br> | Drug: vinorelbine oral formulation<br>* Patients will take three times a week [Monday, Wednesday and Friday] by mouth, a standard dose of soft capsules of vinorelbine given at dose ascribed by randomization procedure<br>* Other names: Navelbine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| time to treatment failure |  | TTF rates per arm will be compared at 4 and 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progression free survival |  | 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. | 
| time to progression |  | 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. | 
| toxicity |  | Acute toxicity will be assessed during the first 8 weeks, sub-acute 8 weeks to 4 months, chronic post 4 months | 
| changes in blood concentrations of angiogenesis-associated surrogate markers and pharmacokinetics |  | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metronomic-therapy, vinorelbine, Recurrent Breast Cancer, Recurrent Non Small Cell Lung Cancer, Metastatic prostate cancer