Clinical trial NCT00278070: Metronomic Oral Vinorelbine in Patients With Metastatic Tumors
Official title: Metronomic Vinorelbine in Patients With Metastatic Tumors: Phase II Translational Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Non Small Cell Lung Cancer
Prostate Cancer
Keywords: Metronomic-therapy
vinorelbine
Recurrent Breast Cancer
Recurrent Non Small Cell Lung Cancer
Metastatic prostate cancer
Lead sponsor: Hellenic Cooperative Oncology Group
Sponsor class: OTHER
Collaborators: name: University of Ioannina
First posted: 2006-01-18
Sex: ALL
Minimum age (years): 16
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: time to treatment failure
timeFrame: TTF rates per arm will be compared at 4 and 6 months
Secondary outcomes:
measure: progression free survival
timeFrame: 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.
measure: time to progression
timeFrame: 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.
measure: toxicity
timeFrame: Acute toxicity will be assessed during the first 8 weeks, sub-acute 8 weeks to 4 months, chronic post 4 months
measure: changes in blood concentrations of angiogenesis-associated surrogate markers and pharmacokinetics
timeFrame: 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
Other outcomes:
Locations:
city: Athens
country: Greece
facility: Henry Dunant Hospital
city: Athens
country: Greece
facility: Sotiria Hospital
city: Athens
country: Greece
facility: University Hospital "Attikon"
city: Athens
country: Greece
facility: Agii Anargiri Cancer Hospital
city: Athens
country: Greece
facility: Hygeia Hospital
city: Athens
country: Greece
facility: Metropolitan Hospital
city: Chania
country: Greece
facility: General Hospital of Chania
city: Ioannina
country: Greece
facility: University General Hospital of Ioannina, Medical Oncology Dept
city: Patras
country: Greece
facility: University Hospital of Patras
city: Thessaloniki
country: Greece
facility: "Theagenio" Hospital
city: Thessaloniki
country: Greece
facility: "Papageorgiou" Cancer Hospital
Study officials:
affiliation: Assistant Professor of Oncology, Medical School, University of Ioannina
name: Evangelos Briasoulis, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Briasoulis E, Aravantinos G, Kouvatseas G, Pappas P, Biziota E, Sainis I, Makatsoris T, Varthalitis I, Xanthakis I, Vassias A, Klouvas G, Boukovinas I, Fountzilas G, Syrigos KN, Kalofonos H, Samantas E. Dose selection trial of metronomic oral vinorelbine monotherapy in patients with metastatic cancer: a hellenic cooperative oncology group clinical translational study. BMC Cancer. 2013 May 29;13:263. doi: 10.1186/1471-2407-13-263.