Metronomic Oral Vinorelbine in Patients With Metastatic Tumors

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

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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer; Prostate Cancer; Non Small Cell Lung Cancer
• Intervention / Treatment: Drug: vinorelbine oral formulation

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.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• Greece
  • Athens, Greece, 18547
    • Metropolitan Hospital
  • Athens, Greece, 11526
    • Sotiria Hospital
  • Athens, Greece, 15123
    • Hygeia Hospital
  • Athens, Greece, 11526
    • Henry Dunant hospital
  • Athens, Greece, 124 62
    • University Hospital "Attikon"
  • Athens, Greece, 13122
    • Agii Anargiri Cancer Hospital
  • Chania, Greece, 73300
    • General Hospital of Chania
  • Ioannina, Greece, 45500
    • University General Hospital of Ioannina, Medical Oncology Dept
  • Patras, Greece, 265 00
    • University Hospital of Patras
  • Thessaloniki, Greece, 54007
    • "Theagenio" Hospital
  • Thessaloniki, Greece, 564 03
    • "Papageorgiou" Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 75 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 2	Drug: vinorelbine oral formulation; 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; Other Names: Navelbine
Active Comparator: 1	Drug: vinorelbine oral formulation; 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; Other Names: Navelbine
Active Comparator: 3	Drug: vinorelbine oral formulation; 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; Other Names: Navelbine

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Hellenic Cooperative Oncology Group
• Collaborators: University of Ioannina
• Investigators: Principal Investigator: Evangelos Briasoulis, MD, Assistant Professor of Oncology, Medical School, University of Ioannina

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: January 1, 2006
• Study Completion (Actual): February 1, 2008

Study Registration Dates

• First Submitted: January 17, 2006
• First Submitted That Met QC Criteria: January 17, 2006
• First Posted (Estimate): January 18, 2006

Study Record Updates

• Last Update Posted (Estimate): February 29, 2008
• Last Update Submitted That Met QC Criteria: February 27, 2008
• Last Verified: February 1, 2008

More Information

Terms related to this study

• Keywords: Metastatic prostate cancer; Recurrent Breast Cancer; vinorelbine; Metronomic-therapy; Recurrent Non Small Cell Lung Cancer
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Neoplasms; Lung Diseases; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Neoplastic Processes; Lung Neoplasms; Prostatic Neoplasms; Carcinoma, Non-Small-Cell Lung; Neoplasm Metastasis; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Vinorelbine
• Other Study ID Numbers: HE 50/05