Study of Patient Preference for Oral or Intravenous Vinorelbine in the Treatment of Advanced NSCLC (VIVOS)

Randomized Cross-over Study of Patient Preference for Oral or Intravenous Vinorelbine in the Treatment of Advanced NSCLC. A Phase IV Study.

Title: Randomized cross-over study of patient preference for oral or intravenous vinorelbine in the treatment of advanced NSCLC. A phase IV study.

ShortTitle/ Acronym: VIVOS

Protocol Code :IRST162.05

Study Design: Randomized, open label cross-over study

Study Duration: Two years

Study Center(s): Multicenter study

Objectives:

Primary: Patient preference for oral or intravenous vinorelbine Secondary: Overall Response Rate, Time to Progression, Toxicity, Survival, Subjective reasons for treatment choice.

Number of Subjects: 120

Diagnosis and Main Inclusion Criteria:

Patients affected by stage IIIB or stage IV NSCLC candidates to receive a first line chemotherapy with vinorelbine due to age ≥ 70 and Eastern Cooperative Oncology Group (ECOG) Performance status ≤2 or age ≤ 70 but ECOG PS ≥ 2

Study Product, Dose, Route, Regimen and duration of administration :

• Arm A: first cycle of IV vinorelbine (30 mg/m2) and second cycle of PO vinorelbine (60mg/m2)
• Arm B: first cycle with PO vinorelbine (60mg/m2) followed by a second cycle of IV vinorelbine (30mg/m2) In both arms vinorelbine will be given at day 1 and day 8 every 3 weeks. From the third cycle onwards patients will have to choose to receive oral or intravenous vinorelbine. Vinorelbine capsules will be administered at the dosage of 60 mg/m2 for the first course and then may be increased to 80 mg/m² at physician's choice.

Treatment will be repeated every 21 days and continued until disease progression, intolerable toxicity or patient refusal.

Reference therapy: Vinorelbine 30 mg/m2 intravenous day 1 and 8 every 21 days

Statistical Methodology: The sample size is calculated based on 75% of patients preferring "oral" vinorelbine and 25% preferring "intravenous" vinorelbine. Therefore, the investigators would compare patients preferring "oral" vinorelbine as 75% compared to a null hypothesis of 50% (no difference in proportion of patients preferring "oral" to "intravenous"). With 80% power and a total alpha of 0.05, the estimated sample size is 60 for group (120 total). During recruitment period, a formal interim analysis was planned when 60 patients (30 for group) have been enrolled, with a p-value <0.0001. To claim statistical significance in the final analysis, the overall p-value is still 5% (referred to Peto-Haybittle rule).

Study Overview

• Status: Completed
• Conditions: Non-small Cell Lung Cancer Metastatic
• Intervention / Treatment: Drug: Vinorelbine

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Phase 4

Contacts and Locations

Study Locations

• Italy
  • Belluno, Italy, 32100
    • U.O. Oncologia Medica ULSS 1 Belluno
  • Rimini, Italy
    • U.O. Oncologia Ospedale degli Infermi
  • FC
    • Meldola (FC), FC, Italy, 47014
      • Irccs Irst
  • RA
    • Faenza, RA, Italy, 48018
      • U.O. Oncologia Ospedale Civile degli Infermi
    • Lugo, RA, Italy, 48022
      • U.O. Oncologia Ospedale Civile Umberto I
    • Ravenna, RA, Italy, 48121
      • UO Oncologia Medica, Ospedale S.Maria delle Croci
  • RN
    • Cattolica, RN, Italy, 47841
      • U.O. Oncologia Ospedale Cervesi
  • VE
    • Mirano, VE, Italy, 30035
      • U.O. Oncologia ed Ematologia Oncologica ULSS 13 MIRANO

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Histologically or cytologically confirmed stage IIIB or IV NSCLC.
2. Age ≥ 70 and Eastern Cooperative Oncology Group (ECOG) Performance status ≤2 or age ≤ 70 but ECOG PS ≥ 2
3. Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >20 mm with conventional techniques or as >10 mm with spiral CT scan. See section 9.2 and Appendix E for the evaluation of measurable disease.
4. Patients with asymptomatic brain metastases are eligible
5. Patients with recurrent disease after previous surgery are eligible
6. Life expectancy > 3 months
7. Patients must have normal organ and marrow function
8. Female participants of child bearing potential and male participants whose partner is of child bearing potential must be willing to ensure that they or their partner use effective contraception during the study and for 3 months thereafter
9. Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

The participant may not enter the study if ANY of the following apply:

1. Patients who have had previous chemotherapy for lung cancer or radiotherapy on target lesions.
2. Participation in another clinical trial with any investigational agents within 30 days prior to study screening.
3. Presence of infection.
4. Preexisting clinically significant peripheral neuropathy.
5. History or evidence of malabsorption syndrome or disease that may significantly affect gastrointestinal function.
6. Patients with known symptomatic uncontrolled brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
7. History of allergic reactions attributed to compounds of similar chemical or biologic composition to vinorelbine or other agents used in the study.
8. Presence of medical problems of sufficient severity to prevent full compliance with the study.
9. Other known malignant neoplastic diseases in the patient's medical history with a disease-free interval of less than 5 years (except for previously treated basal cell carcinoma and in situ carcinoma of the uterine cervix);

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A; •Arm A: first cycle of IV vinorelbine (30 mg/m2) and second cycle of PO vinorelbine (60mg/m2)	Drug: Vinorelbine
Experimental: Arm B; • Arm B: first cycle with PO vinorelbine (60mg/m2) followed by a second cycle of IV vinorelbine (30mg/m2)	Drug: Vinorelbine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patients preference for IV or PO vinorelbine.	At the time of patient preference, a questionnaire will be filled in by patients.	2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall survival (OS)	2 years
Progression-free survival (PFS)	2 years
Overall response rate (RR)	2 years
Toxicity of both drug formulations	2 years
Subjective reasons for treatment choice	2 years

Collaborators and Investigators

• Sponsor: Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
• Investigators: Study Chair: Claudio Dazzi, MD, UO Oncologia Medica, Ospedale S.Maria delle Croci, RAVENNA - ITALY

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2012
• Primary Completion (Actual): October 1, 2016
• Study Completion (Actual): May 1, 2018

Study Registration Dates

• First Submitted: April 26, 2013
• First Submitted That Met QC Criteria: May 6, 2013
• First Posted (Estimate): May 7, 2013

Study Record Updates

• Last Update Posted (Actual): November 9, 2018
• Last Update Submitted That Met QC Criteria: November 8, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Vinorelbine
• Other Study ID Numbers: IRST162.05; 2012-003544-68 (EudraCT Number)