Maintenance Low Dose Oral Navelbine In Patients With Non Small Cell Lung Cancer - MA.NI.LA Trial

NCT02176369 | Completed Phase 2 DMC

• 2 other identifiers: ONC-MANILA122012-001103-21
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 20

Brief Summary

Non Small Cell Lung Cancer (NSCLC) represents the first cancer related cause of death worldwide with 1.4 millions of deaths every years. Current standard therapies include platinum-containing drugs but at one year from diagnosis the survival rate is still low (30-40%) . The purpose of this study is to evaluate the role of a platinum-free drug, named Vinorelbine, administered by the so called "metronomic schedule" in order to prolong the progression free survival of patients.

Conditions

Non-small Cell Lung Cancer Stage IIIB; Non-small Cell Lung Cancer Stage IV

Keywords

Non small cell lung cancer (NSCLC); Lung tumor in advanced phase

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  PFS: defined as the time from the date of randomization to the date of first documentation of progression, or of death due to any cause, whichever comes first.

  Assessed at every 2 cycles (6 wks), 28d after last dose intake and, for patients discontinuing vinolbine for reason other than PD, every 6 wks during Follow Up, up to 18 mos after the enrollment of the Last Patient (LPI)

Secondary Outcomes (6)

• Overall Survival (OS)

  Assessed at every cycle (3wks), 28d after last dose intake and, during Follow Up, every 3 mos except for patients discontinuing vinolbine for reason other than PD whose assessment is every 6 wks, up to 18 mos after LPI

• Objective Tumor Response Rate (ORR, CR+PR)

  Assessed at every 2 cycles (6wks), 28d after last dose intake and, during Follow Up, every 3 mos except for patients discontinuing vinolbine for reason other than PD whose assessment is every 6 wks, up to 18 mos after LPI

• Duration of Response (only in patients in CR or PR)

  Assessed every two cycles (6wks), 28d after last dose intake and, during Follow Up, every 3 mos except for patients discontinuing vinolbine for reason other than PD whose assessment is every 6 wks, up to 18 mos after LPI

• Duration of Post Progression Survival

  Assessed at 28d after last dose intake and, during Follow Up, every 3 mos except for patients discontinuing vinolbine for reason other than PD whose assessment is every 6 wks, up to 18 mos after LPI

• Quality of Life (QoL) according to EORTC QLC30, EORTC QOL-LC13

  Assessed at every 2 cycles (6wks), 28d after last dose intake and, for patients discontinuing vinolbine for reason other than PD, every 6 wks during Follow Up, up to 18 mos after LPI

Study Arms (2)

vinorelbine

EXPERIMENTAL

50 mg three times a week for a three weeks cycle

Drug: Vinorelbine

Close observation/Best Supportive Care

NO INTERVENTION

Close observation/Best Supportive Care (BSC)

Interventions

Vinorelbine DRUG

Capsule soft (20/30 mg) - 50 mg three times a week (monday, wednesday and friday) for a three weeks cycle (then recycled the next week at the same doses)Treatment will be continued until progression, unacceptable toxicity or death.

Also known as: Navelbine

vinorelbine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed and dated approved ICF
• Histologically or cytologically confirmed diagnosis NSCLC diagnosis
• Stage IV (using AJCC 7th edition, or wet IIIb / IV using the 6th edition), or recurrent locally advanced disease not amenable to radiation or surgery with curative intent and not amenable to concurrent chemoradiation
• Patients with stable disease, after four-six cycles of platinum-based chemotherapy as first line therapy. Patients with partial or complete response during first line chemotherapy according to RECIST criteria can be enrolled provided that they have stable disease at the study entry.
• Patients who may have received adjuvant treatment (containing also vinorelbine) at least 6 mos before study entry
• ECOG performance status 0-2
• Adequate bone marrow reserve as measured by ANC ≥ 1500/mm3, hemoglobin ≥ 9 g/dL, platelet count ≥ 100,000/μL, ≥ 1 week after last transfusion of blood products and/or last dose of hematopoietic growth factor
• Prothrombin time (PT) or INR or aPTT ≤ 1.5 x ULN
• Calculated creatinine clearance ≥ 30 mL/min (Cockcroft and Gault Formula)
• AST (SGOT) and ALT (SGPT) \< 2.5 x ULN, AST and ALT \< 5 x ULN (if documented liver metastases)
• Serum bilirubin \< 2.0 mg/dL (patients with Gilbert's syndrome: serum bilirubin ≤ 3 x ULN
• Alkaline phosphatase \< 2.5 x ULN (patients with documented liver or bone metastases, alkaline phosphatase ≤ 5 x ULN)
• No other obvious related major organ toxicities which would compromise the patient's ability to participate in a clinical trial
• Allowed prior radiation therapy for local or locally advanced disease providing that any clinically significant adverse effects associated with prior therapy have recovered to Grade 1 or less
• Women of childbearing potential must have a negative serum pregnancy test and agree to use effective birth control during the trial and for 12 wks after the last treatment dose

You may not qualify if:

• Patients who have received induction therapy with platinum obtaining progressive disease
• Patients who can benefit from pemetrexed maintenance treatment (adenocarcinoma and ECOG PS 0-1) should be excluded. Enrollment in the trial is permitted for patients who refuse maintenance with pemetrexed or in case of clinical contraindications to pemetrexed therapy (for example renal failure, creatinine clearance ≤ 45 mL/min)
• Patients who have received, or are scheduled to receive, single agent or combination therapy consisting of chemotherapy, targeted, biological, investigational, hormonal as maintenance treatment
• Previous treatment for metastatic disease with chemotherapy containing oral or i.v. vinorelbine formulation
• Last dose of induction chemotherapy \< 21 d prior to randomization or \> 42 d prior to randomization
• Concurrent treatment with other experimental drugs.
• Radiation therapy within 3 wks prior to randomization (palliative radiation therapy is allowed, provided that sites of bone marrow production, i.e., iliac crests are not in the radiation field)
• Major surgery within 4 wks prior to first study drug administration
• Active central nervous system (CNS) metastatic disease. Patients with stable CNS disease following completion of radiation therapy and/or surgery are eligible
• Active or chronically recurrent bleeding (e.g., active peptic ulcer disease)
• Malabsorption syndrome or any other disorder affecting gastrointestinal absorption
• Clinically significant infection
• Clinically significant cardiovascular disease or condition including: congestive heart failure (CHF) requiring therapy, need for anti-arrhythmic therapy for a ventricular arrhythmia, severe conduction disturbance, angina pectoris requiring therapy, medically uncontrolled hypertension per the Investigator's discretion, myocardial infarction within 6 mos prior to first study drug administration, New York Heart Association Class II, III, or IV cardiovascular disease
• Any other severe, acute, or chronic medical or psychiatric condition, laboratory abnormality, or difficulty complying with protocol requirements that may increase the risk associated with study participation or study drug administration or may interfere with the interpretation of study results and, in the judgment of the Investigator
• History of neoplasm other than curatively treated non-melanoma skin cancer or other carcinoma in situ, that has been resected, unless that prior malignancy was diagnosed and definitely treated at least 3 ys previously with no subsequent evidence of recurrence

Sponsors & Collaborators

• Fondazione IRCCS Istituto Nazionale dei Tumori, Milano: lead
• Regione Lombardia: collaborator

Study Sites (20)

Ospedale di Gesù Fatebenefratelli

Benevento, BN, 82100, Italy

Location

ASL Brindisi - Stabilimento Ospedaliero Di Summa-Perrino

Brindisi, BR, 72100, Italy

Location

ASP di Bolzano - Comprensorio sanitario di Bolzano

Bolzano, BZ, 39100, Italy

Location

Ospedale Civile SS. Annunziata

Chieti, CH, 66100, Italy

Location

A. Ospedaliero-Universitaria Policlinico Vittorio Enmanuele

Catania, CT, 95123, Italy

Location

A.O. Villa Scassi

Genova, GE, 16149, Italy

Location

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, MI, 20133, Italy

Location

A.O. Ospedale di Circolo di Melegnano - P.O. Vizzolo Predabissi

Vizzolo Predabissi, MI, 20070, Italy

Location

A.O. V. Cervello

Palermo, PA, 90146, Italy

Location

Casa di Cura La Maddalena

Palermo, PA, 90146, Italy

Location

AUSL Piacenza - Ospedale Guglielmo da Saliceto

Piacenza, PC, 29121, Italy

Location

A.O. Santa Maria Degli Angeli

Pordenone, PN, 33170, Italy

Location

Azienda USL 4 Prato - O.C. Misericordia e Dolce

Prato, PO, 59100, Italy

Location

Azienda Ulss18 - Ospedale S.M. della Misericordia

Rovigo, RO, 45100, Italy

Location

Ospedale Morelli

Sondalo, SO, 23100, Italy

Location

A.O. Valtellina e Valchiavenna - Ospedale di Sondrio

Sondrio, SO, 23100, Italy

Location

A.O. Ospedale di Circolo di Busto Arsizio

Busto Arsizio, VA, 21052, Italy

Location

Ospedale di Circolo e Fondazione Macchi

Varese, VA, 21100, Italy

Location

Casa di Cura Dott. Pederzoli

Peschiera del Garda, VR, 37019, Italy

Location

AUSL Viterbo - Ospedale di Belcolle

Viterbo, VT, 01100, Italy

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Vinorelbine

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines

Study Officials

• Marco Platania, MD

  Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

  PRINCIPAL INVESTIGATOR

• Alessandro Bertolini, MD

  A.O. Valtellina e Valchiavenna - Ospedale di Sondrio

  PRINCIPAL INVESTIGATOR

• Andrea De Monte

  A.O. Ospedale di Circolo di Melegnano - P.O. Vizzolo Predabissi

  PRINCIPAL INVESTIGATOR

• Luigi Cavanna, MD

  AUSL Piacenza - Ospedale Guglielmo da Saliceto

  PRINCIPAL INVESTIGATOR

• Marco Bregni, MD

  A.O. Ospedale di Circolo di Busto Arsizio

  PRINCIPAL INVESTIGATOR

• Yasmina Modena, MD

  Azienda Ulss18 - Ospedale S.M. della Misericordia - Rovigo

  PRINCIPAL INVESTIGATOR

• Fabrizio Nelli, MD

  AUSL Viterbo - Ospedale di Belcolle

  PRINCIPAL INVESTIGATOR

• Daniele Pozzessere, MD

  Azienda USL 4 Prato - O.C. Misericordia e Dolce

  PRINCIPAL INVESTIGATOR

• Hector Soto Parra, MD

  A. Ospedaliero-Universitaria Policlinico Vittorio Emanuele - Catania

  PRINCIPAL INVESTIGATOR

• Anna Paola Fraccon, MD

  Casa di Cura Dott. Pederzoli - Peschiera del Garda

  PRINCIPAL INVESTIGATOR

• Saverio Cinieri, MD

  ASL Brindisi - Stabilimento Ospedaliero Di Summa-Perrino

  PRINCIPAL INVESTIGATOR

• Alessandro Del Conte, MD

  A.O. Santa Maria Degli Angeli - Pordenone

  PRINCIPAL INVESTIGATOR

• Vittorio Gebbia, MD

  Casa di Cura La Maddalena - Palermo

  PRINCIPAL INVESTIGATOR

• Manlio Mencoboni, MD

  A.O. Villa Scassi - Genova

  PRINCIPAL INVESTIGATOR

• Silvia Vattemi, MD

  ASP di Bolzano - Comprensorio sanitario di Bolzano

  PRINCIPAL INVESTIGATOR

• Mario Saverio Fumanò, MD

  Ospedale Morelli - Sondalo

  PRINCIPAL INVESTIGATOR

• Francesco Verderame, MD

  A.O.V. Cervello - Palermo

  PRINCIPAL INVESTIGATOR

• Luciana Irtelli, MD

  Ospedale Civile SS. Annunziata - Chieti

  PRINCIPAL INVESTIGATOR

• Graziella Pinotti, MD

  Ospedale di Circolo e Fondazione Macchi, Varese

  PRINCIPAL INVESTIGATOR

• Antonio Febbraro, MD

  Ospedale Sacro Cuore di Gesù Fatebenefratelli - Benevento

  PRINCIPAL INVESTIGATOR

• Rosa Rita Silva, MD

  ASUR Marche Area Vasta 2 - Ospedale E. Profili - Fabriano (AN)

  PRINCIPAL INVESTIGATOR

• Gabriella Farina, MD

  A.O. Fatebenefratelli ed Oftalmico - Milano

  PRINCIPAL INVESTIGATOR

• Antonio Pazzola, MD

  Ospedale Civile SS. Annunziata - Sassari

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 11, 2014
• First Posted: June 27, 2014
• Study Start: February 1, 2013
• Primary Completion: October 27, 2018
• Study Completion: October 27, 2018
• Last Updated: April 22, 2019

Record last verified: 2019-04

Locations

IT (20)