ONC-MANILA12: Maintenance Low Dose Oral Navelbine In Patients With Non Small Cell Lung Cancer - MA.NI.LA Trial

Sponsor
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano (Other)
Overall Status
Completed
CT.gov ID
NCT02176369
Collaborator
Regione Lombardia (Other)
120
20
2
68.8
6
0.1

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

Systemic therapy remains the mainstay of treatment of advanced stage NSCLC. Combination chemotherapy with a platinum-based regimen has emerged as standard therapy for patients with advanced stage disease. Observations supported by the findings of several clinical trial, established the notion that an efficacy plateau had been reached in advanced stage NSCLC patients treated with platinum-containing drugs.

Recent phase III trials suggest the benefit of "switch" and "continuing" maintenance treatment with different drugs. As "switched therapy", Vinorelbine has been selected on the base of its anti-mitotic role. In fact, the use of anti-mitotic drugs at lower dose but with higher frequency (metronomic schedule) seems to augment the anti-angiogenetic effect of this kind of drugs, thus augmenting the efficacy of the therapy.

Therefore, the purpose of the current study is to evaluate the role of a "switched maintenance" with oral vinorelbine administered as a metronomic schedule in terms of Progression Free Survival (PFS) in advanced NSCLC patients with stable disease after first line platinum based chemotherapy.

Study Design

Study Type:
Interventional
Actual Enrollment :
120 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Maintenance Metronomic Per OS Navelbine In Advanced NSCLC Patients After Previous Platinum Based Chemotherapy: A Multicenter Randomized Best Supportive Care Controlled Phase II Study - MA.NI.LA. Trial
Actual Study Start Date :
Feb 1, 2013
Actual Primary Completion Date :
Oct 27, 2018
Actual Study Completion Date :
Oct 27, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: vinorelbine

50 mg three times a week for a three weeks cycle

Drug: Vinorelbine
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.
Other Names:
  • Navelbine
  • No Intervention: Close observation/Best Supportive Care

    Close observation/Best Supportive Care (BSC)

    Outcome Measures

    Primary Outcome Measures

    1. Progression Free Survival (PFS) [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)]

      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.

    Secondary Outcome Measures

    1. 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]

      OS: defined as the time from the date of randomization to the date of death from any cause or the last date the patient was known to be alive.

    2. 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]

      ORR, CR+PR: defined as the proportion of patients with measurable disease at baseline achieving partial or complete overall best response according to RECIST version 1.1 criteria.

    3. 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 Response (only in patients in CR or PR): defined as the time from the date of the first documentation of confirmed objective tumor response to the date of first documentation of objective tumor progression, objective tumor recurrence, or of death due to progressive disease, whichever comes first.

    4. 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]

      Duration of Post Progression Survival: defined as the time from the date of first documentation of objective tumor progression to the date of death from any cause or the last date the patient was known to be alive.

    5. 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]

    6. Overall Safety Profile [Assessed at every cycle (3wks) and 28d after last dose intake up to 18 months after LPI]

      Overall Safety Profile, characterized by type, frequency, severity [graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0], timing and relationship to study therapy of adverse events and laboratory abnormalities.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    1. Signed and dated approved ICF

    2. Histologically or cytologically confirmed diagnosis NSCLC diagnosis

    3. 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

    4. 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.

    5. Patients who may have received adjuvant treatment (containing also vinorelbine) at least 6 mos before study entry

    6. ECOG performance status 0-2

    7. 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

    8. Prothrombin time (PT) or INR or aPTT ≤ 1.5 x ULN

    9. Calculated creatinine clearance ≥ 30 mL/min (Cockcroft and Gault Formula)

    10. AST (SGOT) and ALT (SGPT) < 2.5 x ULN, AST and ALT < 5 x ULN (if documented liver metastases)

    11. Serum bilirubin < 2.0 mg/dL (patients with Gilbert's syndrome: serum bilirubin ≤ 3 x ULN

    12. Alkaline phosphatase < 2.5 x ULN (patients with documented liver or bone metastases, alkaline phosphatase ≤ 5 x ULN)

    13. No other obvious related major organ toxicities which would compromise the patient's ability to participate in a clinical trial

    14. 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

    15. 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

    16. Males must agree to use effective birth control for themselves or their partner during the trial and for 12 wks after the last treatment dose

    17. Life expectancy of at least 12 wks

    18. Male or female, age ≥18

    Exclusion Criteria:
    1. Patients who have received induction therapy with platinum obtaining progressive disease

    2. 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)

    3. Patients who have received, or are scheduled to receive, single agent or combination therapy consisting of chemotherapy, targeted, biological, investigational, hormonal as maintenance treatment

    4. Previous treatment for metastatic disease with chemotherapy containing oral or i.v. vinorelbine formulation

    5. Last dose of induction chemotherapy < 21 d prior to randomization or > 42 d prior to randomization

    6. Concurrent treatment with other experimental drugs.

    7. 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)

    8. Major surgery within 4 wks prior to first study drug administration

    9. Active central nervous system (CNS) metastatic disease. Patients with stable CNS disease following completion of radiation therapy and/or surgery are eligible

    10. Active or chronically recurrent bleeding (e.g., active peptic ulcer disease)

    11. Malabsorption syndrome or any other disorder affecting gastrointestinal absorption

    12. Clinically significant infection

    13. 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

    14. 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

    15. 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Ospedale di Gesù Fatebenefratelli Benevento BN Italy 82100
    2 ASL Brindisi - Stabilimento Ospedaliero Di Summa-Perrino Brindisi BR Italy 72100
    3 ASP di Bolzano - Comprensorio sanitario di Bolzano Bolzano BZ Italy 39100
    4 Ospedale Civile SS. Annunziata Chieti CH Italy 66100
    5 A. Ospedaliero-Universitaria Policlinico Vittorio Enmanuele Catania CT Italy 95123
    6 A.O. Villa Scassi Genova GE Italy 16149
    7 Fondazione IRCCS Istituto Nazionale dei Tumori Milano MI Italy 20133
    8 A.O. Ospedale di Circolo di Melegnano - P.O. Vizzolo Predabissi Vizzolo Predabissi MI Italy 20070
    9 A.O. V. Cervello Palermo PA Italy 90146
    10 Casa di Cura La Maddalena Palermo PA Italy 90146
    11 AUSL Piacenza - Ospedale Guglielmo da Saliceto Piacenza PC Italy 29121
    12 A.O. Santa Maria Degli Angeli Pordenone PN Italy 33170
    13 Azienda USL 4 Prato - O.C. Misericordia e Dolce Prato PO Italy 59100
    14 Azienda Ulss18 - Ospedale S.M. della Misericordia Rovigo RO Italy 45100
    15 Ospedale Morelli Sondalo SO Italy 23100
    16 A.O. Valtellina e Valchiavenna - Ospedale di Sondrio Sondrio SO Italy 23100
    17 A.O. Ospedale di Circolo di Busto Arsizio Busto Arsizio VA Italy 21052
    18 Ospedale di Circolo e Fondazione Macchi Varese VA Italy 21100
    19 Casa di Cura Dott. Pederzoli Peschiera del Garda VR Italy 37019
    20 AUSL Viterbo - Ospedale di Belcolle Viterbo VT Italy 01100

    Sponsors and Collaborators

    • Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
    • Regione Lombardia

    Investigators

    • Principal Investigator: 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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
    ClinicalTrials.gov Identifier:
    NCT02176369
    Other Study ID Numbers:
    • ONC-MANILA12
    • 2012-001103-21
    First Posted:
    Jun 27, 2014
    Last Update Posted:
    Apr 22, 2019
    Last Verified:
    Apr 1, 2019
    Keywords provided by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Apr 22, 2019