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

NCT ID: NCT02176369

Last Updated: 2019-04-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-02-28
• Study Completion Date: 2018-10-27

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.

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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

vinorelbine

50 mg three times a week for a three weeks cycle

Group Type: EXPERIMENTAL

Vinorelbine

Intervention Type: 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.

Close observation/Best Supportive Care

Close observation/Best Supportive Care (BSC)

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

Navelbine

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Regione Lombardia

OTHER

Sponsor Role: collaborator

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Marco Platania, MD

Role: PRINCIPAL_INVESTIGATOR

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Alessandro Bertolini, MD

Role: PRINCIPAL_INVESTIGATOR

A.O. Valtellina e Valchiavenna - Ospedale di Sondrio

Andrea De Monte

Role: PRINCIPAL_INVESTIGATOR

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

Luigi Cavanna, MD

Role: PRINCIPAL_INVESTIGATOR

AUSL Piacenza - Ospedale Guglielmo da Saliceto

Marco Bregni, MD

Role: PRINCIPAL_INVESTIGATOR

A.O. Ospedale di Circolo di Busto Arsizio

Yasmina Modena, MD

Role: PRINCIPAL_INVESTIGATOR

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

Fabrizio Nelli, MD

Role: PRINCIPAL_INVESTIGATOR

AUSL Viterbo - Ospedale di Belcolle

Daniele Pozzessere, MD

Role: PRINCIPAL_INVESTIGATOR

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

Hector Soto Parra, MD

Role: PRINCIPAL_INVESTIGATOR

A. Ospedaliero-Universitaria Policlinico Vittorio Emanuele - Catania

Anna Paola Fraccon, MD

Role: PRINCIPAL_INVESTIGATOR

Casa di Cura Dott. Pederzoli - Peschiera del Garda

Saverio Cinieri, MD

Role: PRINCIPAL_INVESTIGATOR

ASL Brindisi - Stabilimento Ospedaliero Di Summa-Perrino

Alessandro Del Conte, MD

Role: PRINCIPAL_INVESTIGATOR

A.O. Santa Maria Degli Angeli - Pordenone

Vittorio Gebbia, MD

Role: PRINCIPAL_INVESTIGATOR

Casa di Cura La Maddalena - Palermo

Manlio Mencoboni, MD

Role: PRINCIPAL_INVESTIGATOR

A.O. Villa Scassi - Genova

Silvia Vattemi, MD

Role: PRINCIPAL_INVESTIGATOR

ASP di Bolzano - Comprensorio sanitario di Bolzano

Mario Saverio Fumanò, MD

Role: PRINCIPAL_INVESTIGATOR

Ospedale Morelli - Sondalo

Francesco Verderame, MD

Role: PRINCIPAL_INVESTIGATOR

A.O.V. Cervello - Palermo

Luciana Irtelli, MD

Role: PRINCIPAL_INVESTIGATOR

Ospedale Civile SS. Annunziata - Chieti

Graziella Pinotti, MD

Role: PRINCIPAL_INVESTIGATOR

Ospedale di Circolo e Fondazione Macchi, Varese

Antonio Febbraro, MD

Role: PRINCIPAL_INVESTIGATOR

Ospedale Sacro Cuore di Gesù Fatebenefratelli - Benevento

Rosa Rita Silva, MD

Role: PRINCIPAL_INVESTIGATOR

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

Gabriella Farina, MD

Role: PRINCIPAL_INVESTIGATOR

A.O. Fatebenefratelli ed Oftalmico - Milano

Antonio Pazzola, MD

Role: PRINCIPAL_INVESTIGATOR

Ospedale Civile SS. Annunziata - Sassari

Locations

Ospedale di Gesù Fatebenefratelli

Benevento, BN, Italy

ASL Brindisi - Stabilimento Ospedaliero Di Summa-Perrino

Brindisi, BR, Italy

ASP di Bolzano - Comprensorio sanitario di Bolzano

Bolzano, BZ, Italy

Ospedale Civile SS. Annunziata

Chieti, CH, Italy

A. Ospedaliero-Universitaria Policlinico Vittorio Enmanuele

Catania, CT, Italy

A.O. Villa Scassi

Genova, GE, Italy

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, MI, Italy

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

Vizzolo Predabissi, MI, Italy

A.O. V. Cervello

Palermo, PA, Italy

Casa di Cura La Maddalena

Palermo, PA, Italy

AUSL Piacenza - Ospedale Guglielmo da Saliceto

Piacenza, PC, Italy

A.O. Santa Maria Degli Angeli

Pordenone, PN, Italy

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

Prato, PO, Italy

Azienda Ulss18 - Ospedale S.M. della Misericordia

Rovigo, RO, Italy

Ospedale Morelli

Sondalo, SO, Italy

A.O. Valtellina e Valchiavenna - Ospedale di Sondrio

Sondrio, SO, Italy

A.O. Ospedale di Circolo di Busto Arsizio

Busto Arsizio, VA, Italy

Ospedale di Circolo e Fondazione Macchi

Varese, VA, Italy

Casa di Cura Dott. Pederzoli

Peschiera del Garda, VR, Italy

AUSL Viterbo - Ospedale di Belcolle

Viterbo, VT, Italy

Countries

Italy

Other Identifiers

2012-001103-21

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ONC-MANILA12

Identifier Type: -

Identifier Source: org_study_id