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
Overview
- Phase
- Phase 2
- Intervention
- Vinorelbine
- Conditions
- Non-small Cell Lung Cancer Stage IIIB
- Sponsor
- Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
- Enrollment
- 120
- Locations
- 20
- Primary Endpoint
- Progression Free Survival (PFS)
- Status
- Completed
- Last Updated
- 7 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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)
Exclusion Criteria
- •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)
Arms & Interventions
vinorelbine
50 mg three times a week for a three weeks cycle
Intervention: Vinorelbine
Outcomes
Primary Outcomes
Progression Free Survival (PFS)
Time Frame: 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 Outcomes
- 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)
- 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)
- Overall Safety Profile(Assessed at every cycle (3wks) and 28d after last dose intake up to 18 months after LPI)