Background: Metronomic oral Vinorelbine has efficacy in metastatic NSCLC and malignant Pleural Mesothelioma, but all the studies published thus far were based upon a variety of empirical and possibly suboptimal schedules, with inconsistent results. Mathematical modeling showed by simulation that a new metronomic protocol could lead to a better safety and efficacy profile.
Design: This phase Ia/Ib trial was designed to confirm safety (phase Ia) and evaluate efficacy (phase Ib) of a new metronomic oral vinorelbine schedule. Patient with metastatic NSCLC or malignant Pleural Mesothelioma, after failure of standard treatments, ECOG 0-2 and an adequate organ functions, will be eligible. Our mathematical PK-PD model suggested an alternative weekly D1, D2 and D4 innovative schedule (named Vinorelbine Theoretical Protocol) with a dynamic intake of 60, 30 and 60 mg, respectively. Trial recruitment is two-staged as 12 patients are planned to participate in the phase Ia, to confirm safety and consolidate the calibration of the average parameters of the model. Depending the phase Ia result, and after favorable decision of a consultative committee, the extension phase (phase Ib) will be an efficacy study and will include a number of 20 patients receiving the Optimal Vinorelbine Theoretical Protocol. The primary endpoint is the tolerance (assessed by CTC v4.0) for the phase Ia and the objective response according to RECIST 1.1 for the phase Ib.
An ancillary study on circulating angiogenesis biomarkers will be a subproject of the trial.
Discussion: this ongoing trial is the first to prospectively test a mathematical optimized schedule in metronomic chemotherapy. As such, this trial can be considered as a proof-of-concept study demonstrating the feasibility to run a computational-driven protocol to ensure an optimal efficacy/toxicity balance in patients with cancer.
|First Received Date||September 11, 2015|
|Last Changed Date||September 18, 2015|
|Start Date||August 2015|
|Anticipated Primary Completion Date||August 2018|
|Primary Outcome Measures||
Phase IA : Treatment-related hematological toxicities (neutropenia) of grade 3-4 as assessed by CTCAE v4.0 [Time Frame: Participants will be followed for the a maximum period of 24 months.]
Phase IB : Objective response rate according to RECIST1.1 for NSCLC and RECIST1.1 modified for MPM [Time Frame: Participants will be followed for the a maximum period of 24 months.]
|Study Arms / Comparison Groups||1 / 0|
|Recruitment Status||Unknown status|
|Ages||18 Years - N/A|
|Accepts Healthy Volunteers||No|
Fabrice BARLESI, MD, PhD
- Patients (male or female) ≥ 18 years of age.
- Patients with histologically documented, locally advanced or recurrent (stage IIIB) or metastatic (Stage IV) non-small cell lung Cancer or malignant pleural mesothelioma, for which no standard exits.
- Presence of at least one measurable lesion according to RECIST v.1.1 for NSCLC and modified RECIST 1.1 for MPM
- ECOG performance status ≤2
- ECOG performance status >2
- Patients with significant or uncontrolled cardiovascular disease (eg, congestive heart failure, angor, arrhythmia) within 6 months of starting study treatment
- Any neurological or psychiatric condition interfering with the understanding of study
- Infectious condition uncontrolled
- Any other medical condition that would jeopardize the subject participation
|Sponsor||Assistance Publique Hopitaux De Marseille|
|Verification Date||September 2015|