Metronomic Chemotherapy Based on Adaptative Bio-mathematical Model of Oral Vinorelbine in Patients With NSCLC or MPM

Sponsor
Assistance Publique Hopitaux De Marseille
Study ID
NCT02555007
Phase
PHASE1
Status
Completed

Conditions

  • Malignant Pleural Mesothelioma (MPM)
  • Non Small Cell Lung Cancer (NSCLC)

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

Study Details

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.

Key Dates

Start date
Aug 26, 2015
Status verified
Nov 2022
Primary completion
Jul 26, 2018
Completion
Oct 25, 2022

Study Design

Enrollment
30 participants (actual)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: Oral Vinorelbine

Primary Outcome Measure

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. ]

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