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

Non Small Cell Lung Cancer (NSCLC) Clinical Trial

— NVB Metro  

Official title:

Phase IA/IB of Metronomic Chemotherapy Based on Adaptative Bio-mathematical Model of Oral Vinorelbine in Patients With Non Small Cell Lung Cancer or Malignant Pleural Mesothelioma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02555007
• Other study ID #: 2014-53
• Status: Completed
• Phase: Phase 1
• Start date: August 26, 2015
• Est. completion date: October 25, 2022

Study information

• Verified date: November 2022
• Source: Assistance Publique Hopitaux De Marseille
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: October 25, 2022
• Est. primary completion date: July 26, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Malignant Pleural Mesothelioma (MPM)
• Mesothelioma
• Mesothelioma, Malignant
• Non Small Cell Lung Cancer (NSCLC)

Intervention

Drug:
• Vinorelbine

Locations

Country	Name	City	State
France	Assistance Publique des Hôpitaux de Marseille (CEPCM)	Marseille

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique Hopitaux De Marseille

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase IA : Treatment-related hematological toxicities (neutropenia) of grade 3-4 as assessed by CTCAE v4.0		Participants will be followed for the a maximum period of 24 months.
Primary	Phase IB : Objective response rate according to RECIST1.1 for NSCLC and RECIST1.1 modified for MPM		Participants will be followed for the a maximum period of 24 months.