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

NCT02555007 | Completed Phase 1

• 1 other identifier: 2014-53
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• 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.

• 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.

Study Arms (1)

Oral Vinorelbine

EXPERIMENTAL

Drug: Vinorelbine

Interventions

Vinorelbine DRUG

Oral Vinorelbine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Assistance Publique Hopitaux De Marseille: lead

Study Sites (1)

Assistance Publique des Hôpitaux de Marseille (CEPCM)

Marseille, 13005, France

Location

Related Publications (1)

• Barlesi F, Imbs DC, Tomasini P, Greillier L, Galloux M, Testot-Ferry A, Garcia M, Elharrar X, Pelletier A, Andre N, Mascaux C, Lacarelle B, Cheikh RE, Serre R, Ciccolini J, Barbolosi D. Mathematical modeling for Phase I cancer trials: A study of metronomic vinorelbine for advanced non-small cell lung cancer (NSCLC) and mesothelioma patients. Oncotarget. 2017 Jul 18;8(29):47161-47166. doi: 10.18632/oncotarget.17562.

  PMID: 28525370 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Mesothelioma, Malignant

Interventions

Vinorelbine

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Mesothelioma; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Mesothelial; Pleural Neoplasms

Intervention Hierarchy (Ancestors)

Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines

Study Officials

• Urielle DESALBRES, Director

  Assistance Publique des Hôpitaux de Marseille

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 11, 2015
• First Posted: September 21, 2015
• Study Start: August 26, 2015
• Primary Completion: July 26, 2018
• Study Completion: October 25, 2022
• Last Updated: November 17, 2022

Record last verified: 2022-11

Locations

FR (1)