Brief Title
Metronomic Chemotherapy Based on Adaptative Bio-mathematical Model of Oral Vinorelbine in Patients With NSCLC or MPM
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
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.
Study Phase
Phase 1
Study Type
Interventional
Primary Outcome
Phase IA : Treatment-related hematological toxicities (neutropenia) of grade 3-4 as assessed by CTCAE v4.0
Condition
Non Small Cell Lung Cancer (NSCLC)
Intervention
Vinorelbine
Study Arms / Comparison Groups
Oral Vinorelbine
Description:
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
32
Start Date
August 2015
Primary Completion Date
August 2018
Eligibility Criteria
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
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Urielle DESALBRES, Director, +33491384644, [email protected]
Location Countries
France
Location Countries
France
Administrative Informations
NCT ID
NCT02555007
Organization ID
2014-53
Responsible Party
Sponsor
Study Sponsor
Assistance Publique Hopitaux De Marseille
Study Sponsor
Urielle DESALBRES, Director, Study Director, Assistance Publique des Hôpitaux de Marseille
Verification Date
September 2015