Neurotoxicity Characterization Study of Nab-paclitaxel Versus Conventional Paclitaxel in Metastatic Breast Cancer

Summary

Nanomedicines are currently being developed in the treatment of cancer due to their pharmacological advantages over traditional formulations; they provide a shorter infusion time and lower risks of hypersensitivity reactions associated with commonly used solvents.

Nab-paclitaxel is a nanoparticle albumin-bound particle form of paclitaxel that is thought to exploit natural albumin pathways to enhance the selective uptake and accumulation of paclitaxel at the site of the tumour, thus reducing its diffusion to normal tissues.

Nab-paclitaxel has been approved for the treatment of metastatic breast cancer patients who have failed first-line treatment for metastatic disease and for whom standard, anthracycline-containing therapy is not indicated.

SPARC is a cysteine rich acid protein that is overexpressed in a broad proportion of solid tumours. Expression of this protein could sensitize tumour cells to antitumor activity of Nab-paclitaxel, due to its union through albumin-binding to this protein.

First-line clinical trials have been developed with different Nab-paclitaxel regimens and also in combination with different chemotherapies and trastuzumab, showing a high level of efficacy.

Toxicity profile of Nab-paclitaxel is well characterized with significantly less haematological toxicities compared with conventional paclitaxel.

Nab-paclitaxel derived grade III neuropathy is short-lasting and more reversible than conventional paclitaxel-derived neuropathy, probably due to absence of Cremophor solvent, or due to paclitaxel itself.

However there is still a lack of clinical and physiological characterisation of Nab-paclitaxel induced neuropathy.

The current used tools for early detection and continuous evaluation of neurotoxicity are not optimal. Most used toxicity scales are limited, as they do not provide a detailed information of the severity of the neuropathy, its impact on quality of life, or physiopathology mechanisms.

In addition, an inter-individual variability exists in terms of neurotoxicity predisposition when taxanes are used; it could be related to polymorphic differences in genes implicated in transport and metabolism of these drugs.

Conditions

• Breast Cancer

Interventions

DRUG

Paclitaxel 80 mg/m2

Paclitaxel 80 mg/m2 days 1, 8 and 15

DRUG

Nab-paclitaxel 100 mg/m2 days 1, 8 and 15

Nab-paclitaxel 100 mg/m2 days 1, 8 and 15

DRUG

Nab-paclitaxel 150 mg/m2 days 1, 8 and 15

Nab-paclitaxel 150 mg/m2 days 1, 8 and 15

DRUG

Nab-paclitaxel 150 mg/m2 days 1 and 15

Nab-paclitaxel 150 mg/m2 days 1 and 15

Sponsors & Collaborators

• Fundacion Oncosur

  lead NETWORK

Principal Investigators

• Eva Ciruelos, MD · Hospital 12 de Octubre, Servicio de Oncología Médica

• Noelia Martínez, MD · Hoapital Ramón y Cajal, Servicio de Oncología Médica

• Rafael Carrión, MD · Hospital Universitario del Sureste, Servicio de Oncología Médica

• José A García Sáenz, MD · Hospital Clínico San Carlos, Servicio de Oncología Médica

• María Echarri, Md · Hospital Universitario Severo Ochoa, Servicio de Oncología Médica

• Blanca Cantos, MD · Hospital Universitario Puerta de hierro Majadahonda, Servicio de Oncología Médica

• Coralía Bueno, MD · Hospital Universitario Infanta Cristina, Servicio de Oncología Médica

• Miguel A Lara, MD · Hospital Universitario Infanta Leonor

• Santos Enrech, MD · Hospital Universitario de Getafe, Servicio de Oncología Médica

• Juan A Guerra, MD · Hospital Universitario de Fuenlabrada

Study Design

Allocation

RANDOMIZED

Purpose

DIAGNOSTIC

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

FEMALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2012-12-31

Primary Completion

2015-12-31

Completion

2015-12-31

Countries

• Spain

Study Locations