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

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2013 by Asociación Oncosur
Sponsor:
Information provided by (Responsible Party):
Asociación Oncosur
ClinicalTrials.gov Identifier:
NCT01763710
First received: December 14, 2012
Last updated: January 4, 2013
Last verified: January 2013
  Purpose

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.


Condition Intervention Phase
Breast Cancer
Drug: Paclitaxel 80 mg/m2
Drug: Nab-paclitaxel 100 mg/m2 days 1, 8 and 15
Drug: Nab-paclitaxel 150 mg/m2 days 1, 8 and 15
Drug: Nab-paclitaxel 150 mg/m2 days 1 and 15
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Neurotoxicity Characterization Phase II Randomized Study of Nab-paclitaxel Versus Conventional Paclitaxel as First-line Therapy of Metastatic HER2-negative Breast Cancer.

Resource links provided by NLM:


Further study details as provided by Asociación Oncosur:

Primary Outcome Measures:
  • TNS - Total Neuropathy Score [ Time Frame: Every 3 months up to 6 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Evaluate the incidence of neuropathy induced by study treatment (conventional paclitaxel vs nab-paclitaxel) [ Time Frame: Every 3 weeks up to 24 weeks ] [ Designated as safety issue: Yes ]
  • Evaluate the electromyographic abnormalities and the correlation of these alterations with the assessment of the TNS scale and NCI-CTCAE (Common Toxicity Criteria for Adverse Effects) v4.0 [ Time Frame: Every 12 weeks up to 24 weeks ] [ Designated as safety issue: No ]
  • Determine the predictive value of genetic variants (SNPs) for the development of neuropathy [ Time Frame: In the two weeks before start treatment ] [ Designated as safety issue: No ]
  • Determine the clinical activity of both treatments (response rate, time to progression) [ Time Frame: Every 8-12 weeks up to 24 weeks ] [ Designated as safety issue: No ]
  • Determine toxicity profile and safety of study treatments (NCI-CTCAE v4.0) [ Time Frame: Every 2 weeks up to 24 weeks ] [ Designated as safety issue: Yes ]
  • Determine time to neurotoxicity onset [ Time Frame: Every 2 weeks up to 24 weeks ] [ Designated as safety issue: Yes ]
  • Determine time to recovery from neurotoxicity [ Time Frame: Every 2 weeks up to 24 weeks ] [ Designated as safety issue: Yes ]
  • Determine time to progression [ Time Frame: Every 8-12 weeks up to 24 weeks ] [ Designated as safety issue: No ]
  • Assess quality of live (EORTC QLQ-C30 and EORTC QLQ-CIPN20) [ Time Frame: Every 4 weeks up to 24 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: December 2012
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm A
Paclitaxel 80 mg/m2 days 1, 8 and 15
Drug: Paclitaxel 80 mg/m2
Paclitaxel 80 mg/m2 days 1, 8 and 15
Experimental: Arm B
Nab-paclitaxel 100 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
Experimental: Arm C
Nab-paclitaxel 150 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
Experimental: Arm D
Nab-paclitaxel 150 mg/m2 days 1 and 15
Drug: Nab-paclitaxel 150 mg/m2 days 1 and 15
Nab-paclitaxel 150 mg/m2 days 1 and 15

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Women with histologically or cytologically of stage IV breast cancer.
  2. Non-candidate patient to trastuzumab or lapatinib treatment as not presenting HER2 oncogene amplification.
  3. Metastatic disease not previously treated with chemotherapy. It is allowed pre-treatment hormone with anti-target or bisphosphonates for advanced disease.
  4. Measurable or evaluable disease by RECIST criteria.
  5. Previous sensory neuropathy <= grade 1, according to NCI-CTCAE criteria, due to any reason.
  6. Age> 18 years.
  7. Performance status <2 (ECOG).
  8. At least 12 months after the completion of adjuvant chemotherapy with taxanes to diagnosis of metastatic disease.
  9. Creatinine <= 1.5mg/dL, AST (SGOT), ALT (SGPT) and alkaline phosphatase <= 2.5 x ULN (hepatic metastases absent) in the 14 days prior to study entry.
  10. Hemoglobin> 10g/dl, WBC> 3000/mm3, platelets> 100000/mm3 and bilirubin <1.5 mg / dL in the 14 days prior to study entry.
  11. Women of childbearing potential with negative pregnancy test within 14 days prior to study treatment.
  12. Patients using adequate contraception throughout the entire duration of the study and until 4 weeks after completion of treatment.
  13. At least 4 weeks after radiotherapy or major surgery, with complete recovery.
  14. Life expectancy greater than 12 weeks.
  15. Patients who are able to meet the requirements of the protocol.
  16. Patients able to provide with two plasma samples (each sample 5cc) for analyzing polymorphisms.
  17. Written informed consent.

Exclusion Criteria:

  1. Prior chemotherapy treatment for metastatic disease.
  2. Brain metastases.
  3. Concomitant treatment with hormone therapy or immunotherapy for breast cancer, or during the two weeks prior to inclusion in the study.
  4. Any concomitant medical or psychiatric illness including active infection.
  5. History of any malignancy other than breast cancer in the past 5 years except carcinoma or basal cell skin carcinoma or carcinoma in situ of cervix.
  6. Prior treatment with an investigational drug within the last 2 weeks.
  7. Known hypersensitivity to paclitaxel or Cremophor.
  8. Pregnant or breastfeeding.
  9. Have any acute, subacute or chronic peripheral nerve or spinal cord in grade, at the time of inclusion, greater than or equal to 2 (NCI CTCAE v4.0).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01763710

Contacts
Contact: Eva Ciruelos, MD +34659 228 621 eciruelos@hotmail.com
Contact: Juan L Sanz +34918166804 juanluis.sanz@apices.es

Locations
Spain
Hospital Universitario Del Sureste Not yet recruiting
Arganda del Rey, Madrid, Spain, 28500
Contact: Rafael Carrión, MD    +34 918394253    rafael.carrion@salud.madrid.org   
Principal Investigator: Rafael Carrión, MD         
Hospital Universitario de Fuenlabrada Not yet recruiting
Fuenlabrada, Madrid, Spain, 28942
Contact: Juan A Guerra, MD    +34 916006148    jguerra.hflr@salud.madrid.org   
Principal Investigator: Juan A Guerra, MD         
Hospital Universitario de Getafe Not yet recruiting
Getafe, Madrid, Spain, 28905
Contact: Santos Enrech, MD    +34 629453756    senrech1@gmail.com   
Principal Investigator: Santos Enrech, MD         
Hospital Universitario Severo Ochoa Not yet recruiting
Leganés, Madrid, Spain, 28911
Contact: María Echarri, MD    +34 914818000 ext 8329    mecharrigonzalez@yahoo.es   
Principal Investigator: María Echarri, MD         
Hospital Universitario Puerta de Hierro Majadahonda Not yet recruiting
Majadahonda, Madrid, Spain, 28222
Contact: Blanca Cantos, MD    +34 911917731    bcantos@salud.madrid.org   
Principal Investigator: Blanca Cantos, MD         
Hospital Universitario Infanta Cristina Not yet recruiting
Parla, Madrid, Spain, 28981
Contact: Coralía Bueno, MD    +34 687938291    corabumu@hotmail.com   
Principal Investigator: Coralía Bueno, MD         
Hospital Ramón Y Cajal Not yet recruiting
Madrid, Spain, 28034
Contact: Noelia Martínez, MD    +34 913368263    mjnoelia@hotmail.com   
Principal Investigator: Noelia Martínez, MD         
Hospital Universitario Infanta Leonor Not yet recruiting
Madrid, Spain, 28031
Contact: Mifuel A Lara, MD    +34 605581445    mangel.lara@salud.madrid.org   
Principal Investigator: Miguel A Lara, MD         
Hospital 12 de Octubre Recruiting
Madrid, Spain
Contact: Eva Ciruelos, MD       eciruelos.@hotmail.com   
Contact: Juan M Sepúlveda, MD       jmsepulveda76@gmail.com   
Principal Investigator: Eva Ciruelos, MD         
Sub-Investigator: Juan M Sepúlveda, MD         
Hospital Clínico San Carlos Not yet recruiting
Madrid, Spain, 28040
Contact: José A García Sáenz, MD    +34 913303000 ext 7545    jagsaenz@yahoo.com   
Principal Investigator: José A García Sáenz, MD         
Sponsors and Collaborators
Asociación Oncosur
Investigators
Study Director: Eva Ciruelos, MD Hospital 12 de Octubre, Servicio de Oncología Médica
Principal Investigator: Noelia Martínez, MD Hoapital Ramón y Cajal, Servicio de Oncología Médica
Principal Investigator: Rafael Carrión, MD Hospital Universitario del Sureste, Servicio de Oncología Médica
Principal Investigator: José A García Sáenz, MD Hospital Clínico San Carlos, Servicio de Oncología Médica
Principal Investigator: María Echarri, Md Hospital Universitario Severo Ochoa, Servicio de Oncología Médica
Principal Investigator: Blanca Cantos, MD Hospital Universitario Puerta de hierro Majadahonda, Servicio de Oncología Médica
Principal Investigator: Coralía Bueno, MD Hospital Universitario Infanta Cristina, Servicio de Oncología Médica
Principal Investigator: Miguel A Lara, MD Hospital Universitario Infanta Leonor
Principal Investigator: Santos Enrech, MD Hospital Universitario de Getafe, Servicio de Oncología Médica
Principal Investigator: Juan A Guerra, MD Hospital Universitario de Fuenlabrada
  More Information

No publications provided

Responsible Party: Asociación Oncosur
ClinicalTrials.gov Identifier: NCT01763710     History of Changes
Other Study ID Numbers: ONCOSUR-2012-01
Study First Received: December 14, 2012
Last Updated: January 4, 2013
Health Authority: Spain: Agencia Española de Medicamentos y Productos Sanitarios

Keywords provided by Asociación Oncosur:
Breast cancer
Neurotoxicity

Additional relevant MeSH terms:
Breast Neoplasms
Neurotoxicity Syndromes
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Nervous System Diseases
Poisoning
Chemically-Induced Disorders
Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 18, 2014