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

March 28, 2016 updated by: Fundacion Oncosur

Neurotoxicity Characterization Phase II Randomized Study of Nab-paclitaxel Versus Conventional Paclitaxel as First-line Therapy of Metastatic HER2-negative Breast Cancer.

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
60

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
      • Madrid, Spain, 28040
        • Hospital Clinico San Carlos
      • Madrid, Spain, 28034
        • Hospital Ramon y Cajal
      • Madrid, Spain
        • Hospital 12 De Octubre
      • Madrid, Spain, 28031
        • Hospital Universitario Infanta Leonor
    • Madrid
      • Arganda del Rey, Madrid, Spain, 28500
        • Hospital Universitario del Sureste
      • Fuenlabrada, Madrid, Spain, 28942
        • Hospital Universitario de Fuenlabrada
      • Getafe, Madrid, Spain, 28905
        • Hospital Universitario de Getafe
      • Leganés, Madrid, Spain, 28911
        • Hospital Universitario Severo Ochoa
      • Majadahonda, Madrid, Spain, 28222
        • Hospital Universitario Puerta de Hierro Majadahonda
      • Parla, Madrid, Spain, 28981
        • Hospital Universitario Infanta Cristina

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
TNS - Total Neuropathy Score
Time Frame: Every 3 months up to 6 months
Every 3 months up to 6 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Evaluate the incidence of neuropathy induced by study treatment (conventional paclitaxel vs nab-paclitaxel)
Time Frame: Every 3 weeks up to 24 weeks
Every 3 weeks up to 24 weeks
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
Every 12 weeks up to 24 weeks
Determine the predictive value of genetic variants (SNPs) for the development of neuropathy
Time Frame: In the two weeks before start treatment
In the two weeks before start treatment
Determine the clinical activity of both treatments (response rate, time to progression)
Time Frame: Every 8-12 weeks up to 24 weeks
Every 8-12 weeks up to 24 weeks
Determine toxicity profile and safety of study treatments (NCI-CTCAE v4.0)
Time Frame: Every 2 weeks up to 24 weeks
Every 2 weeks up to 24 weeks
Determine time to neurotoxicity onset
Time Frame: Every 2 weeks up to 24 weeks
Every 2 weeks up to 24 weeks
Determine time to recovery from neurotoxicity
Time Frame: Every 2 weeks up to 24 weeks
Every 2 weeks up to 24 weeks
Determine time to progression
Time Frame: Every 8-12 weeks up to 24 weeks
Every 8-12 weeks up to 24 weeks
Assess quality of live (EORTC QLQ-C30 and EORTC QLQ-CIPN20)
Time Frame: Every 4 weeks up to 24 weeks
Every 4 weeks up to 24 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Fundacion Oncosur

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Eva Ciruelos, MD, Hospital 12 de Octubre, Servicio de Oncologia Medica
  • 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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 1, 2012

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2015

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2015

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 14, 2012

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 4, 2013

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 9, 2013

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 29, 2016

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 28, 2016

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ONCOSUR-2012-01

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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