Breast CancerPhase 2neurabraxNCT01763710
Neurotoxicity Characterization Study of Nab-paclitaxel Versus Conventional Paclitaxel in Metastatic Breast Cancer
A Phase 2 study testing Paclitaxel 80 mg/m2, Nab-paclitaxel 100 mg/m2 days 1, 8 and 15 and Nab-paclitaxel 150 mg/m2 days 1, 8 and 15 in people with Breast Cancer, run by Fundacion Oncosur at 10 sites in Spain.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Paclitaxel 80 mg/m2, Nab-paclitaxel 100 mg/m2 days 1, 8 and 15 and Nab-paclitaxel 150 mg/m2 days 1, 8 and 15
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 10 sitesSpain
- Study dates
- Dec 2012to Dec 2015
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Women with histologically or cytologically of stage IV breast cancer.
- Non-candidate patient to trastuzumab or lapatinib treatment as not presenting HER2 oncogene amplification.
- Metastatic disease not previously treated with chemotherapy. It is allowed pre-treatment hormone with anti-target or bisphosphonates for advanced disease.
- Measurable or evaluable disease by RECIST criteria.
- Previous sensory neuropathy <= grade 1, according to NCI-CTCAE criteria, due to any reason.
- Age> 18 years.
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- Performance status <2 (ECOG).
- At least 12 months after the completion of adjuvant chemotherapy with taxanes to diagnosis of metastatic disease.
- 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.
- Hemoglobin> 10g/dl, WBC> 3000/mm3, platelets> 100000/mm3 and bilirubin <1.5 mg / dL in the 14 days prior to study entry.
- Women of childbearing potential with negative pregnancy test within 14 days prior to study treatment.
- Patients using adequate contraception throughout the entire duration of the study and until 4 weeks after completion of treatment.
- At least 4 weeks after radiotherapy or major surgery, with complete recovery.
- Life expectancy greater than 12 weeks.
- Patients who are able to meet the requirements of the protocol.
- Patients able to provide with two plasma samples (each sample 5cc) for analyzing polymorphisms.
- Written informed consent.
Who cannot join
- Prior chemotherapy treatment for metastatic disease.
- Brain metastases.
- Concomitant treatment with hormone therapy or immunotherapy for breast cancer, or during the two weeks prior to inclusion in the study.
- Any concomitant medical or psychiatric illness including active infection.
- 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.
- Prior treatment with an investigational drug within the last 2 weeks.
Show all 9Show fewer
- Known hypersensitivity to paclitaxel or Cremophor.
- Pregnant or breastfeeding.
- 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).
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
Spain10 sites
Hospital Universitario Del Sureste
Arganda, Madrid, 28500
Hospital Universitario de Fuenlabrada
Fuenlabrada, Madrid, 28942
Hospital Universitario de Getafe
Getafe, Madrid, 28905
Hospital Universitario Severo Ochoa
Leganés, Madrid, 28911
Hospital Universitario Infanta Leonor
Madrid, Madrid, 28031
Hospital Ramón Y Cajal
Madrid, Madrid, 28034
Hospital Clínico San Carlos
Madrid, Madrid, 28040
Hospital 12 de Octubre
Madrid, Madrid
Hospital Universitario Puerta de Hierro Majadahonda
Majadahonda, Madrid, 28222
Hospital Universitario Infanta Cristina
Parla, Madrid, 28981
About this study
Official title: 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.
Read more
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
- Being tested
- Paclitaxel 80 mg/m2, Nab-paclitaxel 100 mg/m2 days 1, 8 and 15, Nab-paclitaxel 150 mg/m2 days 1, 8 and 15, Nab-paclitaxel 150 mg/m2 days 1 and 15
- Keywords
- Breast cancer, Neurotoxicity
- Medical subject headings
- Breast Neoplasms, Neurotoxicity Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Paclitaxel 80 mg/m2Drug
Paclitaxel 80 mg/m2 days 1, 8 and 15
Nab-paclitaxel 100 mg/m2 days 1, 8 and 15Drug
Nab-paclitaxel 100 mg/m2 days 1, 8 and 15
Nab-paclitaxel 150 mg/m2 days 1, 8 and 15Drug
Nab-paclitaxel 150 mg/m2 days 1, 8 and 15
Nab-paclitaxel 150 mg/m2 days 1 and 15Drug
Nab-paclitaxel 150 mg/m2 days 1 and 15
| Study group | Role | What they receive |
|---|---|---|
| Arm A | Active comparator | Paclitaxel 80 mg/m2 days 1, 8 and 15 Receives: Drug: Paclitaxel 80 mg/m2 |
| Arm B | Experimental | Nab-paclitaxel 100 mg/m2 days 1, 8 and 15 Receives: Drug: Nab-paclitaxel 100 mg/m2 days 1, 8 and 15 |
| Arm C | Experimental | Nab-paclitaxel 150 mg/m2 days 1, 8 and 15 Receives: Drug: Nab-paclitaxel 150 mg/m2 days 1, 8 and 15 |
| Arm D | Experimental | Nab-paclitaxel 150 mg/m2 days 1 and 15 Receives: Drug: Nab-paclitaxel 150 mg/m2 days 1 and 15 |
What is being measured
The primary outcome is the main question the study is designed to answer.
TNS - Total Neuropathy Score
Measured: Every 3 months up to 6 months
Secondary outcomes (9)
Evaluate the incidence of neuropathy induced by study treatment (conventional paclitaxel vs nab-paclitaxel)
Measured: 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
Measured: Every 12 weeks up to 24 weeks
Determine the predictive value of genetic variants (SNPs) for the development of neuropathy
Measured: In the two weeks before start treatment
Determine the clinical activity of both treatments (response rate, time to progression)
Measured: Every 8-12 weeks up to 24 weeks
Determine toxicity profile and safety of study treatments (NCI-CTCAE v4.0)
Measured: Every 2 weeks up to 24 weeks
Determine time to neurotoxicity onset
Measured: Every 2 weeks up to 24 weeks
Determine time to recovery from neurotoxicity
Measured: Every 2 weeks up to 24 weeks
Determine time to progression
Measured: Every 8-12 weeks up to 24 weeks
Assess quality of live (EORTC QLQ-C30 and EORTC QLQ-CIPN20)
Measured: Every 4 weeks up to 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jan 2013 (estimated)
- Study startDec 2012
- Primary completionDec 2015
- Study completionDec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fundacion Oncosur
- Sponsor type
- Research network
- Responsible party
- Sponsor
- Investigators
- Eva Ciruelos, MD, Study director, Hospital 12 de Octubre, Servicio de Oncología MédicaNoelia Martínez, MD, Principal investigator, Hoapital Ramón y Cajal, Servicio de Oncología MédicaRafael Carrión, MD, Principal investigator, Hospital Universitario del Sureste, Servicio de Oncología MédicaJosé A García Sáenz, MD, Principal investigator, Hospital Clínico San Carlos, Servicio de Oncología MédicaMaría Echarri, Md, Principal investigator, Hospital Universitario Severo Ochoa, Servicio de Oncología MédicaBlanca Cantos, MD, Principal investigator, Hospital Universitario Puerta de hierro Majadahonda, Servicio de Oncología MédicaCoralía Bueno, MD, Principal investigator, Hospital Universitario Infanta Cristina, Servicio de Oncología MédicaMiguel A Lara, MD, Principal investigator, Hospital Universitario Infanta Leonor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01763710
- Sponsor's protocol ID
- ONCOSUR-2012-01
- Acronym
- neurabrax
- Status last verified
- Mar 2016
- First submitted
- 14 Dec 2012
- Last updated
- 29 Mar 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
Ciruelos E, Apellaniz-Ruiz M, Cantos B, Martinez-Janez N, Bueno-Muino C, Echarri MJ, Enrech S, Guerra JA, Manso L, Pascual T, Dominguez C, Gonzalo JF, Sanz JL, Rodriguez-Antona C, Sepulveda JM. A Pilot, Phase II, Randomized, Open-Label Clinical Trial Comparing the Neurotoxicity of Three Dose Regimens of Nab-Paclitaxel to That of Solvent-Based Paclitaxel as the First-Line Treatment for Patients with Human Epidermal Growth Factor Receptor Type 2-Negative Metastatic Breast Cancer. Oncologist. 2019 Nov;24(11):e1024-e1033. doi: 10.1634/theoncologist.2017-0664. Epub 2019 Apr 25.
PubMed 31023863
Study at a glance
From the registry record, last updated by the sponsor on 29 Mar 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neurotoxicity Characterization Phase II Randomized Study of Nab-paclitaxel Versus Conventional Paclitaxel as First-line Therapy of Metastatic HER2-negative Breast Cancer.
- ClinicalTrials.gov ID
- NCT01763710
- Acronym / sponsor ID
- neurabrax / ONCOSUR-2012-01
- Conditions
- Breast Cancer
- Keywords
- Breast cancer, Neurotoxicity
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Fundacion OncosurResearch network
- Study start
- Dec 2012
- Primary completion
- Dec 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 9 Jan 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Arm A | Active comparator | Drug: Paclitaxel 80 mg/m2Paclitaxel 80 mg/m2 days 1, 8 and 15 |
| Arm B | Experimental | Drug: Nab-paclitaxel 100 mg/m2 days 1, 8 and 15Nab-paclitaxel 100 mg/m2 days 1, 8 and 15 |
| Arm C | Experimental | Drug: Nab-paclitaxel 150 mg/m2 days 1, 8 and 15Nab-paclitaxel 150 mg/m2 days 1, 8 and 15 |
| Arm D | Experimental | Drug: Nab-paclitaxel 150 mg/m2 days 1 and 15Nab-paclitaxel 150 mg/m2 days 1 and 15 |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Women with histologically or cytologically of stage IV breast cancer.
- Non-candidate patient to trastuzumab or lapatinib treatment as not presenting HER2 oncogene amplification.
- Metastatic disease not previously treated with chemotherapy. It is allowed pre-treatment hormone with anti-target or bisphosphonates for advanced disease.
- Measurable or evaluable disease by RECIST criteria.
- Previous sensory neuropathy <= grade 1, according to NCI-CTCAE criteria, due to any reason.
Key exclusion criteria (9 listed)
- Prior chemotherapy treatment for metastatic disease.
- Brain metastases.
- Concomitant treatment with hormone therapy or immunotherapy for breast cancer, or during the two weeks prior to inclusion in the study.
- Any concomitant medical or psychiatric illness including active infection.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Paclitaxel 80 mg/m2Paclitaxel 80 mg/m2 days 1, 8 and 15 | Drug | Arm A |
| Nab-paclitaxel 100 mg/m2 days 1, 8 and 15Nab-paclitaxel 100 mg/m2 days 1, 8 and 15 | Drug | Arm B |
| Nab-paclitaxel 150 mg/m2 days 1, 8 and 15Nab-paclitaxel 150 mg/m2 days 1, 8 and 15 | Drug | Arm C |
| Nab-paclitaxel 150 mg/m2 days 1 and 15Nab-paclitaxel 150 mg/m2 days 1 and 15 | Drug | Arm D |
Primary outcome
TNS - Total Neuropathy Score
Time frame: Every 3 months up to 6 months
9 secondary outcomes
Evaluate the incidence of neuropathy induced by study treatment (conventional paclitaxel vs nab-paclitaxel)
Time frame: 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
Determine the predictive value of genetic variants (SNPs) for the development of neuropathy
Time frame: 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
Determine toxicity profile and safety of study treatments (NCI-CTCAE v4.0)
Time frame: Every 2 weeks up to 24 weeks
Determine time to neurotoxicity onset
Time frame: Every 2 weeks up to 24 weeks
Determine time to recovery from neurotoxicity
Time frame: Every 2 weeks up to 24 weeks
Determine time to progression
Time frame: 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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Mar 2016.
- Derived from this study: PubMed 31023863Ciruelos E, Apellaniz-Ruiz M, Cantos B, Martinez-Janez N, Bueno-Muino C, Echarri MJ, Enrech S, Guerra JA, Manso L, Pascual T, Dominguez C, Gonzalo JF, Sanz JL, Rodriguez-Antona C, Sepulveda JM. A Pilot, Phase II, Randomized, Open-Label Clinical Trial Comparing the Neurotoxicity of Three Dose Regimens of Nab-Paclitaxel to That of Solvent-Based Paclitaxel as the First-Line Treatment for Patients with Human Epidermal Growth Factor Receptor Type 2-Negative Metastatic Breast Cancer. Oncologist. 2019 Nov;24(11):e1024-e1033. doi: 10.1634/theoncologist.2017-0664. Epub 2019 Apr 25.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Eva Ciruelos, MD study director
Hospital 12 de Octubre, Servicio de Oncología Médica
Noelia Martínez, MD principal investigator
Hoapital Ramón y Cajal, Servicio de Oncología Médica
Rafael Carrión, MD principal investigator
Hospital Universitario del Sureste, Servicio de Oncología Médica
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Paclitaxel 80 mg/m2, Nab-paclitaxel 100 mg/m2 days 1, 8 and 15 and Nab-paclitaxel 150 mg/m2 days 1, 8 and 15 in people with Breast Cancer, run by Fundacion Oncosur at 10 sites in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Mar 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
TNS - Total Neuropathy Score (time frame: Every 3 months up to 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01763710, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Mar 2016.