Back to results

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

Primary Purpose

Breast Cancer

Status

Completed

Phase

Phase 2

Locations

Spain

Study Type

Interventional

Intervention

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

About this trial

This is an interventional diagnostic trial for Breast Cancer focused on measuring Breast cancer, Neurotoxicity

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

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.
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.

Exclusion Criteria:

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.
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).

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Experimental

Arm Label

Arm A

Arm B

Arm C

Arm D

Arm Description

Paclitaxel 80 mg/m2 days 1, 8 and 15

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

Outcomes

Primary Outcome Measures

TNS - Total Neuropathy Score

Secondary Outcome Measures

Evaluate the incidence of neuropathy induced by study treatment (conventional paclitaxel vs nab-paclitaxel)

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

Determine the predictive value of genetic variants (SNPs) for the development of neuropathy

Determine the clinical activity of both treatments (response rate, time to progression)

Determine toxicity profile and safety of study treatments (NCI-CTCAE v4.0)

Determine time to neurotoxicity onset

Determine time to recovery from neurotoxicity

Determine time to progression

Assess quality of live (EORTC QLQ-C30 and EORTC QLQ-CIPN20)

Full Information

NCT ID

NCT01763710

First Posted

December 14, 2012

Last Updated

March 28, 2016

Sponsor

Fundacion Oncosur

1. Study Identification

Unique Protocol Identification Number

NCT01763710

Brief Title

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

Acronym

neurabrax

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2016

Overall Recruitment Status

Completed

Study Start Date

December 2012 (undefined)

Primary Completion Date

December 2015 (Actual)

Study Completion Date

December 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Fundacion Oncosur

4. Oversight

Data Monitoring Committee

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Breast Cancer

Keywords

Breast cancer, Neurotoxicity

7. Study Design

Primary Purpose

Diagnostic

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

60 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm A

Arm Type

Active Comparator

Arm Description

Paclitaxel 80 mg/m2 days 1, 8 and 15

Arm Title

Arm B

Arm Type

Experimental

Arm Description

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

Arm Title

Arm C

Arm Type

Experimental

Arm Description

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

Arm Title

Arm D

Arm Type

Experimental

Arm Description

Nab-paclitaxel 150 mg/m2 days 1 and 15

Intervention Type

Drug

Intervention Name(s)

Paclitaxel 80 mg/m2

Intervention Description

Paclitaxel 80 mg/m2 days 1, 8 and 15

Intervention Type

Drug

Intervention Name(s)

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

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

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

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Nab-paclitaxel 150 mg/m2 days 1 and 15

Intervention Description

Nab-paclitaxel 150 mg/m2 days 1 and 15

Primary Outcome Measure Information:

Title

TNS - Total Neuropathy Score

Time Frame

Every 3 months up to 6 months

Secondary Outcome Measure Information:

Title

Evaluate the incidence of neuropathy induced by study treatment (conventional paclitaxel vs nab-paclitaxel)

Time Frame

Every 3 weeks up to 24 weeks

Title

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

Title

Determine the predictive value of genetic variants (SNPs) for the development of neuropathy

Time Frame

In the two weeks before start treatment

Title

Determine the clinical activity of both treatments (response rate, time to progression)

Time Frame

Every 8-12 weeks up to 24 weeks

Title

Determine toxicity profile and safety of study treatments (NCI-CTCAE v4.0)

Time Frame

Every 2 weeks up to 24 weeks

Title

Determine time to neurotoxicity onset

Time Frame

Every 2 weeks up to 24 weeks

Title

Determine time to recovery from neurotoxicity

Time Frame

Every 2 weeks up to 24 weeks

Title

Determine time to progression

Time Frame

Every 8-12 weeks up to 24 weeks

Title

Assess quality of live (EORTC QLQ-C30 and EORTC QLQ-CIPN20)

Time Frame

Every 4 weeks up to 24 weeks

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. 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. Exclusion Criteria: 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. 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).

Overall Study Officials: