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

NCT01763710 | Completed Phase 2

• 1 other identifier: ONCOSUR-2012-01
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 10

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.

Conditions

Breast Cancer

Keywords

Breast cancer; Neurotoxicity

Outcome Measures

Primary Outcomes (1)

• TNS - Total Neuropathy Score

  Every 3 months up to 6 months

Secondary Outcomes (9)

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

  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

  Every 12 weeks up to 24 weeks

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

  In the two weeks before start treatment

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

  Every 8-12 weeks up to 24 weeks

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

  Every 2 weeks up to 24 weeks

Study Arms (4)

Arm A

ACTIVE COMPARATOR

Paclitaxel 80 mg/m2 days 1, 8 and 15

Drug: Paclitaxel 80 mg/m2

Arm B

EXPERIMENTAL

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

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

Arm C

EXPERIMENTAL

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

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

Arm D

EXPERIMENTAL

Nab-paclitaxel 150 mg/m2 days 1 and 15

Drug: Nab-paclitaxel 150 mg/m2 days 1 and 15

Interventions

Paclitaxel 80 mg/m2 DRUG

Paclitaxel 80 mg/m2 days 1, 8 and 15

Arm A

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

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

Arm B

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

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

Arm C

Nab-paclitaxel 150 mg/m2 days 1 and 15 DRUG

Nab-paclitaxel 150 mg/m2 days 1 and 15

Arm D

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Prior chemotherapy treatment for metastatic disease.
• Brain metastases.
• 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.

Sponsors & Collaborators

• Fundacion Oncosur: lead

Study Sites (10)

Hospital Universitario Del Sureste

Arganda, Madrid, 28500, Spain

Location

Hospital Universitario de Fuenlabrada

Fuenlabrada, Madrid, 28942, Spain

Location

Hospital Universitario de Getafe

Getafe, Madrid, 28905, Spain

Location

Hospital Universitario Severo Ochoa

Leganés, Madrid, 28911, Spain

Location

Hospital Universitario Infanta Leonor

Madrid, Madrid, 28031, Spain

Location

Hospital Ramón Y Cajal

Madrid, Madrid, 28034, Spain

Location

Hospital Clínico San Carlos

Madrid, Madrid, 28040, Spain

Location

Hospital 12 de Octubre

Madrid, Madrid, Spain

Location

Hospital Universitario Puerta de Hierro Majadahonda

Majadahonda, Madrid, 28222, Spain

Location

Hospital Universitario Infanta Cristina

Parla, Madrid, 28981, Spain

Location

Related Publications (1)

• 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.

  PMID: 31023863 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Neurotoxicity Syndromes

Interventions

Paclitaxel; 130-nm albumin-bound paclitaxel

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Nervous System Diseases; Poisoning; Chemically-Induced Disorders

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Eva Ciruelos, MD

  Hospital 12 de Octubre, Servicio de Oncología Médica

  STUDY DIRECTOR

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 14, 2012
• First Posted: January 9, 2013
• Study Start: December 1, 2012
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: March 29, 2016

Record last verified: 2016-03

Locations

ES (10)