Schedules of Nab-Paclitaxel in Metastatic Breast Cancer (SNAP)

This study is currently recruiting participants.
Verified October 2013 by International Breast Cancer Study Group
Sponsor:
Information provided by (Responsible Party):
International Breast Cancer Study Group
ClinicalTrials.gov Identifier:
NCT01746225
First received: November 28, 2012
Last updated: October 30, 2013
Last verified: October 2013
  Purpose

Longer first line chemotherapy duration has recently been associated with a modest, but significant improvement in overall survival and a clinically meaningful and statistically significant improvement in progression-free survival, in metastatic breast cancer patients. Prolonging chemotherapy until disease progression, however, must be weighed against the detrimental effects of continuous chemotherapy delivery. The SNAP trial seeks to improve the tolerability of prolonged chemotherapy administration strategy by studying alternative treatment schedules, while preserving and possibly improving treatment efficacy in this disease setting.

The availability of a new nanoparticle albumin-bound taxane, nab-Paclitaxel (Abraxane®), represents an opportunity to test this hypothesis. Nab-Paclitaxel has been developed in an attempt to reduce the toxicity associated with standard taxane administration (caused by the use of chemical solvents) while increasing antitumor efficacy.

The SNAP randomized phase II trial evaluates three schedules of nab-Paclitaxel as prolonged chemotherapy administration strategy. Each of three arms will be compared to a historical reference of seven-month median progression-free survival (PFS) based on the most recent trial with docetaxel as control arm to determine whether any of the three arms are worthy of further investigation.


Condition Intervention Phase
Metastatic Breast Cancer.
Drug: nab-Paclitaxel
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Phase II Study Evaluating Different Schedules of Nab-Paclitaxel in Metastatic Breast Cancer (SNAP Trial)

Resource links provided by NLM:


Further study details as provided by International Breast Cancer Study Group:

Primary Outcome Measures:
  • Efficacy of nab-Paclitaxel schedules [ Time Frame: At the end of the third induction cycle and during maintenace nab-Paclitaxel every three months until PD (an expected average of nine months) ] [ Designated as safety issue: No ]
    Disease response and progression will be evaluated according to the revised Response Evaluation Criteria in Solid Tumors (RECIST V 1.1) Patients may have measurable or non-measurable disease. CT can is the method to measure lesion.


Secondary Outcome Measures:
  • Tolerability, feasibility, disease response and OS of nab-Paclitaxel schedules [ Time Frame: Targeted AEs at the end of each cycle and hematology days 1, 8, 15, 22 according to treatment arm ] [ Designated as safety issue: Yes ]
    Determination of targeted adverse events (AE), performance status, hematological/ biochemical examinations and physical exams are used to evaluate tolerability and feasibility, vital signs for overall survival (OS).

  • Quality of life [ Time Frame: QL self-assessment once each months until PD (maximal twelve months, expected average of nine months) and at end-of-treatment visit ] [ Designated as safety issue: No ]
    To explore the changes in quality of life (QL) over time until treatment discontinuation.

  • Prognostic biomarker analysis [ Time Frame: SPARC and caveolin expressions will be determined in FFPE (formalin fixed paraffin embedded) samples from primary tumor (obtained 14 days prior to randomization) and from FFPE sample of metastatic biopsy at PD (an expected average of nine months) ] [ Designated as safety issue: No ]
    To investigate the prognostic role of putative markers (SPARC and caveolin) and assess any change in the expression of SPARC and caveolin between primary and the metastatic sites.


Estimated Enrollment: 240
Study Start Date: April 2013
Estimated Study Completion Date: April 2023
Estimated Primary Completion Date: April 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: nab-Paclitaxel 150 mg/m2 days 1,15
Arm A: Induction nab-Paclitaxel 150 mg/m2 on days 1,8,15 every 28 days for 3 cycles followed by maintenance nab-Paclitaxel 150 mg/m2 administered on days 1, 15 of each 28-day cycle (total 300mg/m2 per cycle) until progression or unacceptable toxicity.
Drug: nab-Paclitaxel
Induction phase: 3 cycles of nab-Paclitaxel days 1, 8, 15. Maintenance phase with three maintenance schedules of nab-Paclitaxel (same total dose per cycle, different number of administrations)
Other Name: Abraxane
Experimental: nab-Paclitaxel 100 mg/m2 days 1,8,15
Arm B: Induction nab-Paclitaxel 150 mg/m2 on days 1,8,15 every 28 days for 3 cycles followed by maintenance nab-Paclitaxel 100 mg/m2 administered on days 1, 8, 15 of each 28-day cycle (total 300mg/m2 per cycle) until progression or unacceptable toxicity.
Drug: nab-Paclitaxel
Induction phase: 3 cycles of nab-Paclitaxel days 1, 8, 15. Maintenance phase with three maintenance schedules of nab-Paclitaxel (same total dose per cycle, different number of administrations)
Other Name: Abraxane
Experimental: nab-Paclitaxel 75 mg/m2 days 1,8,15,22
Arm C: Induction nab-Paclitaxel 150 mg/m2 on days 1,8,15 every 28 days for 3 cycles followed by maintenance nab-Paclitaxel 75 mg/m2 administered on days 1, 8, 15, 22 of each 28-day cycle (total 300mg/m2 per cycle) until progression or unacceptable toxicity.
Drug: nab-Paclitaxel
Induction phase: 3 cycles of nab-Paclitaxel days 1, 8, 15. Maintenance phase with three maintenance schedules of nab-Paclitaxel (same total dose per cycle, different number of administrations)
Other Name: Abraxane

  Eligibility

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

Inclusion Criteria:

  • Histologically or cytologically confirmed HER2-negative metastatic (stage IV) breast cancer.
  • Measurable or non-measurable, but radiologically evaluable, disease according to RECIST 1.1 criteria.
  • Female aged 18 years or older.
  • Life expectancy > 3 months.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
  • Either ER-positive or ER-negative disease. Patients with ER-positive disease must be endocrine resistant, defined as having failed at least one prior endocrine therapy for breast cancer, or must be candidates for first-line chemotherapy.
  • If previously treated with a taxane or anthracycline in the neoadjuvant or adjuvant setting, the period from end of treatment to disease recurrence must have been > 12 months (> 365 days).
  • Radiation therapy, if given and regardless of site, must be completed at least 2 weeks prior to randomization.
  • Normal hematologic status.
  • Normal renal function.
  • Normal liver function.
  • Normal cardiac function.
  • Women of childbearing potential: documented negative pregnancy test within 2 weeks prior to randomization, and acceptable birth control during the duration of the trial therapy and for a period of 6 months following the last administration of study drug.
  • Written Informed Consent (IC) must be signed and dated by the patient and the Investigator prior to randomization.
  • Completed baseline Quality of Life Form.
  • The patient has been informed of and agrees to data transfer and handling, in accordance with national data protection guidelines.
  • Availability of an formalin fixed paraffin embedded (FFPE) block from the primary tumor (breast lesion) for submission to central pathology review and for translational research.
  • Written consent to pathology material submission, signed and dated by the patient and the Investigator prior to randomization.

Exclusion Criteria:

  • Any prior chemotherapy for metastatic breast cancer.
  • Presence of central nervous system (CNS) metastasis.
  • Peripheral neuropathy grade 2 or higher (CTCAE version 4).
  • Significant uncontrolled cardiac disease (i.e. unstable angina, recent myocardial infarction within prior 6 months), patients classified as having a New York Heart Association (NYHA) class III or IV congestive heart failure.
  • Pregnant or lactating.
  • Prior history of non-breast malignancy (except for adequately controlled basal cell carcinoma of the skin, carcinoma in situ of the cervix, in situ carcinoma of the bladder).
  • Any concurrent condition which in the Investigator's opinion makes it inappropriate for the patient to participate in the trial or which would jeopardize compliance with the protocol.
  • Contraindications or known hypersensitivity to the study medication or excipients.
  • The use of any anti-cancer investigational agents within 30 days prior to expected start of trial treatment.
  • Inability or unwillingness to abide by the study protocol or cooperate fully with the Investigator.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01746225

Locations
Belgium
CHU Sart Tilman, Medical Oncology Recruiting
Liège, Belgium, 4000
Contact: Guy Jerusalem, MD, PhD    +32 43 667 664    g.jerusalem@chu.ulg.ac.be   
Principal Investigator: Guy Jerusalem, MD, PhD         
CHR de la Citadelle, Oncology-Haematology Unit Not yet recruiting
Liège, Belgium, 4000
Contact: Jean Paul Salmon, Dr    +32 42 25 64 45    jean.paul.salmon@chrcitadelle.be   
Principal Investigator: Jean Paul Salmon, Dr         
Centre Hospitalier Peltzer-La Tourelle, Department of Clinical Cancerology Recruiting
Verviers, Belgium, 4800
Contact: Annelore Barbeaux, MD    +32 87 21 94 83    annelore.barbeaux@chplt.be   
Principal Investigator: Annelore Barbeaux, MD         
Ireland
Mater Private Hospital Recruiting
Dublin, Ireland
Contact: Catherine Kelly       ckelly@mater.ie   
Principal Investigator: Catherine Kelly         
St James's Hospital Recruiting
Dublin, Ireland
Contact: John Kennedy       jkennedy@stjames.ie   
Principal Investigator: John Kennedy         
St Vincent's University Hospital Recruiting
Dublin, Ireland
Contact: Janice Walshe       janice.walshe@amnch.ie   
Principal Investigator: Janice Walshe         
Beaumont Hospital Recruiting
Dublin, Ireland
Contact: Bryan Hennessy       bryan.hennessy@hse.ie   
Principal Investigator: Bryan Hennessy         
Mater Misericordiae University Hospital Recruiting
Dublin, Ireland
Contact: Catherine Kelly       ckelly@mater.ie   
Principal Investigator: Catherine Kelly         
Mid-Western Regional Hospital Recruiting
Limerick, Ireland
Contact: Linda Coate       lindae.coate@hse.ie   
Principal Investigator: Linda Coate         
Waterford Regional Hospital Recruiting
Waterford, Ireland
Contact: Miriam O'Connor       Miriam.OConnor2@hse.ie   
Principal Investigator: Miriam O'Connor         
Italy
Azienda Ospedaliera SS Antonio e Biagio Not yet recruiting
Alessandria, Italy, 15121
Contact: Pierluigi Piovano       plpiovano@ospedale.al.it   
Principal Investigator: Pierluigi Piovano         
Ospedale degli Infermi Not yet recruiting
Biella, Italy, 13900
Contact: Alice Giacobino       alice.giacobino@poloncologico.org   
Principal Investigator: Alice Giacobino         
Ospedale "B. Ramazzini" Not yet recruiting
Carpi/ Modena, Italy, 41012
Contact: Fabrizio Artioli       f.artioli@ausl.mo.it   
Principal Investigator: Fabrizio Artioli         
E.O. Ospedali Galliera Not yet recruiting
Genova, Italy, 16128
Contact: Alessandra Gennari       alessandra.gennari@galliera.it   
Principal Investigator: Alessandra Gennari         
Istituto Europeo di Oncologia (IEO) Recruiting
Milano, Italy
Contact: Marco Colleoni       marco.colleoni@ieo.it   
Principal Investigator: Marco Colleoni         
Fondazione Salvatore Maugeri Not yet recruiting
Pavia, Italy, 27100
Contact: Lorenzo Pavesi       lorenzo.pavesi@fsm.it   
Principal Investigator: Lorenzo Pavesi         
Universita degli Studi di Roma La Sapienza Not yet recruiting
Roma, Italy, 00161
Contact: Giuseppe Naso       giuseppe.naso@uniroma1.it   
Principal Investigator: Giuseppe Naso         
Istituto Clinico Humanitas Not yet recruiting
Rozzano, Italy, 20089
Contact: Armando Santoto       armando.santoro@humanitas.it   
Principal Investigator: Armando Santoro         
IRCCS MultiMedica Not yet recruiting
Sede di Castellanza, Italy, 21053
Contact: Elisa Gallerani       Elisa.Gallerani@multimedica.it   
Principal Investigator: Elisa Gallerani         
Azienda Osp. Universitaria di Udine Not yet recruiting
Udine, Italy, 33100
Contact: Fabio Puglisi       fabio.puglisi@uniud.it   
Principal Investigator: Fabio Puglisi         
Slovenia
Institute of Oncology Recruiting
Ljubljana, Slovenia, 1000
Contact: Simona Borstnar       sborstnar@onko-i.si   
Principal Investigator: Simona Borstnar         
Switzerland
Universitätsspital Basel Recruiting
Basel, Switzerland, 4031
Contact: Christoph Rochlitz       Christoph.Rochlitz@usb.ch   
Principal Investigator: Christoph Rochlitz         
Instituto Oncologico della Svizzera Italiana Not yet recruiting
Bellinzona, Switzerland, 6500
Contact: Olivia Pagani       olivia.pagani@ibcsg.org   
Principal Investigator: Olivia Pagani         
Universitätsspital/ Inselspital Bern Recruiting
Bern, Switzerland, 3011
Contact: Manuela Rabaglio       manuela.rabaglio@insel.ch   
Principal Investigator: Manuela Rabaglio         
Spitalzentrum Biel Recruiting
Biel, Switzerland, 2501
Contact: Markus Borner       markus.borner@szb-chb.ch   
Principal Investigator: Markus Borner         
Kantonsspital Graubünden Recruiting
Chur, Switzerland, 7000
Contact: Roger von Moos       roger.vonmoos@ksgr.ch   
Principal Investigator: Roger von Moos         
Luzerner Kantonsspital Not yet recruiting
Luzern, Switzerland, 6000
Contact: Stefan Aebi       stefan.aebi@onkologie.ch   
Principal Investigator: Stefan Aebi         
Kantonsspital St. Gallen Recruiting
St. Gallen, Switzerland, 9007
Contact: Ursula Hasler-Strub       ursula.hasler-strub@kssg.ch   
Principal Investigator: Ursula Hasler-Strub         
Onkologiezentrum Thun-Berner Oberland Recruiting
Thun, Switzerland, 3600
Contact: Rauch Daniel       daniel.rauch@spitalstsag.ch   
Principal Investigator: Daniel Rauch         
Kantonsspital Winterthur Recruiting
Witerthur, Switzerland, 8401
Contact: Andreas Mueller       andreas.mueller@ksw.ch   
Principal Investigator: Andreas Mueller         
Sponsors and Collaborators
International Breast Cancer Study Group
Investigators
Study Chair: Alessandra Gennari, MD Division of Medical Oncology, E.O. Galliera, Genoa, Italy
Study Chair: Guy Jerusalem, MD, PhD CHU Sart Tilman and University of Liège, Liège, Belgium
  More Information

Publications:
Responsible Party: International Breast Cancer Study Group
ClinicalTrials.gov Identifier: NCT01746225     History of Changes
Other Study ID Numbers: IBCSG 42-12/BIG 2-12, 2012-003058-10
Study First Received: November 28, 2012
Last Updated: October 30, 2013
Health Authority: Switzerland: Swissmedic
Belgium: Federal Agency for Medicinal Products and Health Products
Italy: The Italian Medicines Agency
Ireland: Irish Medicines Board
Slovenia: Agency for Medicinal Products - Ministry of Health

Keywords provided by International Breast Cancer Study Group:
Metastatic
Breast
Cancer
HER2-negative Stage IV
No previous chemotherapy

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 16, 2014