Clinical trial NCT01746225: Schedules of Nab-Paclitaxel in Metastatic Breast Cancer
Official title: A Randomized Phase II Study Evaluating Different Schedules of Nab-Paclitaxel in Metastatic Breast Cancer (SNAP Trial)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Breastcancer
Keywords: Metastatic
Breast
Cancer
HER2-negative Stage IV
No previous chemotherapy
Lead sponsor: ETOP IBCSG Partners Foundation
Sponsor class: NETWORK
Collaborators: name: Breast International Group
First posted: 2012-12-10
Enrollment: 258
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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 Each of three arms will be compared to a historical reference of seven-month median progression-free survival (PFS) based on the most recent trial with docetaxel as control arm to determine whether any of the three arms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.


Eligibility 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.

Primary outcomes:
measure: Progression-free Survival
timeFrame: Reported after 18.2 months median follow-up since randomization
Secondary outcomes:
measure: Feasibility of Treatment: Number of Participants Completed Treatment According to the Protocol for at Least 24 Weeks
timeFrame: Baseline to 24 weeks follow-up
measure: Disease Control: Overall Response of Stable Disease for a Duration of ≥24 Weeks
timeFrame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 18 months
measure: Best Overall Response
timeFrame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 18 months
measure: Overall Survival
timeFrame: Reported after 18.2 months median follow-up since randomization
measure: Changes in Physical Well-being (Change From Day 1 of Cycle 4 to Day 1 of Cycle 6)
timeFrame: Assessed from day 1 of cycle 4 through day 1 of cycle 12
Other outcomes:
Locations:
city: Liège
country: Belgium
facility: CHR de la Citadelle, Oncology-Haematology Unit
city: Liège
country: Belgium
facility: CHU Sart Tilman, Medical Oncology
city: Verviers
country: Belgium
facility: Centre Hospitalier Peltzer-La Tourelle, Department of Clinical Cancerology
city: Cork
country: Ireland
facility: Bon Secours
city: Cork
country: Ireland
facility: Cork University Hospital
city: Dublin
country: Ireland
facility: Beaumont Hospital
city: Dublin
country: Ireland
facility: Mater Misericordiae University Hospital
city: Dublin
country: Ireland
facility: Mater Private Hospital
city: Dublin
country: Ireland
facility: St James's Hospital
city: Dublin
country: Ireland
facility: St Vincent's University Hospital
city: Galway
country: Ireland
facility: University Hospital Galway
city: Limerick
country: Ireland
facility: Mid-Western Regional Hospital
city: Waterford
country: Ireland
facility: Waterford Regional Hospital
city: Alessandria
country: Italy
facility: Azienda Ospedaliera SS Antonio e Biagio
city: Biella
country: Italy
facility: Ospedale degli Infermi
city: Castellanza
country: Italy
facility: IRCCS MultiMedica
city: Genova
country: Italy
facility: E.O. Ospedali Galliera
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia (IEO)
city: Modena
country: Italy
facility: Uo Medicina Ocologica Ospedale Di Carpri e Mirandola, Azienda USL di Modena
city: Pavia
country: Italy
facility: Fondazione Salvatore Maugeri
city: Rimini
country: Italy
facility: U.O. Oncologia, AUSL Rimini
city: Roma
country: Italy
facility: Universita degli Studi di Roma La Sapienza
city: Udine
country: Italy
facility: Azienda Osp. Universitaria di Udine
city: Varese
country: Italy
facility: Ospedale di Circolo e Fondatione Macchi
city: Ljubljana
country: Slovenia
facility: Institute of Oncology
city: Barcelona
country: Spain
facility: Hospital Universitari Vall D'Hebron
city: Castelló
country: Spain
facility: Consorcop Hospitalario Provincial De Castellon
city: Lleida
country: Spain
facility: Hospital Universitari Arnau De Vilanova De Lleida
city: Tarragona
country: Spain
facility: Hospital Universitari Sant Joan De Reus
city: Zaragoza
country: Spain
facility: Hospital Universitario Lozano Blesa De Zaragoza
city: Aarau
country: Switzerland
facility: Kantonsspital Aarau
city: Basel
country: Switzerland
facility: Universitätsspital Basel
city: Bellinzona
country: Switzerland
facility: Instituto Oncologico della Svizzera Italiana
city: Bern
country: Switzerland
facility: Universitätsspital/ Inselspital Bern
city: Biel
country: Switzerland
facility: Spitalzentrum Biel
city: Chur
country: Switzerland
facility: Kantonsspital Graubünden
city: Liestal
country: Switzerland
facility: Kantonsspital Baselland
city: Luzern
country: Switzerland
facility: Luzerner Kantonsspital
city: St. Gallen
country: Switzerland
facility: Kantonsspital St. Gallen
city: Thun
country: Switzerland
facility: Onkologiezentrum Thun-Berner Oberland
city: Winterthur
country: Switzerland
facility: Kantonsspital Winterthur
Study officials:
affiliation: Division of Medical Oncology, E.O. Galliera, Genoa, Italy
name: Alessandra Gennari, MD
role: STUDY_CHAIR
affiliation: CHU Sart Tilman and University of Liège, Liège, Belgium
name: Guy Jerusalem, MD, PhD
role: STUDY_CHAIR
References:
citation: Chia SK, Speers CH, D'yachkova Y, Kang A, Malfair-Taylor S, Barnett J, Coldman A, Gelmon KA, O'reilly SE, Olivotto IA. The impact of new chemotherapeutic and hormone agents on survival in a population-based cohort of women with metastatic breast cancer. Cancer. 2007 Sep 1;110(5):973-9. doi: 10.1002/cncr.22867.
citation: Gennari A, Conte P, Rosso R, Orlandini C, Bruzzi P. Survival of metastatic breast carcinoma patients over a 20-year period: a retrospective analysis based on individual patient data from six consecutive studies. Cancer. 2005 Oct 15;104(8):1742-50. doi: 10.1002/cncr.21359.
citation: Andre F, Slimane K, Bachelot T, Dunant A, Namer M, Barrelier A, Kabbaj O, Spano JP, Marsiglia H, Rouzier R, Delaloge S, Spielmann M. Breast cancer with synchronous metastases: trends in survival during a 14-year period. J Clin Oncol. 2004 Aug 15;22(16):3302-8. doi: 10.1200/JCO.2004.08.095.
citation: Dawood S, Broglio K, Gonzalez-Angulo AM, Buzdar AU, Hortobagyi GN, Giordano SH. Trends in survival over the past two decades among white and black patients with newly diagnosed stage IV breast cancer. J Clin Oncol. 2008 Oct 20;26(30):4891-8. doi: 10.1200/JCO.2007.14.1168. Epub 2008 Aug 25.
citation: Gennari A, Sun Z, Hasler-Strub U, Colleoni M, Kennedy MJ, Von Moos R, Cortes J, Vidal MJ, Hennessy B, Walshe J, Parraga KA, Ribi K, Bernhard J, Murillo SM, Pagani O, Barbeaux A, Borstnar S, Rabaglio-Poretti M, Maibach R, Regan MM, Jerusalem G; International Breast Cancer Study Group, Cancer Trials Ireland and SOLTI Group. A randomized phase II study evaluating different maintenance schedules of nab-paclitaxel in the first-line treatment of metastatic breast cancer: final results of the IBCSG 42-12/BIG 2-12 SNAP trial. Ann Oncol. 2018 Mar 1;29(3):661-668. doi: 10.1093/annonc/mdx772.