Schedules of Nab-Paclitaxel in Metastatic Breast Cancer

Metastatic Breastcancer Clinical Trial

— SNAP  

Official title:

A Randomized Phase II Study Evaluating Different Schedules of Nab-Paclitaxel in Metastatic Breast Cancer (SNAP Trial)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01746225
• Other study ID #: IBCSG 42-12 / BIG 2-12
• Secondary ID: 2012-003058-10
• Status: Completed
• Phase: Phase 2
• Start date: April 2013
• Est. completion date: March 16, 2023

Study information

• Verified date: May 2023
• Source: ETOP IBCSG Partners Foundation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

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 Each of three arms will be compared to a historical reference of seven-month median progression-free survival (PFS) based on the most recent trial with docetaxel as control arm to determine whether any of the three arms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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 258
• Est. completion date: March 16, 2023
• Est. primary completion date: May 2016
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Neoplasms
• Metastatic Breastcancer

Intervention

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)

Locations

Country	Name	City	State
Belgium	CHR de la Citadelle, Oncology-Haematology Unit	Liège
Belgium	CHU Sart Tilman, Medical Oncology	Liège
Belgium	Centre Hospitalier Peltzer-La Tourelle, Department of Clinical Cancerology	Verviers
Ireland	Bon Secours	Cork
Ireland	Cork University Hospital	Cork
Ireland	Beaumont Hospital	Dublin
Ireland	Mater Misericordiae University Hospital	Dublin
Ireland	Mater Private Hospital	Dublin
Ireland	St James's Hospital	Dublin
Ireland	St Vincent's University Hospital	Dublin
Ireland	University Hospital Galway	Galway
Ireland	Mid-Western Regional Hospital	Limerick
Ireland	Waterford Regional Hospital	Waterford
Italy	Azienda Ospedaliera SS Antonio e Biagio	Alessandria
Italy	Ospedale degli Infermi	Biella
Italy	IRCCS MultiMedica	Castellanza
Italy	E.O. Ospedali Galliera	Genova
Italy	Istituto Europeo di Oncologia (IEO)	Milano
Italy	Uo Medicina Ocologica Ospedale Di Carpri e Mirandola, Azienda USL di Modena	Modena
Italy	Fondazione Salvatore Maugeri	Pavia
Italy	U.O. Oncologia, AUSL Rimini	Rimini
Italy	Universita degli Studi di Roma La Sapienza	Roma
Italy	Azienda Osp. Universitaria di Udine	Udine
Italy	Ospedale di Circolo e Fondatione Macchi	Varese
Slovenia	Institute of Oncology	Ljubljana
Spain	Hospital Universitari Vall D'Hebron	Barcelona
Spain	Consorcop Hospitalario Provincial De Castellon	Castelló
Spain	Hospital Universitari Arnau De Vilanova De Lleida	Lleida
Spain	Hospital Universitari Sant Joan De Reus	Tarragona
Spain	Hospital Universitario Lozano Blesa De Zaragoza	Zaragoza
Switzerland	Kantonsspital Aarau	Aarau
Switzerland	Universitätsspital Basel	Basel
Switzerland	Instituto Oncologico della Svizzera Italiana	Bellinzona
Switzerland	Universitätsspital/ Inselspital Bern	Bern
Switzerland	Spitalzentrum Biel	Biel
Switzerland	Kantonsspital Graubünden	Chur
Switzerland	Kantonsspital Baselland	Liestal
Switzerland	Luzerner Kantonsspital	Luzern
Switzerland	Kantonsspital St. Gallen	St. Gallen
Switzerland	Onkologiezentrum Thun-Berner Oberland	Thun
Switzerland	Kantonsspital Winterthur	Winterthur

Sponsors (2)

Lead Sponsor	Collaborator
ETOP IBCSG Partners Foundation	Breast International Group

Countries where clinical trial is conducted

Belgium,  Ireland,  Italy,  Slovenia,  Spain,  Switzerland, 

References & Publications (4)

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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival	Time from randomization until objective disease progression [progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions] or death, whichever occurs first. For patients without progression, follow-up was censored at the date of last disease assessment without progression, unless death occurred within a short period of time (12 weeks) following the date last known progression-free, in which case the death was counted as a PFS event.	Reported after 18.2 months median follow-up since randomization
Secondary	Feasibility of Treatment: Number of Participants Completed Treatment According to the Protocol for at Least 24 Weeks	Whether or not the patient completed treatment according to the protocol for at least 24 weeks. Patients who progressed within 24 weeks were considered as not completing.	Baseline to 24 weeks follow-up
Secondary	Disease Control: Overall Response of Stable Disease for a Duration of =24 Weeks	Overall response of stable disease (or non-CR/non-PD for patients with non-measurable disease) for a duration of =24 weeks, or better (i.e., partial or complete response) according to RECIST criteria [Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.]	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
Secondary	Best Overall Response	Best response according to RECIST 1.1 criteria [assessed by MRI] recorded from the start of treatment across all time points until end of study treatment. Confirmation of partial or complete response by an additional scan was not requested in this trial.	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
Secondary	Overall Survival	Time from randomization until death from any cause, or censored at date last known alive	Reported after 18.2 months median follow-up since randomization
Secondary	Changes in Physical Well-being (Change From Day 1 of Cycle 4 to Day 1 of Cycle 6)	Primary quality of life=physical well being; endpoint based on the GLQ 8. The indicator was in Linear Analogue Self-Assessment (LASA) format ranging 0-100 (0=as bad as it can be, 100=as good as it can be).	Assessed from day 1 of cycle 4 through day 1 of cycle 12