Schedules of Nab-Paclitaxel in Metastatic Breast Cancer

NCT ID: NCT01746225

Last Updated: 2023-06-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 258 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-04-30
• Study Completion Date: 2023-03-16

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 Each of three arms will be compared to a historical reference of seven-month median progression-free survival (PFS) based on the most recent trial with docetaxel as control arm to determine whether any of the three arms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

Conditions

Metastatic Breastcancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

A: nab-Paclitaxel 150 mg/m2 days 1,15

Arm A: Induction* nab-Paclitaxel 125 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.

*Following Amendment 1, the dose in the induction phase dose in all three arms was reduced to 125 mg/m² from 150 mg/m².

Group Type: EXPERIMENTAL

nab-Paclitaxel

Intervention Type: DRUG

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)

B: nab-Paclitaxel 100 mg/m2 days 1,8,15

Arm B: Induction* nab-Paclitaxel 125 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.

*Following Amendment 1, the dose in the induction phase dose in all three arms was reduced to 125 mg/m² from 150 mg/m².

Group Type: EXPERIMENTAL

nab-Paclitaxel

Intervention Type: DRUG

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)

C: nab-Paclitaxel 75 mg/m2 days 1,8,15,22

Arm C: Induction* nab-Paclitaxel 125 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.

*Following Amendment 1, the dose in the induction phase dose in all three arms was reduced to 125 mg/m² from 150 mg/m².

Group Type: EXPERIMENTAL

nab-Paclitaxel

Intervention Type: DRUG

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)

Interventions

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)

Intervention Type: DRUG

Other Intervention Names

Abraxane

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Breast International Group

OTHER

Sponsor Role: collaborator

ETOP IBCSG Partners Foundation

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Alessandra Gennari, MD

Role: STUDY_CHAIR

Division of Medical Oncology, E.O. Galliera, Genoa, Italy

Guy Jerusalem, MD, PhD

Role: STUDY_CHAIR

CHU Sart Tilman and University of Liège, Liège, Belgium

Locations

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, , Belgium

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, , Ireland

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)

Milan, , 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, , Italy

Institute of Oncology

Ljubljana, , Slovenia

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, , Spain

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

Lucerne, , Switzerland

Kantonsspital St. Gallen

Sankt Gallen, , Switzerland

Onkologiezentrum Thun-Berner Oberland

Thun, , Switzerland

Kantonsspital Winterthur

Winterthur, , Switzerland

Countries

Belgium; Ireland; Italy; Slovenia; Spain; Switzerland

References

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.

Reference Type: BACKGROUND

PMID: 17647245 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 16149088 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 15310773 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 18725649 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 29228091 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2012-003058-10

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

IBCSG 42-12 / BIG 2-12

Identifier Type: -

Identifier Source: org_study_id