Schedules of Nab-Paclitaxel in Metastatic Breast Cancer

NCT01746225 | Completed Phase 2 Results DMC

• 2 other identifiers: IBCSG 42-12 / BIG 2-122012-003058-10
• Study Type: interventional
• Target: 258
• Locations: 6 countries
• Sites: 41

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 Each of three arms will be compared to a historical reference of seven-month median progression-free survival (PFS) based on the most recent trial with docetaxel as control arm to determine whether any of the three arms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

Keywords

Metastatic; Breast; Cancer; HER2-negative Stage IV; No previous chemotherapy

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Feasibility of Treatment: Number of Participants Completed Treatment According to the Protocol for at Least 24 Weeks

  Baseline to 24 weeks follow-up

• Disease Control: Overall Response of Stable Disease for a Duration of ≥24 Weeks

  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

• Best Overall Response

  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

• Overall Survival

  Reported after 18.2 months median follow-up since randomization

• Changes in Physical Well-being (Change From Day 1 of Cycle 4 to Day 1 of Cycle 6)

  Assessed from day 1 of cycle 4 through day 1 of cycle 12

Study Arms (3)

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

EXPERIMENTAL

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.

Drug: nab-Paclitaxel

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

EXPERIMENTAL

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.

Drug: nab-Paclitaxel

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

EXPERIMENTAL

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.

Drug: nab-Paclitaxel

Interventions

nab-Paclitaxel 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)

Also known as: Abraxane

A: nab-Paclitaxel 150 mg/m2 days 1,15; B: nab-Paclitaxel 100 mg/m2 days 1,8,15; C: nab-Paclitaxel 75 mg/m2 days 1,8,15,22

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• ETOP IBCSG Partners Foundation: lead
• Breast International Group: collaborator

Study Sites (41)

CHR de la Citadelle, Oncology-Haematology Unit

Liège, 4000, Belgium

Location

CHU Sart Tilman, Medical Oncology

Liège, 4000, Belgium

Location

Centre Hospitalier Peltzer-La Tourelle, Department of Clinical Cancerology

Verviers, 4800, Belgium

Location

Bon Secours

Cork, Ireland

Location

Cork University Hospital

Cork, Ireland

Location

Beaumont Hospital

Dublin, Ireland

Location

Mater Misericordiae University Hospital

Dublin, Ireland

Location

Mater Private Hospital

Dublin, Ireland

Location

St James's Hospital

Dublin, Ireland

Location

St Vincent's University Hospital

Dublin, Ireland

Location

University Hospital Galway

Galway, Ireland

Location

Mid-Western Regional Hospital

Limerick, Ireland

Location

Waterford Regional Hospital

Waterford, Ireland

Location

Azienda Ospedaliera SS Antonio e Biagio

Alessandria, 15121, Italy

Location

Ospedale degli Infermi

Biella, 13900, Italy

Location

IRCCS MultiMedica

Castellanza, 21053, Italy

Location

E.O. Ospedali Galliera

Genova, 16128, Italy

Location

Istituto Europeo di Oncologia (IEO)

Milan, Italy

Location

Uo Medicina Ocologica Ospedale Di Carpri e Mirandola, Azienda USL di Modena

Modena, 41012, Italy

Location

Fondazione Salvatore Maugeri

Pavia, 27100, Italy

Location

U.O. Oncologia, AUSL Rimini

Rimini, 47923, Italy

Location

Universita degli Studi di Roma La Sapienza

Roma, 00161, Italy

Location

Azienda Osp. Universitaria di Udine

Udine, 33100, Italy

Location

Ospedale di Circolo e Fondatione Macchi

Varese, 21100, Italy

Location

Institute of Oncology

Ljubljana, 1000, Slovenia

Location

Hospital Universitari Vall D'Hebron

Barcelona, Spain

Location

Consorcop Hospitalario Provincial De Castellon

Castelló, 12002, Spain

Location

Hospital Universitari Arnau De Vilanova De Lleida

Lleida, 25198, Spain

Location

Hospital Universitari Sant Joan De Reus

Tarragona, 43204, Spain

Location

Hospital Universitario Lozano Blesa De Zaragoza

Zaragoza, 50009, Spain

Location

Kantonsspital Aarau

Aarau, 5001, Switzerland

Location

Universitätsspital Basel

Basel, 4031, Switzerland

Location

Instituto Oncologico della Svizzera Italiana

Bellinzona, 6500, Switzerland

Location

Universitätsspital/ Inselspital Bern

Bern, 3011, Switzerland

Location

Spitalzentrum Biel

Biel, 2501, Switzerland

Location

Kantonsspital Graubünden

Chur, 7000, Switzerland

Location

Kantonsspital Baselland

Liestal, 4410, Switzerland

Location

Luzerner Kantonsspital

Lucerne, 6000, Switzerland

Location

Kantonsspital St. Gallen

Sankt Gallen, 9007, Switzerland

Location

Onkologiezentrum Thun-Berner Oberland

Thun, 3600, Switzerland

Location

Kantonsspital Winterthur

Winterthur, 8401, Switzerland

Location

Related Publications (5)

• 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.

  PMID: 17647245 BACKGROUND

• 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.

  PMID: 16149088 BACKGROUND

• 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.

  PMID: 15310773 BACKGROUND

• 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.

  PMID: 18725649 BACKGROUND

• 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.

  PMID: 29228091 DERIVED

MeSH Terms

Conditions

Neoplasm Metastasis; Neoplasms

Interventions

130-nm albumin-bound paclitaxel; Albumin-Bound Paclitaxel

Condition Hierarchy (Ancestors)

Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Heidi Roschitzki-Voser
• Organization: International Breast Cancer Study Group (IBCSG)

heidi.roschitzki@ibcsg.org

+41 31 511 94 18

Study Officials

• 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

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: November 28, 2012
• First Posted: December 10, 2012
• Study Start: April 1, 2013
• Primary Completion: May 1, 2016
• Study Completion: March 16, 2023
• Last Updated: June 1, 2023
• Results First Posted: March 27, 2020

Record last verified: 2023-05

Locations

IT (11); IE (10); SL (1); CH (11); ES (5); BE (3)