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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 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: August 18, 2014
Last verified: August 2014
  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 Each of three arms will be compared to a historical reference of seven-month median progression-free survival (PFS) based on the most recent trial with docetaxel as control arm to determine whether any of the three arms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 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.
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 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.
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 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.
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01746225

  Show 41 Study Locations
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: August 18, 2014
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
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 22, 2014