Clinical Trial: Use of Nanoparticle Paclitaxel (ABI-007) for the Prevention of In-Stent Restenosis

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase I/II Safety Trial of Intracoronary Administration of Systemic Nanoparticle Paclitaxel (ABI-007) for the Prevention of In-Stent Restenosis

Brief Summary: The purpose of this study was to investigate the use of systemic intracoronary administration of albumin-bound paclitaxel, ABI-007, for the prevention and reduction of restenosis following de novo stenting or following angioplasty for in-stent restenosis.

Detailed Summary: This study consisted of a Phase I non-randomized dose escalation phase to determine the maximum tolerated dose and a randomized Phase II component to assess preliminary efficacy. Nanoparticle paclitaxel was administered by intracoronary catheter following either successful and uncomplicated stenting of de novo lesions in native coronary arteries or following successful and uncomplicated balloon angioplasty of instent restenosis (ISR) lesions.
Sponsor: Celgene Corporation

Current Primary Outcome:

  • Phase I: Number of Participants With Dose-limiting Toxicities [ Time Frame: Up to 1 week following percutaneous coronary intervention. ]

    Toxicities were evaluated based on the U.S. National Cancer Institute (NCI) Common Terminology Criteria (CTC) for Adverse Events version 3.0. Any drug-related toxicities considered CTC Grade 3 or 4 were considered dose limiting.

    The maximum tolerated dose was defined as the lesser of 45 mg/m^2 or the dose at which any drug related toxicities were observed.

  • Number of Participants With Procedural Complications [ Time Frame: From Day 0 - Day 1 (from study drug administration until 24 hours post-procedure). ]

    Procedural complications include the following:

    1. Haemodynamic monitoring: changes in heart rate, arterial blood pressure or electrocardiogram changes;
    2. Arrhythmia: premature ventricular complexes, brady or tachyarrhythmia;
    3. Allergic reactions: rash, flushing, pyrexia, urticaria, angio-oedema;
    4. Angiographic complications: coronary artery spasm, dissection, thrombosis, TIMI (Thrombolysis In Myocardial Infarction) flow, no reflow;
    5. Clinical changes: chest pain.
  • Number of Participants With Treatment Emergent Adverse Events (AEs) [ Time Frame: Up to 6 months. ]

    An AE is any unfavorabl

    Original Primary Outcome:

    • The primary objective of the study is to determine the feasibility of intracoronary administration, and to determine a safe and appropriate intracoronary dose for
    • future clinical trials of ABI-007 administered to patients after successful PTCA and stenting of de novo lesions or angioplasty of ISR lesions, and to evaluate the
    • incidence of treatment-emergent adverse events and serious adverse events.


    Current Secondary Outcome:

    • Percentage of Participants With Binary Restenosis [ Time Frame: 6 months ]
      Binary restenosis was assessed by quantitative coronary angiography and defined as >50% diameter stenosis within the stented region (In-stent) or the stented region plus 5 mm on either side of the stent (In-segment) at follow-up. Angiograms were centrally assessed by the Angiographic Core Laboratory.
    • Late Lumen Loss [ Time Frame: Day 0 (post-procedure baseline) and 6 months. ]

      Late lumen loss represents the extent of neointimal hyperplasia within the stented region (In-stent) or the stented region plus 5 mm on either side of the stent (In-segment) and was measured by quantitative coronary angiography.

      Late Loss = Minimum Lumen Diameter (MLD) Post Procedure minus the MLD at Follow-up.

    • Percentage of In-Stent Volume Obstruction at 6 Months [ Time Frame: 6 months ]
      In-stent volume obstruction at 6 months was measured by intra-vascular ultrasound (IVUS) and centrally assessed by the IVUS Core Laboratory. Percent in-stent volume obstruction was calculated as neointimal volume / stent volume * 100.


    Original Secondary Outcome: Secondary objectives of the study are to determine the rate of restenosis at 6 months for the dose that will be used for future intracoronary ABI-007 trials.

    Information By: Celgene

    Dates:
    Date Received: July 27, 2005
    Date Started: July 2005
    Date Completion:
    Last Updated: March 28, 2012
    Last Verified: March 2012