A Phase I/II Safety Trial of Intracoronary Administration of Systemic Nanoparticle Paclitaxel (ABI-007) for the Prevention of In-Stent Restenosis
Overview
- Phase
- Phase 1
- Intervention
- Nanoparticle Paclitaxel
- Conditions
- Coronary Restenosis
- Sponsor
- Celgene Corporation
- Enrollment
- 112
- Primary Endpoint
- Phase I: Number of Participants With Dose-limiting Toxicities
- Status
- Completed
- Last Updated
- 14 years ago
Overview
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 Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male or non-pregnant and non-lactating female, and ≥ 18 years of age.
- •Diagnosis of angina pectoris or unstable angina pectoris or patients with documented silent ischemia.
- •Left ventricular ejection fraction ≥30%
- •Patient has undergone successful and uncomplicated stenting of up to 2 de novo lesions in native coronary arteries OR patient has undergone successful and uncomplicated balloon angioplasty of up to 2 in-stent restenosis (ISR) lesions in native coronary arteries, but not both.
- •Thrombolysis In Myocardial Infarction (TIMI) 3 coronary flow post-stenting for de novo lesions or post balloon angioplasty for ISR lesions.
- •No angiographic evidence of thrombus post-procedure.
- •Target vessel ≥2.5 mm diameter (by angiography).
- •Each de novo lesion is such that it is stented with ≤ 25 mm of single continuous stent.
- •Each in-stent restenosis (ISR) lesion is ≤ 25 mm in length.
- •There is at least 5 mm of non-diseased vessel on either side of target lesion(s).
Exclusion Criteria
- •Target de novo lesion was treated with a drug-eluting stent
- •Target ISR lesion requires any treatment other than balloon angioplasty
- •Patient has both a de novo lesion and an ISR lesion.
- •If more than 2 lesions are treated with percutaneous coronary intervention (PCI), or it is anticipated that additional lesions will require treatment within 2 months.
- •Previous PCI within preceding two months.
- •Intended surgical intervention within 6 months of enrollment in the study.
- •Unprotected left main disease with \>50% stenosis
- •Malapposition, dissection, or unmasking of a significant narrowing in the inflow or outflow area of the implanted stent.
- •Women who are pregnant and women of child bearing potential who do not use adequate contraception
- •Previous participation in another study with any investigational drug or device within the past 30 days or current enrollment in any other clinical protocol or investigational drug or device trial.
Arms & Interventions
10 mg/m^2 nanoparticle paclitaxel
Participants received a single dose of 10 mg/m\^2 nanoparticle paclitaxel administered via intracoronary catheter immediately following percutaneous transluminal coronary angioplasty/stenting (de novo lesion) or balloon angioplasty (in-stent restenosis lesions).
Intervention: Nanoparticle Paclitaxel
22 mg/m^2 nanoparticle paclitaxel
Participants received a single dose of 22 mg/m\^2 nanoparticle paclitaxel administered via intracoronary catheter immediately following percutaneous transluminal coronary angioplasty/stenting (de novo lesions) or balloon angioplasty (in-stent restenosis lesions).
Intervention: Nanoparticle Paclitaxel
35 mg/m^2 nanoparticle paclitaxel
Participants received a single dose of 35 mg/m\^2 nanoparticle paclitaxel administered via intracoronary catheter immediately following percutaneous transluminal coronary angioplasty/stenting (de novo lesions) or balloon angioplasty (in-stent restenosis lesions).
Intervention: Nanoparticle Paclitaxel
45 mg/m^2 nanoparticle paclitaxel
Participants received a single dose of 45 mg/m\^2 nanoparticle paclitaxel administered via intracoronary catheter immediately following percutaneous transluminal coronary angioplasty/stenting (de novo lesions) or balloon angioplasty (in-stent restenosis lesions).
Intervention: Nanoparticle Paclitaxel
Outcomes
Primary Outcomes
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 Treatment Emergent Adverse Events (AEs)
Time Frame: Up to 6 months.
An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product. An SAE is any event that: * is fatal or life threatening * results in persistent or significant disability or or incapacity; * requires or prolongs existing hospitalization; * is a congenital anomaly/birth defect in the offspring of a patient who received medication; * conditions not included above that may jeopardize the patient or require intervention to prevent one of the outcomes listed above.
Number of Participants With Major Adverse Cardiac Events (MACE) at 1 Month
Time Frame: From the day of Percutaneous Coronary Intervention to 1 Month.
Major Adverse Cardiac Events (MACE) includes cardiac death, Coronary Artery Bypass Surgery, Myocardial Infarction, Target Vessel Revascularization (TVR) or Target Lesion Revascularization (TLR) and stent/vessel thrombotic occlusion.
Number of Participants With Major Adverse Cardiac Events (MACE) at 6 Months
Time Frame: From the day of Percutaneous Coronary Intervention to Month 6.
Major Adverse Cardiac Events (MACE) includes cardiac death, Coronary Artery Bypass Surgery, Myocardial Infarction, Target Vessel Revascularization (TVR) or Target Lesion Revascularization (TLR) and stent/vessel thrombotic occlusion.
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.
Secondary Outcomes
- Percentage of Participants With Binary Restenosis(6 months)
- Late Lumen Loss(Day 0 (post-procedure baseline) and 6 months.)
- Percentage of In-Stent Volume Obstruction at 6 Months(6 months)