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

NCT00124943 | Completed Phase 1 Results

• 1 other identifier: CVR003
• Study Type: interventional
• Target: 112
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Coronary Restenosis

Keywords

Prevention of Instent Restenosis

Outcome Measures

Primary Outcomes (5)

• Phase I: Number of Participants With Dose-limiting Toxicities

  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.

  Up to 1 week following percutaneous coronary intervention.

• Number of Participants With Procedural Complications

  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.

  From Day 0 - Day 1 (from study drug administration until 24 hours post-procedure).

• Number of Participants With Treatment Emergent Adverse Events (AEs)

  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.

  Up to 6 months.

• Number of Participants With Major Adverse Cardiac Events (MACE) at 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.

  From the day of Percutaneous Coronary Intervention to 1 Month.

• Number of Participants With Major Adverse Cardiac Events (MACE) at 6 Months

  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.

  From the day of Percutaneous Coronary Intervention to Month 6.

Secondary Outcomes (3)

• 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

Study Arms (4)

10 mg/m^2 nanoparticle paclitaxel

EXPERIMENTAL

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).

Drug: Nanoparticle Paclitaxel

22 mg/m^2 nanoparticle paclitaxel

EXPERIMENTAL

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).

Drug: Nanoparticle Paclitaxel

35 mg/m^2 nanoparticle paclitaxel

EXPERIMENTAL

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).

Drug: Nanoparticle Paclitaxel

45 mg/m^2 nanoparticle paclitaxel

EXPERIMENTAL

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).

Drug: Nanoparticle Paclitaxel

Interventions

Nanoparticle Paclitaxel DRUG

Nanoparticle albumin-bound paclitaxel, administered via intracoronary catheter.

Also known as: ABI-007, Abraxane®, Coroxane™

10 mg/m^2 nanoparticle paclitaxel; 22 mg/m^2 nanoparticle paclitaxel; 35 mg/m^2 nanoparticle paclitaxel; 45 mg/m^2 nanoparticle paclitaxel

Eligibility Criteria

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

You may qualify if:

• 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).
• By intravascular ultrasound (IVUS), stent is fully opposed and has a minimum diameter of 2.5 mm or an in-stent luminal area ≥ 5.0 mm\^2
• Patient or guardian has provided a signed written informed consent to participate in the study and in all follow-up assessments using a form that is approved by the local Institutional Review Board (IRB)/Ethics Committee of the investigative site.

You may not qualify if:

• 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.
• Patient has a life expectancy of less than 12 months or there are factors making clinical and/or angiographic follow-up difficult
• Any significant medical condition which, in the investigator's opinion, may interfere with the patient's optimal participation in the study
• Heart transplant candidate or recipient
• Patient is immunosuppressed or is HIV positive.
• Patient has experienced a Q wave or a non Q wave myocardial infarction (MI) with documented total creatine kinase (CK) ≥2 times normal within the preceding 24 hours and the CK and creatine kinase-MB fraction (CK-MB) enzymes remain above normal at the time of the procedure.

Sponsors & Collaborators

• Celgene Corporation: lead

MeSH Terms

Conditions

Coronary Restenosis

Interventions

Taxes; Albumin-Bound Paclitaxel

Condition Hierarchy (Ancestors)

Coronary Stenosis; Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Economics; Health Care Economics and Organizations; 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: Associate Director, Clinical Trials Disclosure
• Organization: Celgene Corporation

clinicaltrialdisclosure@celgene.com

1-888-260-1599

Study Officials

• Jose' Iglesias, MD

  Celgene Corporation

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 27, 2005
• First Posted: July 29, 2005
• Study Start: July 1, 2005
• Primary Completion: August 1, 2009
• Study Completion: August 1, 2009
• Last Updated: April 2, 2012
• Results First Posted: March 8, 2012

Record last verified: 2012-03