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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02229864




Registration number
NCT02229864
Ethics application status
Date submitted
9/06/2014
Date registered
3/09/2014
Date last updated
12/03/2021

Titles & IDs
Public title
Pharmacokinetics of Everolimus in Absorb BVS in Patients With Coronary Artery Lesions
Scientific title
ABSORB III RCT Pharmacokinetics (PK) Sub-study
Secondary ID [1] 0 0
10-392 B
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Coronary Artery Disease 0 0
Coronary Artery Stenosis 0 0
Coronary Disease 0 0
Coronary Stenosis 0 0
Diffuse Intrinsic Pontine Glioma 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Coronary heart disease
Cardiovascular 0 0 0 0
Other cardiovascular diseases
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)
Cancer 0 0 0 0
Brain

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Late MRI and PET/CT 6 weeks post chemo/RT
Treatment: Devices - Coronary artery stenting: Absorb BVS

Experimental: Coronary artery stenting: Absorb BVS - Subjects receiving Absorb Bioresorbable Vascular Scaffold (BVS)

Experimental: R1: erlotinib versus dasatinib - EGFR+ only Tarceva® (erlotinib): 25 mg and 100 mg tablets. The prescribed dose is 125 mg/m²/day orally, once daily. Sprycel® (dasatinib): 20 mg and 50 mg tablets. The prescribed dose is 85 mg/m²/dose, orally, twice daily, i.e. 170 mg/m2/day.

Experimental: R2: everolimus versus dasatinib - PTEN-loss only Votubia® (everolimus): 2.5 mg tablets. The prescribed dose is 5 mg/m²/day, orally, once daily. Sprycel® (dasatinib): 20 mg and 50 mg tablets. The prescribed dose is 85 mg/m²/dose, orally, twice daily, i.e. 170 mg/m2/day.

Experimental: R3: erlotinib versus everolimus versus dasatinib - EGFR+ and PTEN-loss or inconclusive biopsy Tarceva® (erlotinib): 25 mg and 100 mg tablets. The prescribed dose is 125 mg/m²/day orally, once daily. Votubia® (everolimus): 2.5 mg tablets. The prescribed dose is 5 mg/m²/day, orally, once daily. Sprycel® (dasatinib): 20 mg and 50 mg tablets. The prescribed dose is 85 mg/m²/dose, orally, twice daily, i.e. 170 mg/m2/day.

Experimental: Cohort Dasatinib - Neither EGFR overexpression nor loss of PTEN expression Sprycel® (dasatinib): 20 mg and 50 mg tablets. The prescribed dose is 85 mg/m²/dose, orally, twice daily, i.e. 170 mg/m2/day


Other interventions: Late MRI and PET/CT 6 weeks post chemo/RT
Patients will have late a MRI and PET/CT 6 weeks post chemo/RT. A whole body PET/CT will look at parameters: SUVmaxm PERCIST, RECIST 1.1, ?SUV (PET1-2), ?SUV (early -late), Glycolytic tumour volume (GTV). MRI T2 (1-3mm slice as per NS Radiology protocol and ESGAR guideline) will look at parameters: DWI \& ADC value (preferably on a single camera with reproducible ADC value), Local Staging, MRF involvement, EMVI, nodal status, MR volumetry, and desmoplastic reaction.

Treatment: Devices: Coronary artery stenting: Absorb BVS
* Scaffold diameters: 2.5, 3.0 and 3.5 mm
* Scaffold lengths: 8, 12, 18, and 28 mm
Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Devices
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Maximum Concentration (Cmax)
Timepoint [1] 0 0
0 to 30 days
Primary outcome [2] 0 0
Time of Maximum (Tmax)
Timepoint [2] 0 0
0 to 30 days
Primary outcome [3] 0 0
AUC24h
Timepoint [3] 0 0
0 to 24 hours
Primary outcome [4] 0 0
AUC Last
Timepoint [4] 0 0
0 to 30 days
Primary outcome [5] 0 0
AUC 0-infinity
Timepoint [5] 0 0
0 to 30 days
Primary outcome [6] 0 0
Terminal Elimination Rate Constant (?z)
Timepoint [6] 0 0
0 to 30 days
Primary outcome [7] 0 0
Terminal Elimination Half-life (t1/2term)
Timepoint [7] 0 0
0 to 30 days
Primary outcome [8] 0 0
Drug Clearance (CL)
Timepoint [8] 0 0
0 to 30 days
Primary outcome [9] 0 0
Predictive value of PET/CT and MRI 2 weeks into chemo-irradiation for developing a pathologic complete response at surgery.
Timepoint [9] 0 0
2 years
Primary outcome [10] 0 0
Overall Survival
Timepoint [10] 0 0
Assessed up two years after randomization
Secondary outcome [1] 0 0
Number of Participants With Target Lesion Failure (TLF)
Timepoint [1] 0 0
0 to 1853 Days
Secondary outcome [2] 0 0
Number of Participants With All Death
Timepoint [2] 0 0
0 to 1853 Days
Secondary outcome [3] 0 0
Number of Participants With All Myocardial Infarction (MI)
Timepoint [3] 0 0
0 to 1853 Days
Secondary outcome [4] 0 0
Number of Participants With All Target Lesion Revascularization (TLR)
Timepoint [4] 0 0
0 to 1853 Days
Secondary outcome [5] 0 0
Number of Participants With All Target Vessel Revascularization (TVR)
Timepoint [5] 0 0
0 to 1853 Days
Secondary outcome [6] 0 0
Number of Participants With All Revascularization
Timepoint [6] 0 0
0 to 1853 Days
Secondary outcome [7] 0 0
Number of Participants With Acute Stent/Scaffold Thrombosis (Definite/Probable)
Timepoint [7] 0 0
= 1 day
Secondary outcome [8] 0 0
Number of Participants With Subacute Stent/Scaffold Thrombosis (Definite/Probable)
Timepoint [8] 0 0
>1 to 30 days
Secondary outcome [9] 0 0
Number of Participants With Late Stent/Scaffold Thrombosis (Definite/Probable)
Timepoint [9] 0 0
31 to 393 days
Secondary outcome [10] 0 0
Number of Participants With Cumulative Stent/Scaffold Thrombosis (Definite/Probable)
Timepoint [10] 0 0
0 to 1853 Days
Secondary outcome [11] 0 0
Feasibility of conducting additional PET and MRI scans at 6 weeks post-treatment.
Timepoint [11] 0 0
2 years
Secondary outcome [12] 0 0
Utility of adding PET scan to the baseline staging of patients
Timepoint [12] 0 0
2 years
Secondary outcome [13] 0 0
Pathologic response according to Tumour Regression Grade (TRG)
Timepoint [13] 0 0
2.5 years
Secondary outcome [14] 0 0
Impact of pCR rates on long term disease control
Timepoint [14] 0 0
5 years

Eligibility
Key inclusion criteria
General

1. 18 years of age.
2. Subject or a legally authorized representative must provide written Informed Consent prior to any study related procedure, per site requirements.
3. Evidence of myocardial. In the absence of noninvasive ischemia, FFR must be done and indicative of ischemia.
4. An acceptable candidate for coronary artery bypass graft (CABG) surgery.
5. Female subject of childbearing potential who does not plan pregnancy for up to 1 year following the index procedure.
6. Female subject is not breast-feeding at the time of the screening visit and will not be breast-feeding for up to 1 year following the index procedure.
7. Subject agrees to not participate in any other investigational or invasive clinical study for a period of 1 year following the index procedure.

Angiographic

1. One or two de novo target lesions:

1. If two target lesions are present, they must be present in different epicardial vessels and both must satisfy the angiographic eligibility criteria.
2. The definition of epicardial vessels means the left anterior descending (LAD), left coronary artery (LCX), and right coronary artery (RCA) and their branches. Thus, the patient must not have lesions requiring treatment in e.g. both the LAD and a diagonal branch.
2. Target lesion(s) must be located in a native coronary artery with a visually estimated or quantitatively assessed % diameter stenosis (DS) of = 50% and < 100% with a thrombolysis in myocardial infarction (TIMI) flow of = 1 and one of the following: stenosis = 70%, an abnormal functional test (e.g., fractional flow reserve (FFR), stress test), unstable angina or post-infarct angina.

1. Lesion(s) must be located in a native coronary artery with reference vessel diameter (RVD) by visual estimation of = 2.50 mm and = 3.75 mm.
2. Lesion(s) must be located in a native coronary artery with length by visual estimation of = 24 mm.

General
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Any surgery requiring general anesthesia or discontinuation of aspirin and/or an Adenosine diphosphate receptor (ADP) antagonist is planned within 12 months after the procedure.
2. Subject has known hypersensitivity or contraindication to device material and its degradants (everolimus, poly (L-lactide), poly (DL-lactide), lactide, lactic acid) and cobalt, chromium, nickel, platinum, tungsten, acrylic and fluoro polymers that cannot be adequately pre-medicated. Subject has a known contrast sensitivity that cannot be adequately pre-medicated.
3. Subject has known allergic reaction, hypersensitivity or contraindication to aspirin; or to clopidogrel and prasugrel and ticagrelor; or to heparin and bivalirudin, and therefore cannot be adequately treated with study medications.
4. Subject had an acute myocardial infarction (AMI: STEMI or NSTEMI) within 72 hours of the index procedure and both creatine kinase (CK) and creatine kinase myocardial-band isoenzyme (CK-MB) have not returned to within normal limits at the time of index procedure; or subject with stable angina or silent ischemia has CK-MB that is greater than normal limits at the time of the index procedure.
5. Subject is currently experiencing clinical symptoms consistent with new onset AMI (STEMI or NSTEMI), such as nitrate-unresponsive prolonged chest pain with ischemic ECG changes.
6. Subject has a cardiac arrhythmia as identified at the time of screening for which at least one of the following criteria is met:

1. Subject requires coumadin or any other agent for chronic oral anticoagulation
2. Subject is likely to become hemodynamically unstable due to their arrhythmia
3. Subject has poor survival prognosis due to their arrhythmia
7. Subject has a left ventricular ejection fraction (LVEF) < 30%
8. Subject has undergone prior percutaneous coronary intervention (PCI) within the target vessel(s) during the last 12 months.
9. Subject requires future staged PCI either in target or non-target vessels or subject requires future peripheral interventions < 30 days after the index procedure.
10. Subject has received any solid organ transplants or is on a waiting list for any solid organ transplants.
11. At the time of screening, the subject has a malignancy that is not in remission.
12. Subject is receiving immunosuppressant therapy or has known immunosuppressive or severe autoimmune disease that requires chronic immunosuppressive therapy (e.g., human immunodeficiency virus, systemic lupus erythematosus, etc.). Note: corticosteroids are not included as immunosuppressant therapy.
13. Subject has previously received or is scheduled to receive radiotherapy to a coronary artery (vascular brachytherapy), or the chest/mediastinum.
14. Subject is receiving or will require chronic anticoagulation therapy (e.g., coumadin, dabigatran, apixaban, rivaroxaban or any other agent for any reason).
15. Subject has a platelet count < 100,000 cells/mm3 or > 700,000 cells/mm3.
16. Subject has a documented or suspected hepatic disorder as defined as cirrhosis or Child-Pugh = Class B.
17. Subject has renal insufficiency as defined as an estimated glomerular filtration rate (GFR) < 30 ml/min/1.73m2 or dialysis at the time of screening.
18. Subject is high risk of bleeding for any reason; has a history of bleeding diathesis or coagulopathy; has had a significant gastro-intestinal or significant urinary bleed within the past six months.
19. Subject has had a cerebrovascular accident or transient ischemic neurological attack (TIA) within the past six months, or any prior intracranial bleed, or any permanent neurologic defect, or any known intracranial pathology (e.g., aneurysm, arteriovenous malformation, etc.).
20. Subject has extensive peripheral vascular disease that precludes safe 6 French sheath insertion. Note: femoral arterial disease does not exclude the patient if radial access may be used.
21. Subject has life expectancy < 5 years for any non-cardiac cause or cardiac cause.
22. Subject is in the opinion of the Investigator or designee, unable to comply with the requirements of the study protocol or is unsuitable for the study for any reason.
23. Subject is currently participating in another clinical trial that has not yet completed its primary endpoint.
24. Subject is part of a vulnerable population

Angiographic

All exclusion criteria apply to the target lesion(s) or target vessel(s).

1. Lesion which prevents successful balloon pre-dilatation
2. Lesion is located in left main.
3. Aorto-ostial RCA lesion.
4. Lesion located within 3 mm of the origin of the LAD or LCX.
5. Lesion involving a bifurcation with a:

1. side branch = 2 mm in diameter, or
2. side branch with either an ostial or non-ostial lesion with diameter stenosis > 50%, or
3. side branch requiring dilatation.
6. Anatomy proximal to or within the lesion that may impair delivery of the Absorb BVS.
7. Vessel contains thrombus as indicated in the angiographic images or by intravascular ultrasound (IVUS) or optical coherence tomography (OCT).
8. Lesion or vessel involves a myocardial bridge.
9. Vessel has been previously treated with a stent at any time prior to the index procedure such that the Absorb BVS would need to cross the stent to reach the target lesion.
10. Vessel has been previously treated and the target lesion is within 5 mm proximal or distal to a previously treated lesion.
11. Target lesion located within an arterial or saphenous vein graft or distal to any arterial or saphenous vein graft.

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not applicable
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/05/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/10/2019
Sample size
Target
Accrual to date
Final
12
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Northern Sydney Cancer Centre, Royal North Shore Hospital - St Leonards
Recruitment postcode(s) [1] 0 0
2065 - St Leonards
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Michigan
Country [3] 0 0
France
State/province [3] 0 0
Val De Marne

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Abbott Medical Devices
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Innovative Therapies For Children with Cancer Consortium
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The ABSORB III PK sub-study is a prospective, open-label, non-blinded study enrolling approximately 12 subjects in up to 5 US sites. ABSORB III PK sub-study is a part of ABSORB III RCT (NCT01751906). The objective is to determine the pharmacokinetics of everolimus delivered by the Absorb BVS in a separate and non-randomized cohort of subjects who only receive Absorb BVS with a maximum of two de novo native coronary artery lesions after implantation of the Absorb BVS.

Note: The ABSORB III PK subjects will not contribute to the determination of the ABSORB III RCT primary endpoint.
Trial website
https://clinicaltrials.gov/study/NCT02229864
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
David G. Rizik, MD
Address 0 0
Scottsdale Healthcare, Scottsdale, AZ
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT02229864