Study of Chemoembolisation Using Irinotecan Bead Prior to Surgery in Metastatic Colorectal Cancer (PARAGON-II)
Primary Purpose
Metastatic Colorectal Cancer
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Irinotecan Bead
Sponsored by
About this trial
This is an interventional treatment trial for Metastatic Colorectal Cancer
Eligibility Criteria
Inclusion criteria
- Presence of potentially resectable colorectal cancer liver metastases, with less than 60% liver tumour replacement. The consulting surgeon, according to local practice, will determine resectability.
- Patients having undergone complete resection of the primary tumour without gross or microscopic evidence of residual disease (R0), or the primary tumour is considered R0 resectable at screening.
- Age: 18-80 years.
- ECOG Status ≤2.
- No previous irinotecan-containing chemotherapy for advanced disease.
- Previous chemotherapy is allowed (unless it contained irinotecan), but must have ended at least one month prior to study entry.
- Presence of adequate contraception in fertile (M/F) patients. Pregnant or lactating women are excluded.
- Absence of any other previous malignancy other than adequately treated in situ carcinoma of the cervix or non-melanoma skin cancer (unless there has been a disease-free interval of at least 10 years).
- Patients should not have participated in another clinical trial with any investigational drug in the 30 days prior to enrolment.
Absence of:
- Peripheral neuropathy (CTC > grade 1)
- Uncontrolled congestive heart failure or angina pectoris, or hypertension or arrhythmia.
- History of significant neurologic or psychiatric disorders
- Active infection
- Written informed consent according to ICH/EU GCP, and any applicable local, national or international regulations.
- Patients with liver-dominant disease, defined as ≥80% of the tumour body burden confined to the liver. Unilobar disease, or bilobar disease suitable for treatment in a single chemoembolisation procedure, with a maximum of 4 lesions.
- Hematologic function: WBC ≥3.0 x 10*9/L, platelets ≥100 x 10*9/L, Absolute neutrophil count > 1.5 x 10*9/l.
Adequate organ function as measured by:
- Serum creatinine ≤2 x upper limit of normal (ULN).
- Serum transaminases (AST & ALT) ≤5 x ULN.
- Total bilirubin ≤1.5 x ULN.
- Prothrombin time >50% of normal.
Exclusion criteria
- Extrahepatic metastases constituting >20% of tumour body burden.
Contraindications to irinotecan:
- Chronic inflammatory bowel disease and/or bowel obstruction.
- History of severe hypersensitivity reactions to irinotecan hydrochloride trihydrate.
- Severe bone marrow failure.
- Concomitant use with St John's Wort.
- Active bacterial, viral or fungal infection within 72 hours of study entry.
- Allergy to contrast media that cannot be managed with standard care.
Any contraindication for hepatic embolisation procedures:
- porto-systemic shunt.
- hepatofugal blood flow.
- severe atheromatosis.
- Contraindication to hepatic artery catheterisation, such as a patient with severe peripheral vascular disease precluding catheterisation.
- Other significant medical or surgical condition, or any medication or treatment regimens, that would place the patient at undue risk, that would preclude the safe use of chemoembolisation or would interfere with study participation.
Sites / Locations
- Medical University Vienna, AKH
- Centre Hépato-Biliaire, Hôpital Paul Brousse
- Basingstoke and North Hampshire NHS Foundation Trust
- University Hospital Aintree
- North Manchester General Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
1
Arm Description
Irinotecan Bead
Outcomes
Primary Outcome Measures
Tumour resectability at surgery
Secondary Outcome Measures
Safety assessed by SAE and AE monitoring (NCI CTCAE v3.0)
Full Information
NCT ID
NCT00844233
First Posted
February 9, 2009
Last Updated
July 15, 2021
Sponsor
Boston Scientific Corporation
Collaborators
Biocompatibles UK Ltd
1. Study Identification
Unique Protocol Identification Number
NCT00844233
Brief Title
Study of Chemoembolisation Using Irinotecan Bead Prior to Surgery in Metastatic Colorectal Cancer
Acronym
PARAGON-II
Official Title
A Single Arm Phase II Study of Neoadjuvant Therapy Using Irinotecan Bead in Patients With Resectable Liver Metastases From Colorectal Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
July 2021
Overall Recruitment Status
Completed
Study Start Date
February 2009 (undefined)
Primary Completion Date
September 2011 (Actual)
Study Completion Date
October 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Boston Scientific Corporation
Collaborators
Biocompatibles UK Ltd
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The objective of this study is to evaluate the safety and efficacy of Irinotecan Bead in the neoadjuvant treatment (i.e. the Irinotecan Bead is administered prior to surgery) of resectable liver metastases from colorectal cancer.
Detailed Description
The Primary Endpoint of this study is Tumour resectability at surgery. Secondary Endpoints:
Safety assessed by SAE and AE monitoring (NCI CTCAE v3.0)
Tumour response assessed by imaging (RECIST and necrosis)
Viable residual tumour assessed by pathological evaluation of resected liver tissue.
Recurrence (time and site) following resection
Correlation of tumour response by imaging and pathology
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Colorectal Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
40 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Experimental
Arm Description
Irinotecan Bead
Intervention Type
Device
Intervention Name(s)
Irinotecan Bead
Other Intervention Name(s)
Irinotecan Bead, PARAGON Bead
Intervention Description
Irinotecan eluting bead
Primary Outcome Measure Information:
Title
Tumour resectability at surgery
Time Frame
1 month
Secondary Outcome Measure Information:
Title
Safety assessed by SAE and AE monitoring (NCI CTCAE v3.0)
Time Frame
1 month
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria
Presence of potentially resectable colorectal cancer liver metastases, with less than 60% liver tumour replacement. The consulting surgeon, according to local practice, will determine resectability.
Patients having undergone complete resection of the primary tumour without gross or microscopic evidence of residual disease (R0), or the primary tumour is considered R0 resectable at screening.
Age: 18-80 years.
ECOG Status ≤2.
No previous irinotecan-containing chemotherapy for advanced disease.
Previous chemotherapy is allowed (unless it contained irinotecan), but must have ended at least one month prior to study entry.
Presence of adequate contraception in fertile (M/F) patients. Pregnant or lactating women are excluded.
Absence of any other previous malignancy other than adequately treated in situ carcinoma of the cervix or non-melanoma skin cancer (unless there has been a disease-free interval of at least 10 years).
Patients should not have participated in another clinical trial with any investigational drug in the 30 days prior to enrolment.
Absence of:
Peripheral neuropathy (CTC > grade 1)
Uncontrolled congestive heart failure or angina pectoris, or hypertension or arrhythmia.
History of significant neurologic or psychiatric disorders
Active infection
Written informed consent according to ICH/EU GCP, and any applicable local, national or international regulations.
Patients with liver-dominant disease, defined as ≥80% of the tumour body burden confined to the liver. Unilobar disease, or bilobar disease suitable for treatment in a single chemoembolisation procedure, with a maximum of 4 lesions.
Hematologic function: WBC ≥3.0 x 10*9/L, platelets ≥100 x 10*9/L, Absolute neutrophil count > 1.5 x 10*9/l.
Adequate organ function as measured by:
Serum creatinine ≤2 x upper limit of normal (ULN).
Serum transaminases (AST & ALT) ≤5 x ULN.
Total bilirubin ≤1.5 x ULN.
Prothrombin time >50% of normal.
Exclusion criteria
Extrahepatic metastases constituting >20% of tumour body burden.
Contraindications to irinotecan:
Chronic inflammatory bowel disease and/or bowel obstruction.
History of severe hypersensitivity reactions to irinotecan hydrochloride trihydrate.
Severe bone marrow failure.
Concomitant use with St John's Wort.
Active bacterial, viral or fungal infection within 72 hours of study entry.
Allergy to contrast media that cannot be managed with standard care.
Any contraindication for hepatic embolisation procedures:
porto-systemic shunt.
hepatofugal blood flow.
severe atheromatosis.
Contraindication to hepatic artery catheterisation, such as a patient with severe peripheral vascular disease precluding catheterisation.
Other significant medical or surgical condition, or any medication or treatment regimens, that would place the patient at undue risk, that would preclude the safe use of chemoembolisation or would interfere with study participation.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Professor Graeme Poston, MB, MS, FRCS
Organizational Affiliation
Consultant General Surgeon
Official's Role
Principal Investigator
Facility Information:
Facility Name
Medical University Vienna, AKH
City
Vienna
ZIP/Postal Code
1090
Country
Austria
Facility Name
Centre Hépato-Biliaire, Hôpital Paul Brousse
City
Villejuif
ZIP/Postal Code
94804
Country
France
Facility Name
Basingstoke and North Hampshire NHS Foundation Trust
City
Basingstoke
ZIP/Postal Code
RG24 9NA
Country
United Kingdom
Facility Name
University Hospital Aintree
City
Liverpool
ZIP/Postal Code
L9 7AL
Country
United Kingdom
Facility Name
North Manchester General Hospital
City
Manchester
ZIP/Postal Code
M8 5RB
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
27561844
Citation
Jones RP, Malik HZ, Fenwick SW, Terlizzo M, O'Grady E, Stremitzer S, Gruenberger T, Rees M, Plant G, Figueras J, Albiol M, Adam R, Awad S, Poston GJ. PARAGON II - A single arm multicentre phase II study of neoadjuvant therapy using irinotecan bead in patients with resectable liver metastases from colorectal cancer. Eur J Surg Oncol. 2016 Dec;42(12):1866-1872. doi: 10.1016/j.ejso.2016.07.142. Epub 2016 Aug 10.
Results Reference
derived
PubMed Identifier
23216781
Citation
Jones RP, Dunne D, Sutton P, Malik HZ, Fenwick SW, Terlizzo M, O'Grady E, Koelblinger C, Stattner S, Stremitzer S, Gruenberger T, Poston GJ. Segmental and lobar administration of drug-eluting beads delivering irinotecan leads to tumour destruction: a case-control series. HPB (Oxford). 2013 Jan;15(1):71-7. doi: 10.1111/j.1477-2574.2012.00587.x. Epub 2012 Oct 16.
Results Reference
derived
Links:
URL
http://www.biocompatibles.com
Description
Sponsor company website
Learn more about this trial
Study of Chemoembolisation Using Irinotecan Bead Prior to Surgery in Metastatic Colorectal Cancer
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