- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00816777
Chemoembolization, Irinotecan Bead, Second Line Chemotherapy Treatment of Unresectable Metastatic Colorectal Cancer (PARAGON)
Feasibility and Prospective Randomized Study of Transarterial Chemoembolization Using Irinotecan Bead in Combination With Second Line Chemotherapy in the Treatment of Patients With Unresectable Metastatic Colorectal Cancer
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
There are many treatments for metastatic colorectal cancer to the liver, and both the application and outcomes are highly dependant on the patients disposition. Whilst resection results in the best long term survival, it is often not a viable treatment option.
Irinotecan Bead is an embolization device intended to treat colorectal cancer metastases of the liver. As an adjunct to this, irinotecan is present in the microspheres which is released in a controlled manner into the local environment of the tumor. Irinotecan Bead is a combination of an approved embolization device and an approved chemotherapy agent. The device is a PVA based embolization agent from Biocompatibles UK Ltd, and the irinotecan is sourced from an FDA approved supplier.
Irinotecan, a topoisomerase inhibitor, was the first systemic chemotherapy drug other than 5-Fluorouracil (5-FU) to demonstrate significant activity in the treatment of metastatic colorectal cancer. Irinotecan is approved for use in combination with 5-FU/folinic acid in patients without prior chemotherapy, and for the second-line treatment of metastatic colorectal cancer as a single agent in patients who have failed an established 5-FU containing treatment regimen.
The purpose of this combination device as a treatment for cancer in the liver is twofold:
(i) Nutrient and oxygen starvation of the tumor. (ii) Minimization of chemotherapy wash-out with prolonged contact with tumor tissue.
Irinotecan Bead can be administered intra-arterially in the same manner as conventional TACE. The benefit of this product is that TACE is achieved in a simpler one-step procedure by precisely embolizing the arteries feeding the tumor, and as an ancillary action, the Irinotecan Bead may release a controlled dose of irinotecan into the tumor bed.
The potential benefits of Irinotecan Bead could be significant since a sustainable release of chemotherapy over time could have a greater effect on tumor mass, because optimal therapeutic efficacy of Irinotecan (an S phase-specific cytotoxic drug) generally requires prolonged exposure of the tumor to concentrations exceeding a minimum threshold.
Studies of low-dose, protracted administration of Irinotecan and other camptothecin analogues in mice bearing xenografts of human tumors have shown less toxicity and equal to or better antitumor activity than shorter, more intense dosing schedules. With the proposed device, the in-vivo and pre-clinical data shows that there is reduced systemic levels of Irinotecan, when delivered to tumorous tissue following embolization, and a longer, sustained concentration of the active metabolite, SN-38.
This is a multicentre, open labeled, prospective, randomized, controlled phase II study designed to assess the clinical performance of chemoembolization with Irinotecan Bead in combination with intravenous chemotherapy (irinotecan monotherapy) versus intravenous chemotherapy alone in the treatment of unresectable liver metastases in patients with colorectal cancer who previously failed first line chemotherapy.
The primary endpoint will be Progression Free Survival measured from the first treatment in this study until progression. Additional endpoints will be Pharmacokinetics of systemic Irinotecan and SN-38 (Irinotecan Bead treatment for feasibility group only); Tumor Response measured according to RECIST; Local tumor response (extent of necrosis in the treated lesions); hepatic progression free survival measured from first treatment until progression in the liver; change in tumor markers (CEA and optional CA19-9); performance status and overall survival assessed by telephone follow-up. Safety will be measured by assessing Adverse Events and Toxicity according to the NCI CTCAE v3.0 criteria.
Approximately 70 patients will be enrolled. The first 10 patients will be enrolled in a feasibility safety evaluation in the test arm of the trial.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
Colorado
-
Aurora, Colorado, United States, 80045
- University of Colorado Cancer Center
-
-
Illinois
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Chicago, Illinois, United States, 60611
- Northwestern University
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Massachusetts
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Burlington, Massachusetts, United States, 01805
- Lahey Clinic
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Patients with confirmed diagnosis of stage IV colorectal cancer with unresectable liver metastases (primary tumor may be present)
- Patients with at least one measurable liver metastases, with size > 1cm (RECIST criteria)
- Patients with liver dominant disease defined as ≥50% tumor body burden confined to the liver
- Patients with patent main portal vein
- Performance status ≤ 2 ECOG
- Life expectancy > 6 months
- Aged ≥18 years
- Patient has failed (discontinued for progression or toxicity) one prior line of chemotherapy for metastatic disease, preferably oxaliplatin-based (e.g. FOLFOX, CAPOX). Note that substitutions of oral versus IV 5-FU formulations, changes in 5-FU schedules, or discontinuations/re-starting of the same chemotherapy drugs will not be considered as separate lines of therapy, nor will the addition of "biologics" such as bevacizumab, cetuximab, or panitumumab
- Patient has no previous treatment with irinotecan
- At least 4 weeks since last administration of last chemotherapy and /or radiotherapy
- Hematologic function: ANC ≥ 1.5 x 109/L, platelets ≥75 x10-9/L, INR <1.5 (patients on therapeutic anticoagulants are not eligible)
- Adequate liver function as measured by: Total bilirubin ≤ 2.0mg/dl, ALT, AST ≤5 times ULN, albumin ≥2.5g/dl,
- Adequate renal function (creatinine ≤ 2.0mg/dl)
- Women of child bearing potential and fertile men are required to use effective contraception (negative serum βHCG/urine test for women of child-bearing age)
- Signed, written informed consent
Exclusion Criteria:
- Patient eligible for curative treatment (i.e. resection or radiofrequency ablation). Note: resectability is defined as a single tumor <5cm with adequate liver function defined: Total bilirubin ≤ 2.0mg/dl, ALT, AST ≤5 times ULN, albumin ≥2.5g/dl
- Contraindications to irinotecan:
- Chronic inflammatory bowel disease and/or bowel obstruction
- History of severe hypersensitivity reactions to irinotecan hydrochloride trihydrate, lactic acid or to any of the excipients of Camptosar
- Severe bone marrow failure
- History of Gilbert Syndrome (specific testing not required)
- Concomitant use with St John's Wort (Hypericum)
- Active bacterial, viral or fungal infection within 72 hours of study entry
- Women who are pregnant or breast feeding
- Previous irinotecan based therapy for metastatic disease
- Patients' whose only measurable disease is within an area of the liver previously subject to radiotherapy
- Allergy to contrast media that cannot be managed with standard care (e.g. steroids)
- Presence of another malignancy with the exception of cervical carcinoma in situ and stage I basal or squamous carcinoma of the skin
- Contraindicated for MRI or CT
- Patients previously treated with transarterial embolization (with or without chemotherapy)
- Any contraindication for hepatic embolization procedures:
- Large shunt as determined by the investigator (pretesting with TcMMA not required)
- Severe atheromatosis
- Hepatofugal blood flow
- Main portal vein occlusion (e.g. thrombus or tumor)
- Other significant medical or surgical condition, or any medication or treatment, that would place the patient at undue risk, that would preclude the safe use of chemoembolization or would interfere with study participation
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Chemoembolization
Chemoembolization with Irinotecan Bead in combination with Intravenous Chemotherapy Group (test arm)
|
Intra arterial chemoembolization using Irinotecan Bead 100mg irinotecan per procedure in combination with irinotecan monotherapy 250mg/m2 alternating on a 3 weekly schedule
Other Names:
Irinotecan monotherapy: 250mg/m2 repeated every 3 weeks
Other Names:
|
ACTIVE_COMPARATOR: Chemotherapy
Irinotecan monotherapy: 250mg/m2 repeated every 3 weeks
|
Irinotecan monotherapy: 250mg/m2 repeated every 3 weeks
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Progression Free Survival
Time Frame: 1 year
|
1 year
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Survival
Time Frame: 1 year
|
1 year
|
|
Toxicity, Adverse Events and Serious Adverse Events (NCI CTCAE v3.0)
Time Frame: 6 weeks
|
0 - No data collected
|
6 weeks
|
Tumor Response (RECIST)
Time Frame: 1 year
|
1 year
|
|
Local Tumor Response (Extent of Necrosis in the Treated Lesions)
Time Frame: 1 year
|
1 year
|
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Hepatic Progression Free Survival
Time Frame: 1 year
|
Data not collected - study terminated ealry
|
1 year
|
Change in Tumor Marker
Time Frame: 1 year
|
1 year
|
|
Performance Status (ECOG)
Time Frame: 1 year
|
No data collected
|
1 year
|
Collaborators and Investigators
Sponsor
Collaborators
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms
- Neoplasms by Site
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Colonic Diseases
- Intestinal Diseases
- Intestinal Neoplasms
- Rectal Diseases
- Colorectal Neoplasms
- Rectal Neoplasms
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Topoisomerase Inhibitors
- Topoisomerase I Inhibitors
- Irinotecan
Other Study ID Numbers
- CA1013
- IDE G070122 (OTHER: FDA IDE)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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