Unresectable Metastatic Colo-rectal CancerPhase 1/2PARAGONNCT00816777
Chemoembolization, Irinotecan Bead, Second Line Chemotherapy Treatment of Unresectable Metastatic Colorectal Cancer
A Phase 1/2 study testing Chemoembolization with irinotecan Bead and Irinotecan in people with Unresectable Metastatic Colo-rectal Cancer, run by Generic Devices Consulting, Inc. at 3 sites in United States.
Trial summary
The primary objective of this study is to evaluate the safety and efficacy of Irinotecan Bead in combination with intravenous chemotherapy versus intravenous chemotherapy alone in the treatment of unresectable liver metastases in patients with colorectal cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Unresectable Metastatic Colo-rectal Cancer
- What is being tested?
- Chemoembolization with irinotecan Bead and Irinotecan
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 3 sitesUnited States
- Study dates
- Dec 2008to Mar 2011
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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)
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- 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
Trial locations and contacts
3 sites in 1 country.
United States3 sites
University of Colorado Cancer Center
Aurora, Colorado, 80045
Lahey Clinic
Burlington, Massachusetts, 01805
Northwestern University
Chicago, Illinois, 60611
About this study
Official title: 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
The primary objective of this study is to evaluate the safety and efficacy of Irinotecan Bead in combination with intravenous chemotherapy versus intravenous chemotherapy alone in the treatment of unresectable liver metastases in patients with colorectal cancer. The results of this study are intended to be used in support of a PMA application for a combination device
Read the 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.
- Being tested
- Chemoembolization with irinotecan Bead, Irinotecan
- Keywords
- Cancer, Carcinoma, Colon Cancer, Colorectal Cancer, Gastric Cancer, Gastrointestinal Cancer, Metastases, Metastatic Cancer, Metastatic Colorectal Cancer, Oncology, Rectal Cancer
- Medical subject headings
- Neoplasms, Carcinoma, Colonic Neoplasms, Colorectal Neoplasms, Stomach Neoplasms, Gastrointestinal Neoplasms, Neoplasm Metastasis, Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Chemoembolization with irinotecan BeadProcedure or surgery
Also called Trans arterial Chemoembolization, Irinotecan Bead
Intra arterial chemoembolization using Irinotecan Bead 100mg irinotecan per procedure in combination with irinotecan monotherapy 250mg/m2 alternating on a 3 weekly schedule
IrinotecanDrug
Also called camptosar
Irinotecan monotherapy: 250mg/m2 repeated every 3 weeks
| Study group | Role | What they receive |
|---|---|---|
| Chemoembolization | Experimental | Chemoembolization with Irinotecan Bead in combination with Intravenous Chemotherapy Group (test arm) Receives: Procedure: Chemoembolization with irinotecan Bead; Drug: Irinotecan |
| Chemotherapy | Active comparator | Irinotecan monotherapy: 250mg/m2 repeated every 3 weeks Receives: Drug: Irinotecan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression Free Survival
Measured: 1 year
Secondary outcomes (7)
Toxicity, Adverse Events and Serious Adverse Events (NCI CTCAE v3.0)
0 - No data collected
Measured: 6 weeks
Tumor Response (RECIST)
Measured: 1 year
Local Tumor Response (Extent of Necrosis in the Treated Lesions)
Measured: 1 year
Hepatic Progression Free Survival
Data not collected - study terminated ealry
Measured: 1 year
Change in Tumor Marker
Measured: 1 year
Performance Status (ECOG)
No data collected
Measured: 1 year
Overall Survival
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jan 2009 (estimated)
- Study startDec 2008
- Primary completionJan 2011
- Study completionMar 2011
Why it stopped: Lack of enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Unresectable Metastatic Colo-rectal CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- Generic Devices Consulting, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Biocompatibles UK Ltd
- Responsible party
- Sponsor
- Investigators
- Wells Messersmith, MD, Principal investigator, University of Colorado, Denver
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00816777
- Sponsor's protocol ID
- CA1013
- Other IDs
- IDE G070122
- Acronym
- PARAGON
- Status last verified
- Feb 2018
- First submitted
- 2 Jan 2009
- Last updated
- 7 Sep 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT00816777
- Acronym / sponsor ID
- PARAGON / CA1013
- Keywords
- Cancer, Carcinoma, Colon Cancer, Colorectal Cancer, Gastric Cancer, Gastrointestinal Cancer, Metastases, Metastatic Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of enrollment
- Enrolment
- 4 participants (actual)
- Lead sponsor
- Generic Devices Consulting, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Biocompatibles UK Ltd
- Study start
- Dec 2008
- Primary completion
- Jan 2011 (actual)
- Study completion
- Mar 2011 (actual)
- First posted
- 5 Jan 2009 (estimated)
- Results
- Posted 18 Sep 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of this study is to evaluate the safety and efficacy of Irinotecan Bead in combination with intravenous chemotherapy versus intravenous chemotherapy alone in the treatment of unresectable liver metastases in patients with colorectal cancer. The results of this study are intended to be used in support of a PMA application for a combination device
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Chemoembolization | Experimental | Procedure: Chemoembolization with irinotecan Bead, Drug: IrinotecanChemoembolization with Irinotecan Bead in combination with Intravenous Chemotherapy Group (test arm) |
| Chemotherapy | Active comparator | Drug: IrinotecanIrinotecan monotherapy: 250mg/m2 repeated every 3 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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
Key exclusion criteria (21 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Chemoembolization with irinotecan BeadAlso: Trans arterial Chemoembolization, Irinotecan BeadIntra arterial chemoembolization using Irinotecan Bead 100mg irinotecan per procedure in combination with irinotecan monotherapy 250mg/m2 alternating on a 3 weekly schedule | Procedure or surgery | Chemoembolization |
| IrinotecanAlso: camptosarIrinotecan monotherapy: 250mg/m2 repeated every 3 weeks | Drug | Chemoembolization, Chemotherapy |
Primary outcome
Progression Free Survival
Time frame: 1 year
7 secondary outcomes
Toxicity, Adverse Events and Serious Adverse Events (NCI CTCAE v3.0)
Time frame: 6 weeks
Tumor Response (RECIST)
Time frame: 1 year
Local Tumor Response (Extent of Necrosis in the Treated Lesions)
Time frame: 1 year
Hepatic Progression Free Survival
Time frame: 1 year
Change in Tumor Marker
Time frame: 1 year
Performance Status (ECOG)
Time frame: 1 year
Overall Survival
Time frame: 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Sep 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Wells Messersmith, MD principal investigator
University of Colorado, Denver
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Chemoembolization with irinotecan Bead and Irinotecan in people with Unresectable Metastatic Colo-rectal Cancer, run by Generic Devices Consulting, Inc. at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 7 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Sep 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression Free Survival (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Sep 2018.