Neoplasm MetastasesPhase 1NCT01336985
Safety and Pharmacokinetics of Treating Liver Cancer With Drug-Eluting Beads
A Phase 1 study testing Irinotecan, Chemoembolization and Drug-Eluting Beads in people with Neoplasm Metastases and Melanoma, run by National Institutes of Health Clinical Center (CC) at 1 site in United States.
Trial summary
Background: Cancers in other parts of the body often spread to the liver, developing tumors which in many instances cannot be removed with surgery. Liver chemoembolization is a treatment that is routinely performed to control liver tumors in those who cannot have surgery. Read more about this study
- Who is it for?
- Ages 18 to 84 years
- Conditions the study is for
- Neoplasm Metastases, Melanoma, Colorectal Neoplasms
- What is being tested?
- Irinotecan, Chemoembolization and Drug-Eluting Beads
- Type of treatment
- Medical device, Surgery or procedure
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Mar 2011to 28 Mar 2011
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 to 84 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with pathologically proven hepatic-dominant metastases from abdominal or gastrointestinal tract primary malignancy or melanoma where the life limiting component of the disease is hepatic metastasis
- Patients must have unresectable hepatic lesions or must be unable or unwilling to undergo surgical resection. Patients may have undergone prior wedge resection of the liver for metastatic disease
- All patients must be refractory to or intolerant of approved standard systemic therapy.
- Specifically:
- Patients with metastatic colorectal must have received 5-FU and leucovorin in combination with either oxaliplatin and/or irinotecan, since level 1 evidence support increase survival with these regimens, compared to 5-FU and leucovorin alone.
- Patients with melanoma must have received IL-2 or other immunotherapy options (such as ipilimumab or adoptive cell therapy) that have been reported to have efficacy.
Show all 26Show fewer
- Patients with extrahepatic metastases or an unresected primary lesion will be considered eligible if the extrahepatic disease is minimal
- Extent of hepatic metastases is <60% of total hepatic volume.
- Patients must have at least one lesion that can be readily biopsied (at least 10mm diameter)
- ECOG performance status less than or equal to 2
- Life expectancy > 3 months
- At least 18 years of age
- Age < 85 years
- Patients must have had no chemotherapy, radiotherapy, or biologic therapy for their malignancy for at least 4 weeks (or until response can be adequately assessed) prior to treatment and must have recovered from all clinically significant side effects of therapeutic and diagnostic interventions. Anti-VEGF agents (eg, Avastin) may not be administered less than 4 weeks prior to DEB-TACE treatment.
- Patients are not to receive conventional chemotherapy or therapeutic monoclonal antibodies while receiving protocol treatment
- Hematology:
- Absolute neutrophil count greater than 1500/mm(3) without the support of Filgrastim.
- Platelet count greater than 75,000/mm(3).
- Hemoglobin greater than 8.0 g/dl.
- -Chemistry:
- Serum ALT/AST less than or equal to 3 times the upper limit of normal.
- Serum creatinine less than or equal to 2.0 mg/dl unless the measured creatinine clearance is greater than 60 mL/min
- Total bilirubin less than or equal to 2 mg/dl.
- INR <1.5
- PTT less than or equal to 1.3 times control unless a mixing study confirms the presence of a lupus anticoagulant as the cause for the prolonged PTT.
- Screening electrocardiogram is normal with QTc less than or equal to 480msec).
Who cannot join
- Significant cardiac or pulmonary insufficiency as evidenced by
- history of congestive heart failure with an LVEF < 40%
- history of COPD or other chronic pulmonary disease with PFT s indicating an FEV1 less than 30% or a DLCO less than 40% predicted for age
- Portal Vein Occlusion or other contraindications to chemoembolization
- Inflammatory bowel disease
- Prior chemoembolization therapy
Show all 18Show fewer
- Prior precutaneous hepatic perfusion therapy
- Prior selective internal radiation therapy (SIRT) with Yttrium-90
- Prior biliary diversion surgery
- Previous liver resection other than wedge resection.
- Pregnant patients and nursing mothers will be excluded because of the unknown effects of this therapy on the fetus or nursing infants.
- Patients taking immunosuppressive drugs or requiring ongoing chronic anticoagulation will not be eligible.
- Patients with active bacterial infections with systemic manifestations (malaise, fever, leucocytosis) are not eligible until completion of appropriate therapy.
- Patients with severe allergic reactions to iodine contrast which cannot be controlled by premedication with antihistamines and steroids are not eligible as a hepatic angiogram is needed for this procedure.
- Patients with a known prior hypersensitivity reaction or other contraindication to irinotecan will be excluded.
- Patients taking phenytoin, phenobarbital, carbamazepine, rifampin, rifabutin, St. John s Wort, or other CYP3A inducers or inhibitors are not eligible for this study.
- Patients are prohibited from receiving other experimental agents/adjuvant treatments during the study.
- Patients with more than one active primary malignancy, except for basal cell carcinoma or superficial bladder neoplasia, are to be excluded.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Phase Ib Study of the Safety and Pharmacokinetics of Chemoembolization With Irinotecan-Eluting Beads for the Treatment of Hepatic Metastases
Background:
- Cancers in other parts of the body often spread to the liver, developing tumors which in many instances cannot be removed with surgery. Liver chemoembolization is a treatment that is routinely performed to control liver tumors in those who cannot have surgery. It has been shown to prolong survival, but does not cure the cancer. During chemoembolization very tiny beads (drug-eluting beads, or DEB) containing chemotherapy drugs (usually doxorubicin) are administered directly into the blood vessels of a liver tumor. The drug within the beads is then released into the tumor whilethe beads temporarily interrupt the tumor s blood supply.
- Irinotecan, a drug commonly given intravenously to treat colon cancer, has been given in chemoembolization procedures in four other studies that have shown that the treatment is generally well tolerated. Researchers are interested in determining whether giving the drug irinotecan directly into the liver using drug-eluting beads is not only well tolerated but also provides a larger dose directly to the tumor as determined by tumor and normal liver tissue biopsies. The liver biopsies are an optional portion of the study.
Read more
Objectives:
- To evaluate the safety and effectiveness of chemoembolization with irinotecan for tumors caused by cancer that has spread to the liver.
Eligibility:
- Individuals at least 18 years of age who have melanoma, colon, or another intra-abdominal cancer that has spread to the liver.
Design:
- Participants will be screened with a physical examination, medical history, blood tests, tumor imaging studies, and liver biopsies.
- Participants will receive up to 3 DEB chemoembolization treatments about 6 weeks apart.
- After two treatments, participants will have imaging studies to see if the tumors have shrunk, and those whose tumors have shrunk may have a third treatment.
- Multiple liver biopsies may be performed and blood samples will be taken to determine how much drug is in the tumor and the circulation, and to see how the tumor reacts to the drug.
- Participants will return for followup visits for up to 1 year....
Read the detailed description
Background:
- Clinical evidence suggests that hepatic chemoembolization may prolong survival in patients with hepatic metastases.
- Early studies have indicated that chemoembolization using irinotecan drug eluting beads may be more effective in treating hepatic metastases from colon or melanoma primary tumors.
Objectives:
- Primary Objective: --To determine the safety of hepatic chemoembolization with drug-eluting beads containing 100mg of irinotecan
- Secondary Objectives:
- To determine the serum pharmacokinetics and tumor tissue concentrations achieved following hepatic chemoembolization with irinotecan-eluting beads
Eligibility:
- Patients > 18 years of age with pathologically proven hepatic metastases from the gastrointestinal tract, or melanoma with unresectable hepatic lesions.
- Patients whose extent of hepatic metastases represents <60% of total liver volume AND whose extrahepatic metastatic disease is determined to be minimal
- Patients must be ECOG performance status of less than or equal to 2 and a life expectancy of more than 3 months.
- Patients must have adequate organ function.
- Patients must not have had chemotherapy, radiation therapy, or biological therapy for at least 4 weeks prior to starting study treatments.
- Patients are not to receive conventional chemotherapy or therapeutic monoclonal antibodies while on study.
- Patients must not have an acute, critical illness.
Design:
- A Phase Ib trial in which patients undergo hepatic chemoembolization with drug-eluting beads containing 100mg irinotecan.
- Up to 15 patients will be enrolled over 1 year to accrue 10 evaluable patients.
- Patients will undergo up to 3 chemoembolizations.
- Following chemoembolization, patients will have serial serum pharmacokinetic samples drawn and tumor biopsies in order to measure serum and tumor tissue concentrations of irinotecan
- Patients will be followed for one year after completion of the last treatment.
- Conditions
- Neoplasm Metastases, Melanoma, Colorectal Neoplasms
- Being tested
- Irinotecan, Chemoembolization, Drug-Eluting Beads, Biopsy
- Keywords
- Chemoembolization, Hepatic Metastases, Irinotecan, Drug Eluding Beads, Colorectal Cancer, Liver Cancer, Hepatic Cancer, Melanoma
- Medical subject headings
- Neoplasm Metastasis, Melanoma, Colorectal Neoplasms, Liver Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IrinotecanDrug
ChemoembolizationProcedure or surgery
Drug-Eluting BeadsDevice
BiopsyProcedure or surgery
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the safety of hepatic chemoembolization with drug-eluting beads containing 100mg of irinotecan
Secondary outcomes (1)
To determine the serum pharmacokinetics and tumor tissue concentrations achieved following hepatic chemoembolization with irinotecan-eluting beads
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Apr 2011 (estimated)
- Study start28 Mar 2011
- Study completion28 Mar 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Neoplasm MetastasesStudies 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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institutes of Health Clinical Center (CC)
- Sponsor type
- US National Institutes of Health
- Investigators
- Elliot B Levy, M.D., Principal investigator, National Institutes of Health Clinical Center (CC)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01336985
- Sponsor's protocol ID
- 110131
- Other IDs
- 11-CC-0131
- Status last verified
- 3 Nov 2014
- First submitted
- 14 Apr 2011
- Last updated
- 17 Dec 2019
- Results posted
- No
Publications
Adam R, Delvart V, Pascal G, Valeanu A, Castaing D, Azoulay D, Giacchetti S, Paule B, Kunstlinger F, Ghemard O, Levi F, Bismuth H. Rescue surgery for unresectable colorectal liver metastases downstaged by chemotherapy: a model to predict long-term survival. Ann Surg. 2004 Oct;240(4):644-57; discussion 657-8. doi: 10.1097/01.sla.0000141198.92114.f6.
PubMed 15383792Adam R. Chemotherapy and surgery: new perspectives on the treatment of unresectable liver metastases. Ann Oncol. 2003;14 Suppl 2:ii13-6. doi: 10.1093/annonc/mdg731.
PubMed 12810452Aliberti C, Tilli M, Benea G, Fiorentini G. Trans-arterial chemoembolization (TACE) of liver metastases from colorectal cancer using irinotecan-eluting beads: preliminary results. Anticancer Res. 2006 Sep-Oct;26(5B):3793-5.
PubMed 17094403
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase Ib Study of the Safety and Pharmacokinetics of Chemoembolization With Irinotecan-Eluting Beads for the Treatment of Hepatic Metastases
- ClinicalTrials.gov ID
- NCT01336985
- Acronym / sponsor ID
- 110131
- Conditions
- Neoplasm Metastases, Melanoma, Colorectal Neoplasms
- Keywords
- Chemoembolization, Hepatic Metastases, Irinotecan, Drug Eluding Beads, Colorectal Cancer, Liver Cancer, Hepatic Cancer, Melanoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 5 participants (actual)
- Lead sponsor
- National Institutes of Health Clinical Center (CC)US National Institutes of Health
- Study start
- 28 Mar 2011
- Study completion
- 28 Mar 2011 (actual)
- First posted
- 18 Apr 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
- Cancers in other parts of the body often spread to the liver, developing tumors which in many instances cannot be removed with surgery. Liver chemoembolization is a treatment that is routinely performed to control liver tumors in those who cannot have surgery. It has been shown to prolong survival, but does not cure the cancer. During chemoembolization very tiny beads (drug-eluting beads, or DEB) containing chemotherapy drugs (usually doxorubicin) are administered directly into the blood vessels of a liver tumor. The drug within the beads is then released into the tumor whilethe beads temporarily interrupt the tumor s blood supply.
- Irinotecan, a drug commonly given intravenously to treat colon cancer, has been given in chemoembolization procedures in four other studies that have shown that the treatment is generally well tolerated. Researchers are interested in determining whether giving the drug irinotecan directly into the liver using drug-eluting beads is not only well tolerated but also provides a larger dose directly to the tumor as determined by tumor and normal liver tissue biopsies. The liver biopsies are an optional portion of the study.
Objectives:
- To evaluate the safety and effectiveness of chemoembolization with irinotecan for tumors caused by cancer that has spread to the liver.
Eligibility:
- Individuals at least 18 years of age who have melanoma, colon, or another intra-abdominal cancer that has spread to the liver.
Design:
- Participants will be screened with a physical examination, medical history, blood tests, tumor imaging studies, and liver biopsies.
- Participants will receive up to 3 DEB chemoembolization treatments about 6 weeks apart.
- After two treatments, participants will have imaging studies to see if the tumors have shrunk, and those whose tumors have shrunk may have a third treatment.
- Multiple liver biopsies may be performed and blood samples will be taken to determine how much drug is in the tumor and the circulation, and to see how the tumor reacts to the drug.
- Participants will return for followup visits for up to 1 year....
Detailed description
Background:
- Clinical evidence suggests that hepatic chemoembolization may prolong survival in patients with hepatic metastases.
- Early studies have indicated that chemoembolization using irinotecan drug eluting beads may be more effective in treating hepatic metastases from colon or melanoma primary tumors.
Objectives:
- Primary Objective: --To determine the safety of hepatic chemoembolization with drug-eluting beads containing 100mg of irinotecan
- Secondary Objectives:
- To determine the serum pharmacokinetics and tumor tissue concentrations achieved following hepatic chemoembolization with irinotecan-eluting beads
Eligibility:
- Patients > 18 years of age with pathologically proven hepatic metastases from the gastrointestinal tract, or melanoma with unresectable hepatic lesions.
- Patients whose extent of hepatic metastases represents <60% of total liver volume AND whose extrahepatic metastatic disease is determined to be minimal
- Patients must be ECOG performance status of less than or equal to 2 and a life expectancy of more than 3 months.
- Patients must have adequate organ function.
- Patients must not have had chemotherapy, radiation therapy, or biological therapy for at least 4 weeks prior to starting study treatments.
- Patients are not to receive conventional chemotherapy or therapeutic monoclonal antibodies while on study.
- Patients must not have an acute, critical illness.
Design:
- A Phase Ib trial in which patients undergo hepatic chemoembolization with drug-eluting beads containing 100mg irinotecan.
- Up to 15 patients will be enrolled over 1 year to accrue 10 evaluable patients.
- Patients will undergo up to 3 chemoembolizations.
- Following chemoembolization, patients will have serial serum pharmacokinetic samples drawn and tumor biopsies in order to measure serum and tumor tissue concentrations of irinotecan
- Patients will be followed for one year after completion of the last treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 to 84 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (26 listed)
- Patients with pathologically proven hepatic-dominant metastases from abdominal or gastrointestinal tract primary malignancy or melanoma where the life limiting component of the disease is hepatic metastasis
- Patients must have unresectable hepatic lesions or must be unable or unwilling to undergo surgical resection. Patients may have undergone prior wedge resection of the liver for metastatic disease
- All patients must be refractory to or intolerant of approved standard systemic therapy.
- Patients with metastatic colorectal must have received 5-FU and leucovorin in combination with either oxaliplatin and/or irinotecan, since level 1 evidence support increase survival with these regimens, compared to 5-FU and leucovorin alone.
- Patients with melanoma must have received IL-2 or other immunotherapy options (such as ipilimumab or adoptive cell therapy) that have been reported to have efficacy.
Key exclusion criteria (18 listed)
- Significant cardiac or pulmonary insufficiency as evidenced by
- Portal Vein Occlusion or other contraindications to chemoembolization
- Inflammatory bowel disease
- Prior chemoembolization therapy
- Prior precutaneous hepatic perfusion therapy
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 |
|---|---|---|
| Irinotecan | Drug | – |
| Chemoembolization | Procedure or surgery | – |
| Drug-Eluting Beads | Device | – |
| Biopsy | Procedure or surgery | – |
Primary outcome
To determine the safety of hepatic chemoembolization with drug-eluting beads containing 100mg of irinotecan
1 secondary outcome
To determine the serum pharmacokinetics and tumor tissue concentrations achieved following hepatic chemoembolization with irinotecan-eluting beads
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2019.
- Background: PubMed 15383792Adam R, Delvart V, Pascal G, Valeanu A, Castaing D, Azoulay D, Giacchetti S, Paule B, Kunstlinger F, Ghemard O, Levi F, Bismuth H. Rescue surgery for unresectable colorectal liver metastases downstaged by chemotherapy: a model to predict long-term survival. Ann Surg. 2004 Oct;240(4):644-57; discussion 657-8. doi: 10.1097/01.sla.0000141198.92114.f6.
- Background: PubMed 12810452Adam R. Chemotherapy and surgery: new perspectives on the treatment of unresectable liver metastases. Ann Oncol. 2003;14 Suppl 2:ii13-6. doi: 10.1093/annonc/mdg731.
- Background: PubMed 17094403Aliberti C, Tilli M, Benea G, Fiorentini G. Trans-arterial chemoembolization (TACE) of liver metastases from colorectal cancer using irinotecan-eluting beads: preliminary results. Anticancer Res. 2006 Sep-Oct;26(5B):3793-5.
Related trials for Neoplasm Metastases
Not yet recruitingPhase 1
Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy
Colorectal Neoplasms, Neoplasms
RecruitingObservational study
A Non-Interventional Study PASS to Characterize Secondary Malignancies of Tcell Origin Following Tisagenlecleucel Therapy
Secondary Malignancies of T-cell Origin
Not yet recruiting
Augmented-Reality ICG Fluorescence Second-Look for Residual Nodal Disease After Axillary Dissection in Breast Cancer
Breast Cancer, Breast Neoplasms
Not yet recruitingPhase 1
GK01 Cell Therapy in Gastric Cancer With Peritoneal Metastasis
Gastric Cancer (GC)
RecruitingObservational study
Real-world Evaluation of the HistoSonics Edison System for Treatment of Liver Tumors Across Multidisciplinary Users (BOOMBOX: Master Study)
Liver Neoplasms, Primary Liver Cancer
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.
Elliot B Levy, M.D. principal investigator
National Institutes of Health Clinical Center (CC)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Irinotecan, Chemoembolization and Drug-Eluting Beads in people with Neoplasm Metastases and Melanoma, run by National Institutes of Health Clinical Center (CC) at 1 site 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 26 inclusion and 18 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 17 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early. Results are not available in the source record.
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?
To determine the safety of hepatic chemoembolization with drug-eluting beads containing 100mg of irinotecan. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01336985, which also lists 3 linked publications.
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 17 Dec 2019.