Gastrointestinal Carcinoid TumorNCT00730483
Doxorubicin Beads in Treating Patients With Unresectable Liver Metastases From Neuroendocrine Tumors
A study testing PVA microporous hydrospheres/doxorubicin hydrochloride in people with Gastrointestinal Carcinoid Tumor and Islet Cell Tumor, run by Yale University at 1 site in United States.
Trial summary
RATIONALE: Drugs used in chemotherapy, such as doxorubicin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Gastrointestinal Carcinoid Tumor, Islet Cell Tumor, Metastatic Cancer
- What is being tested?
- PVA microporous hydrospheres/doxorubicin hydrochloride
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2009to Jun 2014
- Phase
- Interventional
- 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 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of hepatic neuroendocrine metastases not suitable for radical therapies (e.g., resection or liver transplantation)
- Histologically proven neuroendocrine tumor
- Tumors are hypervascular based on visual estimation by investigator
- Predominant to the liver disease, but extrahepatic disease is not an exclusion
- No predominant extrahepatic liver disease
- No significant life-threatening extrahepatic disease, in the judgment of the physician
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- Recent-interval progression of hepatic liver metastases
- No diffuse hepatic neuroendocrine metastases defined as massive ill-defined tumor involvement measuring > 90% tumor burden
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Must have preserved liver function (Child-Pugh class A-B) without significant liver decompensation
- No advanced liver disease (e.g., Child-Pugh C class or active gastrointestinal bleeding, encephalopathy, or ascites [trace ascites is acceptable]), meeting the following criteria:
- Bilirubin > 3 mg/dL
- Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase > 5 times upper limit of normal
- Serum creatinine > 2.0 mg/dL
- Albumin ≤ 2.0 g/dL
- No vascular anatomy or blood that precludes catheter placement or emboli injection
- No presence of arteries supplying the lesion not large enough to accept PVA microporous hydrospheres/doxorubicin hydrochloride
- No collateral vessel pathways potentially endangering normal territories during embolization
- No feeding arteries smaller than distal branches from which they emerge
- Not pregnant
Who cannot join
- Clinically evident ascites (a radiographic finding of trace ascites on imaging is acceptable)
- Complete occlusion of the entire portal venous system
- Evidence of cirrhosis or portal hypertension
- Vascular resistance peripheral to the feeding arteries precluding passage of PVA microporous hydrospheres/doxorubicin hydrochloride
- PATIENT CHARACTERISTICS:
- See Disease Characteristics
Show all 28Show fewer
- Another active primary tumor
- Any contraindication for hepatic embolization procedures, including any of the following:
- Porto-systemic shunt
- Hepatofugal blood flow
- Impaired clotting tests (i.e., platelet count < 50,000/mm³, international normalized ratio (INR) ≥ 1.8, or partial thromboplastin time (PTT) ≥ 39 seconds)
- Renal failure
- Severe peripheral vascular disease precluding catheterization
- Any contraindication for doxorubicin hydrochloride administration (i.e., serum bilirubin > 5 mg/dL or leukocyte count < 1,500 cells/mm³)
- Allergy to contrast media
- Intolerant to occlusion procedures
- Presence of end arteries leading directly to cranial nerves
- Presence or likely onset of hemorrhage
- Presence of severe atheromatous disease
- PRIOR CONCURRENT THERAPY:
- Prior anticancer therapy for hepatic neuroendocrine metastases, except previous surgical therapy
- Any continuing complication or prior cancer therapy that has not improved or resolved prior to 21 days before start of treatment, if the investigator determines that the continuing complication will compromise the safety of the patient after treatment with PVA microporous hydrospheres/doxorubicin hydrochloride
- Presence of patent extra-to-intracranial anastomoses or shunts
- Use of PVA microporous hydrospheres/doxorubicin hydrochloride in the following applications:
- Embolization of large-diameter arteriovenous shunts
- Pulmonary arterial vasculature
- Any vasculature where the use of PVA microporous hydrospheres/doxorubicin hydrochloride could pass directly into the internal carotid artery or the above-listed vessels
- Concurrent enrollment in another clinical study
Trial locations and contacts
1 site in 1 country.
United States1 site
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, 21231-2410
About this study
Official title: Treatment of Patients With Hepatic Neuroendocrine Metastases Using Drug-Eluting Bead Embolization
RATIONALE: Drugs used in chemotherapy, such as doxorubicin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Infusing doxorubicin beads into the liver, and blocking blood flow to the tumor, may keep doxorubicin near the tumor and kill more tumor cells.
PURPOSE: This clinical trial is studying the side effects of doxorubicin beads and to see how well they work in treating patients with unresectable liver metastases from neuroendocrine tumors.
Read the detailed description
OBJECTIVES:
Primary
- To gather preliminary data and determine the feasibility of a randomized study of patients with unresectable hepatic neuroendocrine metastases using PVA microporous hydrospheres/doxorubicin hydrochloride.
OUTLINE: A catheter is placed into the right or left hepatic artery. Patients with unifocal tumors will have the catheter or microcatheter placed more selectively into the 2nd or 3rd order branch off the right or left hepatic artery in closer proximity to the tumor. Polyvinyl alcohol (PVA) microporous hydrospheres/doxorubicin hydrochloride mixture is injected into the delivery area.
Patients with less than 75% necrosis at 1 month undergo a second (and possibly a third a month later) chemoembolization.
After completion of study therapy, patients are followed at 1 month, every 2 months for 1 year, and then every 3 months for 1 year.
- Being tested
- PVA microporous hydrospheres/doxorubicin hydrochloride
- Keywords
- liver metastases, metastatic gastrointestinal carcinoid tumor, regional gastrointestinal carcinoid tumor, islet cell carcinoma, gastrinoma, insulinoma, glucagonoma, pancreatic polypeptide tumor, somatostatinoma
- Medical subject headings
- Adenoma, Islet Cell, Neoplasm Metastasis, Carcinoma, Islet Cell, Gastrinoma, Insulinoma, Glucagonoma, Somatostatinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PVA microporous hydrospheres/doxorubicin hydrochlorideDrug
| Study group | Role | What they receive |
|---|---|---|
| DEB-TACE | Experimental | PVA microporous hydrospheres loaded with doxorubicin hydrochloride used for the treatment of unresectable liver metastases from neuroendocrine tumors. Receives: Drug: PVA microporous hydrospheres/doxorubicin hydrochloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety - Number of CTCAE v3.0 Events 1 Month Post DEB-TACE
Safety was assessed at each DEB-TACE procedure and at every follow-up thereafter according to National Cancer Institute Common Toxicity Criteria (CTCAE) v3.0. The study was prematurely terminated due to high incidence of biloma and liver abscess. Safety data below is based off of 13 patients enrolled on protocol at 1 month post initial treatment.
Measured: 1 month after initial DEB-TACE treatment
Secondary outcomes (4)
Tumor Response (Efficacy) - by Response Evaluation Criteria in Solid Tumors (RECIST) and the European Association for the Study of the Liver (EASL) Criteria
Study was terminated and full outcome not assessed. The results below are based on 13 patients at 1 month post DEB-TACE, 10 patients at 6 months, and 6 patients at 12 months.
RECIST:
Complete Response (CR): Disappearance of all targeted lesions Partial Response (PR): At least 30% decrease in the sum of longest diameter (LD) of targeted lesions Progressive Disease (PD): At least 20% increase in the sum of LD of targeted lesions Stable Disease (SD): Cases that are not applicable for PD or PR.
EASL:
CR: Absence of any enhancement in target lesion PR: Greater than 50% decrease from baseline enhancement in target lesion PD: Greater than 25% increase in target lesion SD: All other cases
Measured: 12 months
Survival
Survival outcomes not assessed due to premature termination of study.
Measured: overall survival
Biochemical Response - Time to Progression
Biochemical response not assessed due to premature termination of study.
Measured: Time to progression, 12 months
Symptomatic Response by Assessing Symptom Severity in Patients
Symptomatic response not assessed due to premature termination of study.
Scoring system for assessing symptom severity in patients with neuroendocrine/carcinoid syndrome was as follows:
- - No symptoms - Patient completely asymptomatic
- - Mild symptoms - Patient with symptoms of diarrhea, flushing, or asthma up to 4 times weekly
- - Symptoms impact daily living - symptoms of diarrhea, flushing, or asthma up 5-7 weekly
- - Severe symptoms - multiple daily symptoms of diarrhea, flushing, or asthma; symptoms require significant reorganization of daily activities
- - Disabling symptoms - Patient disabled by multiple attacks and severe symptoms; unable to leave home or requires hospitalization
Measured: Duration of study participation, average of 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Aug 2008 (estimated)
- Study startFeb 2009
- Primary completionJun 2014
- Study completionJun 2014
Why it stopped: High incidence of biloma and liver abscess after TACE
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Gastrointestinal Carcinoid TumorStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Principal investigator, Jeff Geschwind, Yale University
- Investigators
- Jeffrey F. Geschwind, MD, Principal investigator, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00730483
- Sponsor's protocol ID
- J0739 CDR0000601054
- Other IDs
- JHOC-J7039, JHOC-NA_000010736, JHOC-SKCCC-J7039
- Status last verified
- Jul 2017
- First submitted
- 7 Aug 2008
- Last updated
- 25 Aug 2017
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Bhagat N, Reyes DK, Lin M, Kamel I, Pawlik TM, Frangakis C, Geschwind JF. Phase II study of chemoembolization with drug-eluting beads in patients with hepatic neuroendocrine metastases: high incidence of biliary injury. Cardiovasc Intervent Radiol. 2013 Apr;36(2):449-59. doi: 10.1007/s00270-012-0424-y. Epub 2012 Jun 22.
PubMed 22722717
Study at a glance
From the registry record, last updated by the sponsor on 25 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment of Patients With Hepatic Neuroendocrine Metastases Using Drug-Eluting Bead Embolization
- ClinicalTrials.gov ID
- NCT00730483
- Acronym / sponsor ID
- J0739 CDR0000601054
- Keywords
- liver metastases, metastatic gastrointestinal carcinoid tumor, regional gastrointestinal carcinoid tumor, islet cell carcinoma, gastrinoma, insulinoma, glucagonoma, pancreatic polypeptide tumor
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: High incidence of biloma and liver abscess after TACE
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Feb 2009
- Primary completion
- Jun 2014 (actual)
- Study completion
- Jun 2014 (actual)
- First posted
- 8 Aug 2008 (estimated)
- Results
- Posted 25 Aug 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Drugs used in chemotherapy, such as doxorubicin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Infusing doxorubicin beads into the liver, and blocking blood flow to the tumor, may keep doxorubicin near the tumor and kill more tumor cells.
PURPOSE: This clinical trial is studying the side effects of doxorubicin beads and to see how well they work in treating patients with unresectable liver metastases from neuroendocrine tumors.
Detailed description
OBJECTIVES:
Primary
- To gather preliminary data and determine the feasibility of a randomized study of patients with unresectable hepatic neuroendocrine metastases using PVA microporous hydrospheres/doxorubicin hydrochloride.
OUTLINE: A catheter is placed into the right or left hepatic artery. Patients with unifocal tumors will have the catheter or microcatheter placed more selectively into the 2nd or 3rd order branch off the right or left hepatic artery in closer proximity to the tumor. Polyvinyl alcohol (PVA) microporous hydrospheres/doxorubicin hydrochloride mixture is injected into the delivery area.
Patients with less than 75% necrosis at 1 month undergo a second (and possibly a third a month later) chemoembolization.
After completion of study therapy, patients are followed at 1 month, every 2 months for 1 year, and then every 3 months for 1 year.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| DEB-TACE | Experimental | Drug: PVA microporous hydrospheres/doxorubicin hydrochloridePVA microporous hydrospheres loaded with doxorubicin hydrochloride used for the treatment of unresectable liver metastases from neuroendocrine tumors. |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Diagnosis of hepatic neuroendocrine metastases not suitable for radical therapies (e.g., resection or liver transplantation)
- Predominant to the liver disease, but extrahepatic disease is not an exclusion
- Recent-interval progression of hepatic liver metastases
- No diffuse hepatic neuroendocrine metastases defined as massive ill-defined tumor involvement measuring > 90% tumor burden
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
Key exclusion criteria (28 listed)
- Clinically evident ascites (a radiographic finding of trace ascites on imaging is acceptable)
- Complete occlusion of the entire portal venous system
- Evidence of cirrhosis or portal hypertension
- Vascular resistance peripheral to the feeding arteries precluding passage of PVA microporous hydrospheres/doxorubicin hydrochloride
- See Disease Characteristics
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 |
|---|---|---|
| PVA microporous hydrospheres/doxorubicin hydrochloride | Drug | DEB-TACE |
Primary outcome
Safety - Number of CTCAE v3.0 Events 1 Month Post DEB-TACE
Time frame: 1 month after initial DEB-TACE treatment
Safety was assessed at each DEB-TACE procedure and at every follow-up thereafter according to National Cancer Institute Common Toxicity Criteria (CTCAE) v3.0. The study was prematurely terminated due to high incidence of biloma and liver abscess. Safety data below is based off of 13 patients enrolled on protocol at 1 month post initial treatment.
4 secondary outcomes
Tumor Response (Efficacy) - by Response Evaluation Criteria in Solid Tumors (RECIST) and the European Association for the Study of the Liver (EASL) Criteria
Time frame: 12 months
Survival
Time frame: overall survival
Biochemical Response - Time to Progression
Time frame: Time to progression, 12 months
Symptomatic Response by Assessing Symptom Severity in Patients
Time frame: Duration of study participation, average of 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Aug 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 22722717Bhagat N, Reyes DK, Lin M, Kamel I, Pawlik TM, Frangakis C, Geschwind JF. Phase II study of chemoembolization with drug-eluting beads in patients with hepatic neuroendocrine metastases: high incidence of biliary injury. Cardiovasc Intervent Radiol. 2013 Apr;36(2):449-59. doi: 10.1007/s00270-012-0424-y. Epub 2012 Jun 22.
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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.
Jeffrey F. Geschwind, MD principal investigator
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing PVA microporous hydrospheres/doxorubicin hydrochloride in people with Gastrointestinal Carcinoid Tumor and Islet Cell Tumor, run by Yale University 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 20 inclusion and 28 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 25 Aug 2017. 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Aug 2017). 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?
Safety - Number of CTCAE v3.0 Events 1 Month Post DEB-TACE (time frame: 1 month after initial DEB-TACE treatment). 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 NCT00730483, which also lists 1 linked publication.
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 25 Aug 2017.