Gastrointestinal Carcinoid Tumor, Islet Cell Tumor, Metastatic Cancer
Conditions
Keywords
liver metastases, metastatic gastrointestinal carcinoid tumor, regional gastrointestinal carcinoid tumor, islet cell carcinoma, gastrinoma, insulinoma, glucagonoma, pancreatic polypeptide tumor, somatostatinoma
Brief 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. 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.
Interventions
DRUGPVA microporous hydrospheres/doxorubicin hydrochloride
Sponsors
National Cancer Institute (NCI)
Yale University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: Inclusion criteria: * 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 * Recent-interval progression of hepatic liver metastases * No diffuse hepatic neuroendocrine metastases defined as massive ill-defined tumor involvement measuring \> 90% tumor burden
Exclusion criteria
* 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: Inclusion criteria: * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety - Number of CTCAE v3.0 Events 1 Month Post DEB-TACE | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tumor Response (Efficacy) - by Response Evaluation Criteria in Solid Tumors (RECIST) and the European Association for the Study of the Liver (EASL) Criteria | 12 months | 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 |
| Survival | overall survival | Survival outcomes not assessed due to premature termination of study. |
| Biochemical Response - Time to Progression | Time to progression, 12 months | Biochemical response not assessed due to premature termination of study. |
| Symptomatic Response by Assessing Symptom Severity in Patients | Duration of study participation, average of 12 months | 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: 1. \- No symptoms - Patient completely asymptomatic 2. \- Mild symptoms - Patient with symptoms of diarrhea, flushing, or asthma up to 4 times weekly 3. \- Symptoms impact daily living - symptoms of diarrhea, flushing, or asthma up 5-7 weekly 4. \- Severe symptoms - multiple daily symptoms of diarrhea, flushing, or asthma; symptoms require significant reorganization of daily activities 5. \- Disabling symptoms - Patient disabled by multiple attacks and severe symptoms; unable to leave home or requires hospitalization |
Countries
United States
Participant flow
Recruitment details
13 patients were enrolled on this protocol at Johns Hopkins University. This study was terminated early due to high incidence of bilomas in patients receiving TACE treatment.
Participants by arm
| Arm | Count |
|---|---|
| Drug-eluting Bead Transarterial Chemoembolization (DEB-TACE) Patients were treated with DEB-TACE loaded with doxorubicin up to four procedures in 6 months as indicated, for a maximum of six procedures during the course of 2 years. Follow-up clinical examinations, laboratory assessments, and imaging took place 1 month after each DEB-TACE treatment and then every 2 to 3 months for a period of 2 years. Each DEB-TACE procedure used a maximum of 100mg doxorubicin loaded onto 100-300um LC Beads. | 13 |
| Total | 13 |
Baseline characteristics
| Characteristic | Drug-eluting Bead Transarterial Chemoembolization (DEB-TACE) |
|---|---|
| Age, Continuous | 64 years |
| Region of Enrollment United States | 13 Participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 13 |
| other Total, other adverse events | 13 / 13 |
| serious Total, serious adverse events | 7 / 13 |
Outcome results
Primary
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.
Time frame: 1 month after initial DEB-TACE treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Drug-eluting Bead Transarterial Chemoembolization (DEB-TACE) | Safety - Number of CTCAE v3.0 Events 1 Month Post DEB-TACE | Constipation | 1 number of adverse events |
| Drug-eluting Bead Transarterial Chemoembolization (DEB-TACE) | Safety - Number of CTCAE v3.0 Events 1 Month Post DEB-TACE | Diarrhea | 1 number of adverse events |
| Drug-eluting Bead Transarterial Chemoembolization (DEB-TACE) | Safety - Number of CTCAE v3.0 Events 1 Month Post DEB-TACE | Liver abscess | 1 number of adverse events |
| Drug-eluting Bead Transarterial Chemoembolization (DEB-TACE) | Safety - Number of CTCAE v3.0 Events 1 Month Post DEB-TACE | Hyperglycemia | 5 number of adverse events |
| Drug-eluting Bead Transarterial Chemoembolization (DEB-TACE) | Safety - Number of CTCAE v3.0 Events 1 Month Post DEB-TACE | Pain - other | 1 number of adverse events |
| Drug-eluting Bead Transarterial Chemoembolization (DEB-TACE) | Safety - Number of CTCAE v3.0 Events 1 Month Post DEB-TACE | Dyspnea | 1 number of adverse events |
| Drug-eluting Bead Transarterial Chemoembolization (DEB-TACE) | Safety - Number of CTCAE v3.0 Events 1 Month Post DEB-TACE | Anemia | 1 number of adverse events |
| Drug-eluting Bead Transarterial Chemoembolization (DEB-TACE) | Safety - Number of CTCAE v3.0 Events 1 Month Post DEB-TACE | Lymphopenia | 2 number of adverse events |
| Drug-eluting Bead Transarterial Chemoembolization (DEB-TACE) | Safety - Number of CTCAE v3.0 Events 1 Month Post DEB-TACE | Hypotension | 1 number of adverse events |
| Drug-eluting Bead Transarterial Chemoembolization (DEB-TACE) | Safety - Number of CTCAE v3.0 Events 1 Month Post DEB-TACE | Edema | 2 number of adverse events |
| Drug-eluting Bead Transarterial Chemoembolization (DEB-TACE) | Safety - Number of CTCAE v3.0 Events 1 Month Post DEB-TACE | Increased INR | 2 number of adverse events |
| Drug-eluting Bead Transarterial Chemoembolization (DEB-TACE) | Safety - Number of CTCAE v3.0 Events 1 Month Post DEB-TACE | Fatigue | 9 number of adverse events |
| Drug-eluting Bead Transarterial Chemoembolization (DEB-TACE) | Safety - Number of CTCAE v3.0 Events 1 Month Post DEB-TACE | Fever | 4 number of adverse events |
| Drug-eluting Bead Transarterial Chemoembolization (DEB-TACE) | Safety - Number of CTCAE v3.0 Events 1 Month Post DEB-TACE | Night sweats | 6 number of adverse events |
| Drug-eluting Bead Transarterial Chemoembolization (DEB-TACE) | Safety - Number of CTCAE v3.0 Events 1 Month Post DEB-TACE | Alopecia | 3 number of adverse events |
| Drug-eluting Bead Transarterial Chemoembolization (DEB-TACE) | Safety - Number of CTCAE v3.0 Events 1 Month Post DEB-TACE | Dry skin | 1 number of adverse events |
| Drug-eluting Bead Transarterial Chemoembolization (DEB-TACE) | Safety - Number of CTCAE v3.0 Events 1 Month Post DEB-TACE | Ascites | 1 number of adverse events |
| Drug-eluting Bead Transarterial Chemoembolization (DEB-TACE) | Safety - Number of CTCAE v3.0 Events 1 Month Post DEB-TACE | Anorexia | 5 number of adverse events |
| Drug-eluting Bead Transarterial Chemoembolization (DEB-TACE) | Safety - Number of CTCAE v3.0 Events 1 Month Post DEB-TACE | Biloma | 6 number of adverse events |
| Drug-eluting Bead Transarterial Chemoembolization (DEB-TACE) | Safety - Number of CTCAE v3.0 Events 1 Month Post DEB-TACE | Nausea | 1 number of adverse events |
| Drug-eluting Bead Transarterial Chemoembolization (DEB-TACE) | Safety - Number of CTCAE v3.0 Events 1 Month Post DEB-TACE | Taste alteration | 1 number of adverse events |
| Drug-eluting Bead Transarterial Chemoembolization (DEB-TACE) | Safety - Number of CTCAE v3.0 Events 1 Month Post DEB-TACE | Hematoma | 1 number of adverse events |
| Drug-eluting Bead Transarterial Chemoembolization (DEB-TACE) | Safety - Number of CTCAE v3.0 Events 1 Month Post DEB-TACE | Increased ALT | 5 number of adverse events |
| Drug-eluting Bead Transarterial Chemoembolization (DEB-TACE) | Safety - Number of CTCAE v3.0 Events 1 Month Post DEB-TACE | Increased AST | 5 number of adverse events |
| Drug-eluting Bead Transarterial Chemoembolization (DEB-TACE) | Safety - Number of CTCAE v3.0 Events 1 Month Post DEB-TACE | Increased AP | 8 number of adverse events |
| Drug-eluting Bead Transarterial Chemoembolization (DEB-TACE) | Safety - Number of CTCAE v3.0 Events 1 Month Post DEB-TACE | Hyperbilirubinemia | 1 number of adverse events |
| Drug-eluting Bead Transarterial Chemoembolization (DEB-TACE) | Safety - Number of CTCAE v3.0 Events 1 Month Post DEB-TACE | Hypoalbuminemia | 5 number of adverse events |
| Drug-eluting Bead Transarterial Chemoembolization (DEB-TACE) | Safety - Number of CTCAE v3.0 Events 1 Month Post DEB-TACE | Hyponatremia | 1 number of adverse events |
| Drug-eluting Bead Transarterial Chemoembolization (DEB-TACE) | Safety - Number of CTCAE v3.0 Events 1 Month Post DEB-TACE | Neuropathy | 1 number of adverse events |
| Drug-eluting Bead Transarterial Chemoembolization (DEB-TACE) | Safety - Number of CTCAE v3.0 Events 1 Month Post DEB-TACE | Abdominal nonspecific pain | 5 number of adverse events |
| Drug-eluting Bead Transarterial Chemoembolization (DEB-TACE) | Safety - Number of CTCAE v3.0 Events 1 Month Post DEB-TACE | Right upper quadrant pain | 6 number of adverse events |
| Drug-eluting Bead Transarterial Chemoembolization (DEB-TACE) | Safety - Number of CTCAE v3.0 Events 1 Month Post DEB-TACE | Dyspnea on exertion | 1 number of adverse events |
Secondary
Biochemical Response - Time to Progression
Biochemical response not assessed due to premature termination of study.
Time frame: Time to progression, 12 months
Secondary
Survival
Survival outcomes not assessed due to premature termination of study.
Time frame: overall survival
Secondary
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: 1. \- No symptoms - Patient completely asymptomatic 2. \- Mild symptoms - Patient with symptoms of diarrhea, flushing, or asthma up to 4 times weekly 3. \- Symptoms impact daily living - symptoms of diarrhea, flushing, or asthma up 5-7 weekly 4. \- Severe symptoms - multiple daily symptoms of diarrhea, flushing, or asthma; symptoms require significant reorganization of daily activities 5. \- Disabling symptoms - Patient disabled by multiple attacks and severe symptoms; unable to leave home or requires hospitalization
Time frame: Duration of study participation, average of 12 months
Secondary
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
Time frame: 12 months
Population: 13 patients were analyzed for 1 month post-treatment; 10 patients for 6 months post-treatment; and 6 patients at the 12 month post-treatment time point.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Drug-eluting Bead Transarterial Chemoembolization (DEB-TACE) | Tumor Response (Efficacy) - by Response Evaluation Criteria in Solid Tumors (RECIST) and the European Association for the Study of the Liver (EASL) Criteria | RECIST 1 month post-TACE | Complete Response (CR) | 0 Participants |
| Drug-eluting Bead Transarterial Chemoembolization (DEB-TACE) | Tumor Response (Efficacy) - by Response Evaluation Criteria in Solid Tumors (RECIST) and the European Association for the Study of the Liver (EASL) Criteria | RECIST 1 month post-TACE | Partial Response (PR) | 0 Participants |
| Drug-eluting Bead Transarterial Chemoembolization (DEB-TACE) | Tumor Response (Efficacy) - by Response Evaluation Criteria in Solid Tumors (RECIST) and the European Association for the Study of the Liver (EASL) Criteria | RECIST 6 months post-TACE | Partial Response (PR) | 1 Participants |
| Drug-eluting Bead Transarterial Chemoembolization (DEB-TACE) | Tumor Response (Efficacy) - by Response Evaluation Criteria in Solid Tumors (RECIST) and the European Association for the Study of the Liver (EASL) Criteria | RECIST 12 months post-TACE | Progressive Disease | 1 Participants |
| Drug-eluting Bead Transarterial Chemoembolization (DEB-TACE) | Tumor Response (Efficacy) - by Response Evaluation Criteria in Solid Tumors (RECIST) and the European Association for the Study of the Liver (EASL) Criteria | EASL 12 months post-TACE | Partial Response (PR) | 1 Participants |
| Drug-eluting Bead Transarterial Chemoembolization (DEB-TACE) | Tumor Response (Efficacy) - by Response Evaluation Criteria in Solid Tumors (RECIST) and the European Association for the Study of the Liver (EASL) Criteria | RECIST 1 month post-TACE | Stable Disease (SD) | 13 Participants |
| Drug-eluting Bead Transarterial Chemoembolization (DEB-TACE) | Tumor Response (Efficacy) - by Response Evaluation Criteria in Solid Tumors (RECIST) and the European Association for the Study of the Liver (EASL) Criteria | RECIST 1 month post-TACE | Progressive Disease | 0 Participants |
| Drug-eluting Bead Transarterial Chemoembolization (DEB-TACE) | Tumor Response (Efficacy) - by Response Evaluation Criteria in Solid Tumors (RECIST) and the European Association for the Study of the Liver (EASL) Criteria | EASL 1 month post-TACE | Complete Response (CR) | 0 Participants |
| Drug-eluting Bead Transarterial Chemoembolization (DEB-TACE) | Tumor Response (Efficacy) - by Response Evaluation Criteria in Solid Tumors (RECIST) and the European Association for the Study of the Liver (EASL) Criteria | EASL 1 month post-TACE | Partial Response (PR) | 8 Participants |
| Drug-eluting Bead Transarterial Chemoembolization (DEB-TACE) | Tumor Response (Efficacy) - by Response Evaluation Criteria in Solid Tumors (RECIST) and the European Association for the Study of the Liver (EASL) Criteria | EASL 1 month post-TACE | Stable Disease (SD) | 5 Participants |
| Drug-eluting Bead Transarterial Chemoembolization (DEB-TACE) | Tumor Response (Efficacy) - by Response Evaluation Criteria in Solid Tumors (RECIST) and the European Association for the Study of the Liver (EASL) Criteria | EASL 1 month post-TACE | Progressive Disease | 0 Participants |
| Drug-eluting Bead Transarterial Chemoembolization (DEB-TACE) | Tumor Response (Efficacy) - by Response Evaluation Criteria in Solid Tumors (RECIST) and the European Association for the Study of the Liver (EASL) Criteria | RECIST 6 months post-TACE | Complete Response (CR) | 0 Participants |
| Drug-eluting Bead Transarterial Chemoembolization (DEB-TACE) | Tumor Response (Efficacy) - by Response Evaluation Criteria in Solid Tumors (RECIST) and the European Association for the Study of the Liver (EASL) Criteria | RECIST 6 months post-TACE | Stable Disease (SD) | 8 Participants |
| Drug-eluting Bead Transarterial Chemoembolization (DEB-TACE) | Tumor Response (Efficacy) - by Response Evaluation Criteria in Solid Tumors (RECIST) and the European Association for the Study of the Liver (EASL) Criteria | RECIST 6 months post-TACE | Progressive Disease | 1 Participants |
| Drug-eluting Bead Transarterial Chemoembolization (DEB-TACE) | Tumor Response (Efficacy) - by Response Evaluation Criteria in Solid Tumors (RECIST) and the European Association for the Study of the Liver (EASL) Criteria | EASL 6 months post-TACE | Complete Response (CR) | 1 Participants |
| Drug-eluting Bead Transarterial Chemoembolization (DEB-TACE) | Tumor Response (Efficacy) - by Response Evaluation Criteria in Solid Tumors (RECIST) and the European Association for the Study of the Liver (EASL) Criteria | EASL 6 months post-TACE | Partial Response (PR) | 3 Participants |
| Drug-eluting Bead Transarterial Chemoembolization (DEB-TACE) | Tumor Response (Efficacy) - by Response Evaluation Criteria in Solid Tumors (RECIST) and the European Association for the Study of the Liver (EASL) Criteria | EASL 6 months post-TACE | Stable Disease (SD) | 6 Participants |
| Drug-eluting Bead Transarterial Chemoembolization (DEB-TACE) | Tumor Response (Efficacy) - by Response Evaluation Criteria in Solid Tumors (RECIST) and the European Association for the Study of the Liver (EASL) Criteria | EASL 6 months post-TACE | Progressive Disease | 0 Participants |
| Drug-eluting Bead Transarterial Chemoembolization (DEB-TACE) | Tumor Response (Efficacy) - by Response Evaluation Criteria in Solid Tumors (RECIST) and the European Association for the Study of the Liver (EASL) Criteria | RECIST 12 months post-TACE | Complete Response (CR) | 0 Participants |
| Drug-eluting Bead Transarterial Chemoembolization (DEB-TACE) | Tumor Response (Efficacy) - by Response Evaluation Criteria in Solid Tumors (RECIST) and the European Association for the Study of the Liver (EASL) Criteria | RECIST 12 months post-TACE | Partial Response (PR) | 1 Participants |
| Drug-eluting Bead Transarterial Chemoembolization (DEB-TACE) | Tumor Response (Efficacy) - by Response Evaluation Criteria in Solid Tumors (RECIST) and the European Association for the Study of the Liver (EASL) Criteria | RECIST 12 months post-TACE | Stable Disease (SD) | 4 Participants |
| Drug-eluting Bead Transarterial Chemoembolization (DEB-TACE) | Tumor Response (Efficacy) - by Response Evaluation Criteria in Solid Tumors (RECIST) and the European Association for the Study of the Liver (EASL) Criteria | EASL 12 months post-TACE | Complete Response (CR) | 2 Participants |
| Drug-eluting Bead Transarterial Chemoembolization (DEB-TACE) | Tumor Response (Efficacy) - by Response Evaluation Criteria in Solid Tumors (RECIST) and the European Association for the Study of the Liver (EASL) Criteria | EASL 12 months post-TACE | Stable Disease (SD) | 3 Participants |
| Drug-eluting Bead Transarterial Chemoembolization (DEB-TACE) | Tumor Response (Efficacy) - by Response Evaluation Criteria in Solid Tumors (RECIST) and the European Association for the Study of the Liver (EASL) Criteria | EASL 12 months post-TACE | Progressive Disease | 0 Participants |