Bile Duct Neoplasms, Colorectal Neoplasms
Conditions
Keywords
hepatic artery infusion pump, colorectal liver metastases, intrahepatic cholangiocarcinoma, FUDR, floxuridine
Brief summary
Due to discontinuation of the Codman C3000 pump, an alternate device is necessary to continue serving patients in need of hepatic arterial infusion chemotherapy. This study aims to test the safety of hepatic artery infusion pump placement, a standard surgical procedure, and intraarterial chemotherapy initiation with the standard medication floxuridine (FUDR), using the Medtronic Synchromed II pump combined with the Codman arterial catheter in patients with unresectable (not removable by surgery) liver metastases from colorectal cancer and unresectable intrahepatic cholangiocarcinoma. This study will determine if complication and pump loss rates will be similar to previously published rates for the Codman system.
Interventions
DEVICEHepatic artery infusion pump placement using the Synchromed II pump and the Codman tapered arterial catheter.
Patients will undergo surgical hepatic artery infusion pump placement using the Synchromed II pump and the Codman tapered arterial catheter.
DRUGHepatic artery infusion pump floxuridine and dexamethasone
Patients will receive infusion of floxuridine (FUDR) and dexamethasone via hepatic artery infusion through the implanted pump
DRUGSystemic chemotherapy for colorectal liver metastases
Patients will receive disease-appropriate systemic chemotherapy for colorectal liver metastases (FOLFOX, FOLFIRI, or irinotecan/oxaliplatin, or panitumumab if KRAS/NRAS wild type)
DRUGSystemic chemotherapy for intrahepatic cholangiocarcinoma
Patients will receive disease-appropriate systemic chemotherapy for intrahepatic cholangiocarcinoma (gemcitabine/oxaliplatin or gemcitabine alone)
Sponsors
Michael J Cavnar, MD
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Patients with unresectable colorectal liver metastases (arm 1) and unresectable intrahepatic cholangiocarcinoma (arm 2), will undergo hepatic artery infusion pump placement using the Synchromed II pump and the Codman tapered arterial catheter. All patients will receive hepatic artery infusion floxuridine, and then individual arms will receive disease-specific systemic chemotherapy.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients ≥ 18 years of age * Histologically confirmed unresectable colorectal adenocarcinoma metastatic to the liver with no definitive clinical or radiographic evidence of extrahepatic disease. Clinical or radiographic evidence of metastatic disease to peri-hepatic lymph nodes will be allowed, provided it is amenable to resection. (OR) * Histologically confirmed unresectable non-metastatic intrahepatic cholangiocarcinoma, with presence of less than 70% liver involvement. Clinical or radiographic evidence of metastatic disease to peri-hepatic lymph nodes will be allowed, provided it is amenable to resection. * ECOG Performance Status of 0 - 1 * Lab Values ≤ 14 days prior to study enrollment: absolute neutrophil count ≥1,500/mcL AST/ALT \< 2.5 x institutional upper limit of normal (ULN) Platelets ≥ 100,000/mcL Creatinine \< 1.5 mg/dL HGB \> 9 g/dL Total Bilirubin ≤ 1.5 mg/dL * Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. * For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. * Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load * Prior chemotherapy is acceptable if last dose given ≥ 3 weeks prior to study enrollment. * Any investigational agent is acceptable if last dose administered ≥ 3 months before study enrollment.
Exclusion criteria
* Presence of distant metastatic disease confirmed by radiographic evaluation. Clinical or radiographic evidence of metastatic disease to regional peri-hepatic lymph nodes will be allowed, provided it is amenable to resection. * Prior radiation to the liver, including external beam, SBRT, Y90. Prior radiation therapy to the pelvis is acceptable. * Active infection, hepatic encephalopathy * Clinical evidence of portal hypertension (ascites, gastroesophageal varices or portal vein thrombosis; surgically-related ascites does not exclude the patient) * Female patients who are pregnant or lactating - or planning to become pregnant within 6 months after the end of the treatment (female patients of child-bearing potential must have negative pregnancy test ≤72 hours before surgery) * If in the opinion of the treating investigator a patient has any serious medical problems which may preclude receiving this type of treatment * Patients with history or known presence of primary CNS tumors, seizures not well-controlled with standard medical therapy, or history of stroke * Serious or non-healing active wound, ulcer, or bone fracture * Prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the HAIP chemotherapy (i.e., investigational regimen) * Patients with psychiatric illness or social situations that would limit compliance with study requirements. Examples include: active substance abuse, active severe EtOH abuse, etc. * Inability to reliably commit to traveling to Lexington, KY every 2 weeks for duration of the study treatment (6 months). Patient must have readily identifiable, reliable primary and back-up modes of transportation regardless of weather.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Completion of 1st Cycle of Hepatic Artery Chemotherapy | approximately 4 weeks | The percent of patients who complete the 1st cycle of hepatic artery chemotherapy will be tabulated. This is a conglomerate safety endpoint which is a surrogate for any complication that prevents delivery of hepatic artery chemotherapy via the device combination. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 30-day Catheter Malfunction Due to Tubing Disconnect | 30 days | Quantify the percent of patients with inability to meet primary outcome due to catheter disconnects. |
| 30-day Catheter Malfunction Due to Inability to Access Pump | 30 days | Quantify the percent of patients with inability to meet primary outcome due to inability to access pump. |
| Percent of Patients That Require Secondary Intervention in Order to Obtain Primary Pump Function. | Approximately 4 weeks | Percentage of patients who need secondary intervention (IR embolization, revision of pump or tubing) to achieve primary pump function. |
| Percent of Screened Patients That Are Declined Due to High Risk of Failure as Determined by the Psychosocial Assessment Tool. | Immediate, determined at screening visit | Patients are screen using a psychosocial assessment tool for high risk of hepatic artery pump loss/failure, percent declined will be tabulated. |
| Percent Pump Loss Due to Inability to Attend Scheduled Followup Appointments. | Approximately 6 months | Percent of patients that experience pump loss/failure due to inability to attend scheduled followup appointments will be tabulated. |
| 30-day Postoperative Serious Adverse Events Related to Pump Implantation | 30 days | Tabulation of CTCAE serious adverse events attributed to pump implantation |
| Percent of Patients Who Remain on Hepatic Artery Infusion Pump Chemotherapy at 3 Months. | 3 months | The percentage of patients who remain on pump chemotherapy at 3 months will be tabulated. |
| Overall Response Rate at 6 Months | 6 months | RECIST v1.1 will be used to assess overall response rate at 6 months. |
| Percent of Patients Who Are Downstaged and Undergo Surgery | 6 months | The percent of patients who are downstaged and undergo surgery will be tabulated. |
| Percent of Patients Who Remain on Hepatic Artery Infusion Pump Chemotherapy at 6 Months. | 6 months | The percentage of patients who remain on pump chemotherapy at 6months will be tabulated. |
| Number of Interventions (Phone Calls) to Assure Patients Attend Followup Appointments. | 6 months | The number of staff contacts (phone calls) to assure patients keep their followup visits will be tabulated. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Colorectal Liver Metastases Patients with unresectable colorectal liver metastases will undergo hepatic artery infusion pump placement using the Synchromed II pump and the Codman tapered arterial catheter. Patients will then receive hepatic artery infusion floxuridine as well as disease-appropriate systemic chemotherapy (FOLFOX, FOLRIRI, or oxaliplatin/irinotecan, or panitumumab if KRAS/NRAS wild type)
Hepatic artery infusion pump placement using the Synchromed II pump and the Codman tapered arterial catheter.: Patients will undergo surgical hepatic artery infusion pump placement using the Synchromed II pump and the Codman tapered arterial catheter.
Hepatic artery infusion pump floxuridine and dexamethasone: Patients will receive infusion of floxuridine (FUDR) and dexamethasone via hepatic artery infusion through the implanted pump
Systemic chemotherapy for colorectal liver metastases: Patients will receive disease-appropriate systemic chemotherapy for colorectal liver metastases (FOLFOX, FOLFIRI, or irinotecan/oxaliplatin, or panitumumab if KRAS/NRAS wild type) | 17 |
| Intrahepatic Cholangiocarcinoma Patients with unresectable intrahepatic cholangiocarcinoma will undergo hepatic artery infusion pump placement using the Synchromed II pump and the Codman tapered arterial catheter. Patients will then receive hepatic artery infusion floxuridine as well as disease-appropriate systemic chemotherapy (gemcitabine/oxaliplatin or gemcitabine alone)
Hepatic artery infusion pump placement using the Synchromed II pump and the Codman tapered arterial catheter.: Patients will undergo surgical hepatic artery infusion pump placement using the Synchromed II pump and the Codman tapered arterial catheter.
Hepatic artery infusion pump floxuridine and dexamethasone: Patients will receive infusion of floxuridine (FUDR) and dexamethasone via hepatic artery infusion through the implanted pump
Systemic chemotherapy for intrahepatic cholangiocarcinoma: Patients will receive disease-appropriate systemic chemotherapy for intrahepatic cholangiocarcinoma (gemcitabine/oxaliplatin or gemcitabine alone) | 4 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Rapid disease progression after surgery led to liver dysfunction; prevented administration of HAI | 1 | 0 |
Baseline characteristics
| Characteristic | Colorectal Liver Metastases | Total | Intrahepatic Cholangiocarcinoma |
|---|---|---|---|
| Age, Customized 40-70 years | 17 Participants | 21 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 17 Participants | 21 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 16 Participants | 20 Participants | 4 Participants |
| Region of Enrollment United States | 17 participants | 21 participants | 4 participants |
| Sex: Female, Male Female | 8 Participants | 10 Participants | 2 Participants |
| Sex: Female, Male Male | 9 Participants | 11 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 17 | 2 / 4 |
| other Total, other adverse events | 17 / 17 | 4 / 4 |
| serious Total, serious adverse events | 15 / 17 | 2 / 4 |
Outcome results
Primary
Percent Completion of 1st Cycle of Hepatic Artery Chemotherapy
The percent of patients who complete the 1st cycle of hepatic artery chemotherapy will be tabulated. This is a conglomerate safety endpoint which is a surrogate for any complication that prevents delivery of hepatic artery chemotherapy via the device combination.
Time frame: approximately 4 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Colorectal Liver Metastases | Percent Completion of 1st Cycle of Hepatic Artery Chemotherapy | 16 Participants |
| Intrahepatic Cholangiocarcinoma | Percent Completion of 1st Cycle of Hepatic Artery Chemotherapy | 4 Participants |
Secondary
30-day Catheter Malfunction Due to Inability to Access Pump
Quantify the percent of patients with inability to meet primary outcome due to inability to access pump.
Time frame: 30 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Colorectal Liver Metastases | 30-day Catheter Malfunction Due to Inability to Access Pump | 0 Participants |
| Intrahepatic Cholangiocarcinoma | 30-day Catheter Malfunction Due to Inability to Access Pump | 0 Participants |
Secondary
30-day Catheter Malfunction Due to Tubing Disconnect
Quantify the percent of patients with inability to meet primary outcome due to catheter disconnects.
Time frame: 30 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Colorectal Liver Metastases | 30-day Catheter Malfunction Due to Tubing Disconnect | 0 Participants |
| Intrahepatic Cholangiocarcinoma | 30-day Catheter Malfunction Due to Tubing Disconnect | 0 Participants |
Secondary
30-day Postoperative Serious Adverse Events Related to Pump Implantation
Tabulation of CTCAE serious adverse events attributed to pump implantation
Time frame: 30 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Colorectal Liver Metastases | 30-day Postoperative Serious Adverse Events Related to Pump Implantation | 1 Participants |
| Intrahepatic Cholangiocarcinoma | 30-day Postoperative Serious Adverse Events Related to Pump Implantation | 0 Participants |
Secondary
Number of Interventions (Phone Calls) to Assure Patients Attend Followup Appointments.
The number of staff contacts (phone calls) to assure patients keep their followup visits will be tabulated.
Time frame: 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Colorectal Liver Metastases | Number of Interventions (Phone Calls) to Assure Patients Attend Followup Appointments. | 0 Participants |
| Intrahepatic Cholangiocarcinoma | Number of Interventions (Phone Calls) to Assure Patients Attend Followup Appointments. | 0 Participants |
Secondary
Overall Response Rate at 6 Months
RECIST v1.1 will be used to assess overall response rate at 6 months.
Time frame: 6 months
Population: At the 6 month time point for this outcome there were only 14 evaluable participants for response rate due to attrition, death, or sub-RECIST threshold disease.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Colorectal Liver Metastases | Overall Response Rate at 6 Months | Progressive Disease | 4 Participants |
| Colorectal Liver Metastases | Overall Response Rate at 6 Months | Stable Disease | 6 Participants |
| Colorectal Liver Metastases | Overall Response Rate at 6 Months | Partial Response | 1 Participants |
| Intrahepatic Cholangiocarcinoma | Overall Response Rate at 6 Months | Progressive Disease | 2 Participants |
| Intrahepatic Cholangiocarcinoma | Overall Response Rate at 6 Months | Stable Disease | 1 Participants |
| Intrahepatic Cholangiocarcinoma | Overall Response Rate at 6 Months | Partial Response | 0 Participants |
Secondary
Percent of Patients That Require Secondary Intervention in Order to Obtain Primary Pump Function.
Percentage of patients who need secondary intervention (IR embolization, revision of pump or tubing) to achieve primary pump function.
Time frame: Approximately 4 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Colorectal Liver Metastases | Percent of Patients That Require Secondary Intervention in Order to Obtain Primary Pump Function. | 0 Participants |
| Intrahepatic Cholangiocarcinoma | Percent of Patients That Require Secondary Intervention in Order to Obtain Primary Pump Function. | 0 Participants |
Secondary
Percent of Patients Who Are Downstaged and Undergo Surgery
The percent of patients who are downstaged and undergo surgery will be tabulated.
Time frame: 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Colorectal Liver Metastases | Percent of Patients Who Are Downstaged and Undergo Surgery | 7 Participants |
| Intrahepatic Cholangiocarcinoma | Percent of Patients Who Are Downstaged and Undergo Surgery | 0 Participants |
Secondary
Percent of Patients Who Remain on Hepatic Artery Infusion Pump Chemotherapy at 3 Months.
The percentage of patients who remain on pump chemotherapy at 3 months will be tabulated.
Time frame: 3 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Colorectal Liver Metastases | Percent of Patients Who Remain on Hepatic Artery Infusion Pump Chemotherapy at 3 Months. | 14 Participants |
| Intrahepatic Cholangiocarcinoma | Percent of Patients Who Remain on Hepatic Artery Infusion Pump Chemotherapy at 3 Months. | 4 Participants |
Secondary
Percent of Patients Who Remain on Hepatic Artery Infusion Pump Chemotherapy at 6 Months.
The percentage of patients who remain on pump chemotherapy at 6months will be tabulated.
Time frame: 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Colorectal Liver Metastases | Percent of Patients Who Remain on Hepatic Artery Infusion Pump Chemotherapy at 6 Months. | 13 Participants |
| Intrahepatic Cholangiocarcinoma | Percent of Patients Who Remain on Hepatic Artery Infusion Pump Chemotherapy at 6 Months. | 3 Participants |
Secondary
Percent of Screened Patients That Are Declined Due to High Risk of Failure as Determined by the Psychosocial Assessment Tool.
Patients are screen using a psychosocial assessment tool for high risk of hepatic artery pump loss/failure, percent declined will be tabulated.
Time frame: Immediate, determined at screening visit
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Colorectal Liver Metastases | Percent of Screened Patients That Are Declined Due to High Risk of Failure as Determined by the Psychosocial Assessment Tool. | 0 Participants |
| Intrahepatic Cholangiocarcinoma | Percent of Screened Patients That Are Declined Due to High Risk of Failure as Determined by the Psychosocial Assessment Tool. | 0 Participants |
Secondary
Percent Pump Loss Due to Inability to Attend Scheduled Followup Appointments.
Percent of patients that experience pump loss/failure due to inability to attend scheduled followup appointments will be tabulated.
Time frame: Approximately 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Colorectal Liver Metastases | Percent Pump Loss Due to Inability to Attend Scheduled Followup Appointments. | 0 Participants |
| Intrahepatic Cholangiocarcinoma | Percent Pump Loss Due to Inability to Attend Scheduled Followup Appointments. | 0 Participants |