Cancer, Hepatic Injury
Conditions
Brief summary
The purposes of this study are to make Omegaven® available to cancer patients with liver disease and to determine if Omegaven® can improve or prevent further liver disease. The study will also look at the effects Omegaven® has on immune function.
Detailed description
This compassionate use study will include patients with advanced cancer requiring PN for long-term nutrition support who have developed PN-induced hepatic injury or who have existing hepatic dysfunction. Therapy with Omegaven will be provided at an initial dose of 0.1 g/kg body weight (1ml/kg) and increased to 0.2 g/kg body weight (2ml/kg) on day 2 or 3 of treatment. For patients \> 120% ideal body weight, adjusted body weight will be used. The infusion rate will not exceed 0.5mL Omegaven/kg body weight/hr (corresponding to 0.05g fish oil/kg/hr). Omegaven will be co-administered via a y-site infusion, with containers being changed every 12 hours. The patient may receive other lipids to meet Essential Fatty Acid (EFA) and/or additional calorie needs. Patients will receive the initial infusion of PN containing Omegaven at Midwestern Regional Medical Center (MRMC) in the infusion center to observe for adverse reactions. If an adverse reaction is observed, IV steroids & benadryl will be administered & Omegaven will be discontinued. Patients will continue to receive infusions at CTCA for the first 2 to 3 days of dosing. After tolerance is established, patients will receive treatment at home with Coram. All study patients will have a Screening Visit; Day 1, Day 2 and Day 3 visits; and weekly visits for one month (see Table 2).
Interventions
DRUGOmegaven
initial dose of 0.1 g/kg body weight (1ml/kg) and increased to 0.2 g/kg body weight (2ml/kg) on day 2 or 3 of treatment. The infusion rate will not exceed 0.5mL Omegaven/kg body weight/hr (corresponding to 0.05g fish oil/kg/hr). Patients will receive the initial infusion of PN containing Omegaven at Midwestern Regional Medical Center (MRMC) in the infusion center to observe for adverse reactions. Patients will continue to receive infusions at MRMC for the first 2 to 3 days of dosing. After tolerance is established, patients will receive treatment at home. All study patients will have a Screening Visit; Day 1, Day 2 and Day 3 visits; and weekly visits for one month.
Sponsors
Midwestern Regional Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Male or Female; ages 18 to 80 years old 2. Receiving treatment at Cancer Treatment Centers of America 3. Receiving PN (either in the infusion center or at home) 4. Have existing hepatic dysfunction defined as Elevation of \> 3x the normal level of one or more of the following:Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), or Alanine Aminotransferase ALT) and/or Bilirubin \> 2 mg/dl in the absence of biliary obstruction 5. Able to provide informed written consent
Exclusion criteria
1. Hypertriglyceridemia (triglycerides \[TG\] \> 400) 2. Allergy to fish or egg protein 3. Currently on therapeutic doses of Coumadin, heparin, or low molecular eight heparin 4. Hemodynamically unstable 5. Bilirubin \> 5 mg/dL 6. Documented liver metastases 7. Unstable diabetes with known diabetic ketoacidosis within 7 days of screening 8. Recent cardiac infarction (within 6 months) and taking plavix 9. Severe hemorrhagic disorders 10. Current anticoagulation therapy for deep venous thromboembolism or pulmonary embolism 11. Active sepsis 12. Undefined coma status 13. In patients with abnormal kidney function, renal insufficiency with calculated creatinine clearance \< 30 mL/min 14. Pregnancy or lactation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Experiencing Adverse Events | Assessed at day 1, 2, 3, and weekly therafter, up to 4 weeks. | The number of patients reporting or experiencing adverse effects will be reported. |
| Average Improvement in AST | Assessed at day 1, 2, 3, and weekly therafter, up to 4 weeks. | Lab values will be summarized at b aselin4e and as change from baseline to worst follow-up value. |
| Average Improvement in ALT | Assessed at day 1, 2, 3, and weekly therafter, up to 4 weeks. | Laboratory values will be summarized at baseline and as change from baseline to worst follow-up value |
| Maximum Conjugated Bilirubin | Assessed at day 1, 2, 3, and weekly therafter, up to 4 weeks. | Highest detected lab values will be summarized between baseline and end of study participation. |
| Average Change in Alkaline Phosphatase | Assessed at day 1, 2, 3, and weekly therafter, up to 4 weeks. | lab values will be summarized at baseline and as change from baseline to worst follow-up value. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Omegaven (Compassionate Use) This is a compassionate use study. All participants will receive intravenous Omegaven (10% fish oil emulsion) with parenteral nutrition for 4 weeks.
Omegaven: initial dose of 0.1 g/kg body weight (1ml/kg) and increased to 0.2 g/kg body weight (2ml/kg) on day 2 or 3 of treatment. The infusion rate will not exceed 0.5mL Omegaven/kg body weight/hr (corresponding to 0.05g fish oil/kg/hr). Patients will receive the initial infusion of PN containing Omegaven at Midwestern Regional Medical Center (MRMC) in the infusion center to observe for adverse reactions. Patients will continue to receive infusions at MRMC for the first 2 to 3 days of dosing. After tolerance is established, patients will receive treatment at home. All study patients will have a Screening Visit; Day 1, Day 2 and Day 3 visits; and weekly visits for one month. | 12 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 1 |
Baseline characteristics
| Characteristic | Omegaven (Compassionate Use) | — |
|---|---|---|
| Age, Categorical <=18 years | 0 Participants | — |
| Age, Categorical >=65 years | 0 Participants | — |
| Age, Categorical Between 18 and 65 years | 12 Participants | — |
| Age, Continuous | 58 Years STANDARD_DEVIATION 10.2 | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment United States | 12 Participants | — |
| Sex: Female, Male Female | 9 Participants | — |
| Sex: Female, Male Male | 3 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 11 |
| other Total, other adverse events | 1 / 11 |
| serious Total, serious adverse events | 0 / 11 |
Outcome results
Primary
Average Change in Alkaline Phosphatase
lab values will be summarized at baseline and as change from baseline to worst follow-up value.
Time frame: Assessed at day 1, 2, 3, and weekly therafter, up to 4 weeks.
Population: Average Improvement in Alkaline Phosphatase
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Omegaven (Compassionate Use) | Average Change in Alkaline Phosphatase | Baseline | 457.6 U/L |
| Omegaven (Compassionate Use) | Average Change in Alkaline Phosphatase | 4 Week Nadir | 360.4 U/L |
p-value: 0.07Wilcoxon (Mann-Whitney)
Primary
Average Improvement in ALT
Laboratory values will be summarized at baseline and as change from baseline to worst follow-up value
Time frame: Assessed at day 1, 2, 3, and weekly therafter, up to 4 weeks.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Omegaven (Compassionate Use) | Average Improvement in ALT | Baseline | 133.6 U/L |
| Omegaven (Compassionate Use) | Average Improvement in ALT | 4 Weeks Nadir | 101.4 U/L |
p-value: 0.48Wilcoxon (Mann-Whitney)
Primary
Average Improvement in AST
Lab values will be summarized at b aselin4e and as change from baseline to worst follow-up value.
Time frame: Assessed at day 1, 2, 3, and weekly therafter, up to 4 weeks.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Omegaven (Compassionate Use) | Average Improvement in AST | Baseline | 88.7 U/L |
| Omegaven (Compassionate Use) | Average Improvement in AST | 4 Weeks Nadir | 69.9 U/L |
p-value: 0.53Wilcoxon (Mann-Whitney)
Primary
Maximum Conjugated Bilirubin
Highest detected lab values will be summarized between baseline and end of study participation.
Time frame: Assessed at day 1, 2, 3, and weekly therafter, up to 4 weeks.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Omegaven (Compassionate Use) | Maximum Conjugated Bilirubin | 1.0 mg/dl | Standard Deviation 0.1 |
Primary
Number of Patients Experiencing Adverse Events
The number of patients reporting or experiencing adverse effects will be reported.
Time frame: Assessed at day 1, 2, 3, and weekly therafter, up to 4 weeks.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Omegaven (Compassionate Use) | Number of Patients Experiencing Adverse Events | 1 Participants |