Liver Cancer, Pancreatic Cancer
Conditions
Keywords
liver, pancreas, chemotherapy, radiotherapy
Brief summary
The purpose of this study is to evaluate the safety and impact on survival with treatment with 90-Y glass microspheres in conjunction with leucovorin, 5-fluorouracil (5-FU) and oxaliplatin (FOLFOX) as second-line treatment with in patients gemcitabine-refractory metastatic pancreatic cancer with predominantly liver metastases.
Interventions
DRUGFOLFOX7 (Folinic acid, 5-Fluorouracil, and Oxaliplatin)
The usual treatment if gemcitabine chemotherapy has failed is chemotherapy with a drug combination called FOLFOX (folinic acid, 5-FU and oxaliplatin) given through a vein every 2 weeks for 6-10 cycles. Participants will receive this treatment.
DEVICETheraSpheres
TheraSpheres are a medical device containing yttrium-90 (Y-90), a radioactive material that has been used previously in the treatment of liver tumors. Y-90 is incorporated into very tiny glass beads called microspheres and is injected into the liver through the blood vessels supplying the liver. TheraSpheres have restricted approval from the United States Food and Drug Administration (FDA) for the treatment of hepatocellular liver cancer; but has not yet been approved for the treatment of pancreatic cancer that has spread to the liver.
Sponsors
BTG International Inc.
H. Lee Moffitt Cancer Center and Research Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients must have metastatic pancreatic cancer with predominantly liver metastatic disease (\> 50%), as determined by the principal investigator (PI0 and referring medical oncologist that have progressed on gemcitabine-based chemotherapy. * Patients can have solitary, multifocal unilobar, or bilobar disease. * Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to 2 * No prior radiation or embolization of the liver * Childs-Pugh score ≤ 7 * Lung shunting that predicts lung dose to be ≤ 30 Gy in a single treatment * The effects of TheraSpheres on the developing human fetus at the recommended therapeutic dose are unknown. For this reason and because radioactive spheres are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. * Ability to understand and the willingness to sign a written informed consent document * Adequate baseline hematopoietic function: * total white blood cell count equal to or greater than 3,000/mm\^3 * absolute granulocyte count greater than 1,500/mm\^3 * platelet count equal to or greater than 50,000/mm\^3 * Hemoglobin \> 8.0
Exclusion criteria
* Patients currently receiving any other investigational agents * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements * Pregnant women are excluded from this study because TheraSpheres are radioactive and radiation is a known agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with TheraSpheres, breastfeeding should be discontinued if the mother is treated with TheraSpheres. * Initiation of second-line chemotherapy not consisting of FOLFOX * Patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy. In addition, antiretrovirals are known radiation sensitizers and could dramatically increase the risk of fulminant hepatic failure. Therefore, human immunodeficiency virus(HIV)-positive patients are excluded from the study because of possible lethal side effects. * Bulk disease (tumor volume \> 70% of the target liver volume) * Aspartic transaminase (AST) or alanine transaminase (ALT) \> 5 times upper limit of normal (ULN) * Bilirubin \> 2 mg/dL * Child-Pugh score \> 7 * Tumor volume \> 50% of liver combined with an albumin \< 3 g/dL * Complete occlusion of main portal vein causing portal hypertension
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Median Overall Survival (OS) | Up to 29 months | OS, defined as the time from study enrollment to death from any cause, will be analyzed and summarized with the survival probabilities over time using Kaplan-Meier method. Confidence intervals for the median OS rates at different time points will be constructed when appropriate. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Progression Free Survival (PFS) | Up to 29 months | PFS defined as the time from study enrollment to progression in the liver by modified Response Evaluation Criteria in Solid Tumors (RECIST) or death, whichever occurs first will be analyzed and summarized with the survival probabilities over time using Kaplan-Meier method. Confidence intervals for the median PFS rates at different time points will be constructed when appropriate. |
| Overall Response Rate (ORR) | Up to 29 months | The overall response: ORR = complete response (CR) + partial response (PR). Rate will be summarized using both point estimates and exact confidence intervals based on the binomial distribution by groups. |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled at Moffitt Cancer Center June 2012 through March 2014.
Participants by arm
| Arm | Count |
|---|---|
| 2nd Line Chemotherapy With Radiotherapy Administration of 2nd line chemotherapy consisted of a modified FOLFOX7 (Folinic acid, 5-Fluorouracil, and Oxaliplatin) to take place at least 2 weeks after the completion of first-line chemotherapy. Generally, second-line chemotherapy was to be given every two weeks for 6-10 cycles. | 9 |
| Total | 9 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | 2nd Line Chemotherapy With Radiotherapy |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 5 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants |
| Age, Continuous | 70.44 years |
| Region of Enrollment United States | 9 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 8 / 9 |
| serious Total, serious adverse events | 5 / 9 |
Outcome results
Primary
Median Overall Survival (OS)
OS, defined as the time from study enrollment to death from any cause, will be analyzed and summarized with the survival probabilities over time using Kaplan-Meier method. Confidence intervals for the median OS rates at different time points will be constructed when appropriate.
Time frame: Up to 29 months
Population: All participants evaluable at time of analysis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 2nd Line Chemotherapy With Radiotherapy | Median Overall Survival (OS) | 14.09 months |
Secondary
Overall Response Rate (ORR)
The overall response: ORR = complete response (CR) + partial response (PR). Rate will be summarized using both point estimates and exact confidence intervals based on the binomial distribution by groups.
Time frame: Up to 29 months
Population: All participants evaluable at time of analysis
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 2nd Line Chemotherapy With Radiotherapy | Overall Response Rate (ORR) | Complete Response | 0 Participants |
| 2nd Line Chemotherapy With Radiotherapy | Overall Response Rate (ORR) | Partial Response | 5 Participants |
Secondary
Rate of Progression Free Survival (PFS)
PFS defined as the time from study enrollment to progression in the liver by modified Response Evaluation Criteria in Solid Tumors (RECIST) or death, whichever occurs first will be analyzed and summarized with the survival probabilities over time using Kaplan-Meier method. Confidence intervals for the median PFS rates at different time points will be constructed when appropriate.
Time frame: Up to 29 months
Population: All participants evaluable at time of analysis
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 2nd Line Chemotherapy With Radiotherapy | Rate of Progression Free Survival (PFS) | 3 Participants |