Phase II Trial Evaluating OS With Therasphere® + 2nd-Line FOLFOX in Pancreatic Liver Mets

Phase 2

Completed

Interventions: Drug: FOLFOX7 (Folinic acid, 5-Fluorouracil, and Oxaliplatin)
Device: TheraSpheres

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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
2nd Line Chemotherapy With Radiotherapy	FOLFOX7 (Folinic acid, 5-Fluorouracil, and Oxaliplatin)	Administration of 2nd line chemotherapy will consist of a modified FOLFOX7 (Folinic acid, 5-Fluorouracil, and Oxaliplatin) will take place at least 2 weeks after the completion of first-line chemotherapy. Generally, second-line chemotherapy is given every two weeks for 6-10 cycles. The goal of treatment with TheraSpheres is to allow a large dose of radiation to be delivered directly to the tumor(s) with less risk of toxic effects from radiation to other parts of the body or to healthy liver tissue.
2nd Line Chemotherapy With Radiotherapy	TheraSpheres	Administration of 2nd line chemotherapy will consist of a modified FOLFOX7 (Folinic acid, 5-Fluorouracil, and Oxaliplatin) will take place at least 2 weeks after the completion of first-line chemotherapy. Generally, second-line chemotherapy is given every two weeks for 6-10 cycles. The goal of treatment with TheraSpheres is to allow a large dose of radiation to be delivered directly to the tumor(s) with less risk of toxic effects from radiation to other parts of the body or to healthy liver tissue.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.