Metastatic Breast Cancer
Conditions
Brief summary
Deliver oxliplatin and 5-FU via HAI to breast cancer patients with liver-only or liver-predominant metastases who have failed at least one line of systemic chemotherapy in metastatic setting.
Detailed description
In this pilot study, the investigators will deliver oxliplatin and 5-FU via HAI to breast cancer patients with liver-only or liver-predominant metastases who have failed at least one line of systemic chemotherapy in metastatic setting. The investigators hypothesize that HAI chemotherapy will be able to convert some patients to surgical resection candidates, or/and to overcome chemo-resistance of liver metastases to systemic i.v. chemotherapy for some clinically fit, heavily pre-treated patients.
Interventions
DRUGHAI with FOLFOX
HAI with FOLFOX q 3 weeks
Sponsors
Western Regional Medical Center
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
1. Performance status ECOG 0-2 and a life expectancy of \>3 months. 2. Patients were required to have measurable disease in the liver, defined as lesions measuring \>1 cm in largest diameter on spiral-computed tomography (CT) or magnetic resonance imaging (MRI) 3. Histologically confirmed metastatic advanced solid tumors involving the liver, liver replacement less than 70% 4. No bevacizumab (avastin) use within 4 weeks prior to enrollment. 5. Absence of portal vein thrombosis 6. Not a surgical candidate or patients refuge surgery at the time of enrollment 7. Loss of response to at least 1 line of systemic chemotherapy in metastatic setting 8. An asymptomatic extra-hepatic disease is allowed, provided that the extent of the metastatic disease in the liver represented the bulk of the metastatic disease. 9. History of liver-directed therapy is eligible at the investigator's discretion. 10. Adequate renal function with a calculated creatinine clearance greater than 60 mL/min. 11. Hepatic function as follows: Total Bilirubin ≤3 mg/dL, AST ≤5 times upper normal reference value, or ALT ≤ 5 times upper normal reference value. 12. Adequate bone marrow function (ANC ≥1500 cells/uL; PLT ≥ 100,000 cells/uL) before each therapy. 13. At least three weeks from previous immunotherapy, chemotherapy or radiotherapy before being enrolled in this study. 14. All females in childbearing age MUST have a negative serum HCG test unless patients have prior hysterectomy.
Exclusion criteria
1. Clinical or radiographic evidence of moderate amount of ascites. 2. History of cirrhosis with Child-Pugh class B or C. 3. Pregnant or lactating females. 4. Inability to complete informed consent process and adhere to protocol treatment plan and follow-up requirements. 5. Patients receiving any other investigational agents. 6. Patients with bleeding diathesis (clinical bleeding, prothrombin time =/\> 1.5 X upper institutional normal value, INR =/\> 1.5, activated partial thromboplastin time aPTT =/\> 1.5 X upper institutional normal value), active gastric or duodenal ulcer. 7. History of thrombophilia, recurrent DVTs, diagnosis of phospholipid syndrome. 8. Past or current history of malignancy other than breast cancer with the exception of treated non-melanoma skin cancer or carcinoma in situ of the cervix, or other cancers cured by local therapy alone and a DFS ≥5 years. 9. Concurrent severe illness such as active infection, or psychiatric illness/social situations that would limit safety and compliance with study requirements. 10. Patients with clinically significant cardiovascular disease: myocardial infarction or unstable angina within 6 months, New York Heart Association Grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication, unstable angina pectoris, clinically significant peripheral vascular disease 11. Patients have untreated brain metastasis requiring or leptomeningeal metastases.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Determine Response Rate (RR) of HAI With Oxaliplatin/5-FU Every Three Weeks in Heavily Pre-treated Patients With Advanced Breast Cancer With Metastasis to the Liver. | One year | To determine response rate (RR) of HAI with oxaliplatin/5-FU every three weeks in heavily pre-treated patients with advanced breast cancer with metastasis to the liver. |
| Determine Time to Intra-hepatic Progression (TIP) of HAI With Oxaliplatin/5-FU Every Three Weeks in Heavily Pre-treated Patients With Advanced Breast Cancer With Metastasis to the Liver. | One year | To determine time to intra-hepatic progression (TIP) of HAI with oxaliplatin/5-FU every three weeks in heavily pre-treated patients with advanced breast cancer with metastasis to the liver. |
| Extra-hepatic Progression (TEP) of HAI With Oxaliplatin/5-FU | One year | To determine time to extra-hepatic progression (TEP) of HAI with oxaliplatin/5-FU every three weeks in heavily pre-treated patients with advanced breast cancer with metastasis to the liver. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To Document the Toxicity, Tolerability of the Therapy in This Population. | one year | Document the toxicity and tolerability of the therapy using the following CBC with differential, BUN, creatinine, liver function tests,CA 15-3, CA 27.29, Circulating tumor cells (CTCs)and Restaging radiographic studies (MRI or CT liver protocol). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| HAI With FOLFOX Hepatic Artery Infusion with Oxaliplatin, 5FU, and Folinic Acid
HAI with FOLFOX: HAI with FOLFOX q 3 weeks | 0 |
| Total | 0 |
Baseline characteristics
| Characteristic | — |
|---|---|
| Region of Enrollment United States | — participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 0 |
| other Total, other adverse events | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 |
Outcome results
Primary
Determine Response Rate (RR) of HAI With Oxaliplatin/5-FU Every Three Weeks in Heavily Pre-treated Patients With Advanced Breast Cancer With Metastasis to the Liver.
To determine response rate (RR) of HAI with oxaliplatin/5-FU every three weeks in heavily pre-treated patients with advanced breast cancer with metastasis to the liver.
Time frame: One year
Population: Data was not collected
Primary
Determine Time to Intra-hepatic Progression (TIP) of HAI With Oxaliplatin/5-FU Every Three Weeks in Heavily Pre-treated Patients With Advanced Breast Cancer With Metastasis to the Liver.
To determine time to intra-hepatic progression (TIP) of HAI with oxaliplatin/5-FU every three weeks in heavily pre-treated patients with advanced breast cancer with metastasis to the liver.
Time frame: One year
Population: Data was not collected
Primary
Extra-hepatic Progression (TEP) of HAI With Oxaliplatin/5-FU
To determine time to extra-hepatic progression (TEP) of HAI with oxaliplatin/5-FU every three weeks in heavily pre-treated patients with advanced breast cancer with metastasis to the liver.
Time frame: One year
Population: Data was not collected
Secondary
To Document the Toxicity, Tolerability of the Therapy in This Population.
Document the toxicity and tolerability of the therapy using the following CBC with differential, BUN, creatinine, liver function tests,CA 15-3, CA 27.29, Circulating tumor cells (CTCs)and Restaging radiographic studies (MRI or CT liver protocol).
Time frame: one year
Population: Data was not collected