Hepatic Artery Infusion With FOLFOX in Liver Metastasis From Breast Cancer

Pilot Study of Hepatic Arterial Infusion (HAI) With Oxaliplatin, Folinic Acid and 5 Fluorouracil (FOLFOX) in Heavily Pre-Treated Patients With Liver-Predominant Metastasis From Breast Cancer

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.

Study Overview

• Status: Terminated
• Conditions: Metastatic Breast Cancer
• Intervention / Treatment: Drug: HAI with FOLFOX

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.

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Goodyear, Arizona, United States, 85338
      • Western Regional Medical Center Inc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HAI with FOLFOX; Hepatic Artery Infusion with Oxaliplatin, 5FU, and Folinic Acid	Drug: HAI with FOLFOX; HAI with FOLFOX q 3 weeks; Other Names: Hepatic Artery Infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	One year
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.	One year
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.	One year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	one year

Collaborators and Investigators

• Sponsor: Western Regional Medical Center
• Investigators: Principal Investigator: Jiaxin Niu, MD, Western Regional Medical Center

Study record dates

Study Major Dates

• Study Start: December 1, 2012
• Primary Completion (Actual): July 1, 2014
• Study Completion (Actual): July 1, 2014

Study Registration Dates

• First Submitted: June 24, 2013
• First Submitted That Met QC Criteria: September 3, 2013
• First Posted (Estimate): September 9, 2013

Study Record Updates

• Last Update Posted (Actual): February 7, 2018
• Last Update Submitted That Met QC Criteria: January 11, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: 12-20