Hepatic Arterial Infusion (HAI) With Floxuridine (FUDR) and Dexamethasone (Dex) Combined With Systemic Gemcitabine and Oxaliplatin in Patients With Unresectable Intrahepatic Cholangiocarcinoma (ICC)

Memorial Sloan Kettering Cancer Center (MSK)

Status and phase: Completed; Phase 2

Conditions: Peripheral Cholangiocarcinoma; Cholangiocellular Carcinoma; Intrahepatic Cholangiocarcinoma; Cholangiolar Carcinoma

Treatments: Other: MRI; Drug: Oxaliplatin; Drug: Floxuridine (FUDR); Other: Research blood draws; Drug: dexamethasone; Drug: Gemcitabine

Study type: Interventional

Funder types: Other

Identifiers

NCT01862315

13-066

Details and patient eligibility

About

The purpose of this study is to use both, liver pump treatment and systemic chemotherapy, to assess the effects this type of treatment has on the patient and the tumor. Liver pump treatment uses a metal pump that is surgically placed in the abdomen and gives chemotherapy directly to the liver. Systemic chemotherapy gives chemotherapy through a vein [intravenously (IV)] and treats the whole body. This type of treatment has been done before and had shown that people with both pump and systemic chemotherapy had improved results. The investigators hope that this combination of treatments improves the response to chemotherapy and reduces the spread of the disease.

Another purpose of this study is to learn the clinical importance of a specific type of MRI scan. The investigators would like to see if this type of MRI will help predict the response to the treatment and see if they could help the physician with their treatment plan. These scans will be done at specific time points.

The last purpose of this study is to learn more about how the tumor interacts with the chemotherapy. This will be done through a biopsy taken during surgery and blood draws at specific time points.

Permission from patients entering the study will be obtained to take normal and tumor liver biopsies at the time of surgery. These samples are voluntary and optional.

Enrollment: 55 patients

Sex: All

Ages: 21+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Age ≥ 21 years
• Histologically confirmed intrahepatic cholangiocarcinoma (also variously reported as peripheral cholangiocarcinoma, cholangiolar carcinoma or cholangiocellular carcinoma) (ICC). Confirmation of the diagnosis at MSKCC or at the enrolling institution must be obtained prior to initiation of protocol therapy.
• Clinical or radiographic evidence of metastatic disease to regional lymph nodes will be allowed, provided it is amenable to resection.
• Radiographically measurable disease. Measurable disease is defined as disease that can be assessed with 2-dimensional measurements on a cross-sectional imaging. Minimum lesion size is 2cm in greatest diameter as per RECIST criteria.
• Disease must be considered unresectable at the time of preoperative evaluation.
• Presence of less than 70% liver involvement by cancer.
• Patients may have failed ablative therapy
• Patient previously treated with systemic chemotherapy will be eligible
• KPS ≥ 60% and be considered candidates for general anesthesia, abdominal exploration and hepatic artery pump placement
• Patients with chronic hepatitis and/or cirrhosis are eligible, but must be Child-Pugh class A
• Patients must be able to read, understand and sign informed consent
• WBC ≥ 2,000 cells/mm3
• Platelet count ≥ 75,000/mm3
• Creatinine ≤ 1.8 mg/dl
• Total bilirubin < 1.5 mg/dl

Exclusion criteria

• Presence of distant metastatic disease. Patients will undergo radiographic evaluation to exclude the possibility of distant metastatic disease. For patients who have undergone pre- or postoperative biopsies that definitively diagnose ICC, the diagnostic studies may be modified at the discretion of the MSKCC Principal Investigator. Clinical or radiographic evidence of metastatic disease to regional lymph nodes will be allowed, provided it is amenable to resection.
• Prior treatment with FUDR
• Prior external beam radiation therapy to the liver
• Diagnosis of sclerosing cholangitis
• Clinical evidence or portal hypertension (ascites, gastroesophageal varices, or portal vein thrombosis) surgically related ascites does not exclude the patient)
• Active infection
• Pregnant or lactating women
• History of other malignancy within the past 3 years (except non-melanoma skin cancer)
• Life expectancy less than 12 weeks
• Inability to comply with study and/or followup procedures
• History of peripheral neuropathy (Note: this does not apply to Cohort 3)

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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55 participants in 3 patient groups

No prior chemo or responded/stable with prior chemo

Experimental group

Description:

All patients receive HAI FUDR (\[0.12 mg/kg/day kg 30\] / pump flow rate)\& dexamethasone ({1 mg/m2/day30} pump flow rate) on Day 1 of each cycle. Chemotherapy with HAI FUDR/Dex will commence no sooner than 14 days postsurgical placement of HAI pump. All patients receive Gemcitabine (800 mg/m2 IV over 30 minutes) \& Oxaliplatin (85 mg/m2 IV over 120 minutes) on Days 1 \& 15 of each cycle, however initiation with systemic chemotherapy will not take place until 4 weeks post-surgery for pump placement, so the first doses of systemic chemotherapy will be given on Cycle 1, Day 15, \& then every 2 weeks thereafter. Clinical MRI examinations of the abdomen \& pelvis are obtained at baseline following surgery, prior to treatment initiation \& 4 weeks after initiation of HAI FUDR. Subsequently, the patient will undergo MRI approximately at months 3, 6 \& 9 thereafter A non-contrast CT of chest, abdomen \& pelvis will also be obtained as part of routine clinical care.

Treatment:

Drug: Gemcitabine

Drug: dexamethasone

Other: Research blood draws

Drug: Floxuridine (FUDR)

Drug: Oxaliplatin

Other: MRI

patients who have failed systemic therapy

Experimental group

Description:

All patients receive HAI FUDR (\[0.12 mg/kg/day kg 30\] / pump flow rate)\& dexamethasone ({1 mg/m2/day 30}/ pump flow rate) on day 1 of each cycle. Chemotherapy with HAI FUDR/Dex will commence no sooner than 14 days postsurgical placement of HAI pump. All patients receive Gemcitabine (800 mg/m2 IV over 30 minutes) \& Oxaliplatin (85 mg/m2 IV over 120 minutes) on Days 1 \& 15 of each cycle, however initiation with systemic chemotherapy will not take place until 4 weeks post-surgery for pump placement, so the first doses of systemic chemotherapy will be given on Cycle 1, Day 15, \& then every 2 weeks thereafter. Clinical MRI examinations of the abdomen \& pelvis are obtained at baseline following surgery, prior to treatment initiation \& 4 weeks after initiation of HAI FUDR. Subsequently, the patient will undergo MRI approximately at months 3, 6 \& 9 thereafter A non-contrast CT of chest, abdomen \& pelvis will also be obtained as part of routine clinical care.

Treatment:

Drug: Gemcitabine

Drug: dexamethasone

Other: Research blood draws

Drug: Floxuridine (FUDR)

Drug: Oxaliplatin

Other: MRI

pts who have had prior oxaliplatin & have existing neuropathy

Experimental group

Description:

All patients receive will receive gemcitabine alone with HAI FUDR/Dex Gemcitabine (800 mg/m2 IV over 30 minutes) alone on Days 1 and 15 of each cycle, however initiation with systemic chemotherapy will not take place until 4 weeks post-surgery for pump placement, so the first doses of systemic chemotherapy will be given on Cycle 1, Day 15, and then every 2 weeks thereafter.

Treatment:

Drug: Gemcitabine

Drug: dexamethasone

Other: Research blood draws

Other: MRI