Gemcitabine and Oxaliplatin Chemotherapy With or Without a Floxuridine and Dexamethasone Pump in People With Cholangiocarcinoma That Cannot Be Removed With Surgery

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT04891289

Collaborator

(none)

164

Enrollment

Locations

Arms

35.8

Anticipated Duration (Months)

20.5

Patients Per Site

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will compare the safety and effects of HAI floxuridine and dexamethasone combined with the standard chemotherapy drugs gemcitabine and oxaliplatin (GemOx) with those of GemOx alone in people with untreated cholangiocarcinoma that cannot be removed with surgery. The researchers want to find out whether the study treatment works better than the standard chemotherapy to delay progression of disease. For the study treatment to be considered better than the standard treatment, the study treatment should increase the time until progression of disease by an average of 3 months, compared with the usual approach.

Condition or Disease	Intervention/Treatment	Phase
Intrahepatic Cholangiocarcinoma	Drug: Gemcitabine Drug: Oxaliplatin Drug: Dexamethasone Drug: Floxuridine (FUDR) Device: Implanted Medical Device	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

164 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Intervention Model Description:

This is a multi-center, prospective randomized controlled phase II study.This is a multi-center, prospective randomized controlled phase II study.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Randomized Phase II Study of Systemic Chemotherapy With or Without HAI FUDR/Dexamethasone in Patients With Unresectable Intrahepatic Cholangiocarcinoma

Actual Study Start Date :

May 7, 2021

Anticipated Primary Completion Date :

May 1, 2024

Anticipated Study Completion Date :

May 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: HAI FUDR plus GemOx (Arm 1) Surgical HAI pump placement. 2. HAI FUDR [(0.12 mg/kg/day) x wt (kg) x (20ml) X 0.9) / pump flow rate (1ml/day)] and dexamethasone [1 mg/day * 20] / pump flow rate (1 ml/day) on Day 1 of each cycle. Chemotherapy with HAI FUDR/Dex will commence no sooner than 14 days postsurgical placement of HAI pump. 3. Gemcitabine (800 mg/m2 IV over 30 minutes) and oxaliplatin (85 mg/ m2 IV over 120 minutes on Days 1 and 15 of each cycle; however, for patients in Arm 1, initiation of systemic chemotherapy will not take place until 4 weeks post-surgery for pump placement, so the first dose of systemic chemotherapy will be given on Cycle 1, Day 15, and then every 2 weeks thereafter.	Drug: Gemcitabine See arm for details. Drug: Oxaliplatin See arm for details. Drug: Dexamethasone See arm for details. Drug: Floxuridine (FUDR) See arm for details. Device: Implanted Medical Device Implanted hepatic arterial infusion pump by surgical oncology, to deliver HAI therapy
Active Comparator: GemOx alone (Arm 2) Gemcitabine (800 mg/m2 IV over 30 minutes) and oxaliplatin (85 mg/m2 IV over approximately 120 minutes) on Days 1 and 15 of each 28-day cycle.For patients in Arm 2, systemic therapy will be administered on Days 1 and Day 15 of each Cycle on a 28-day cycle basis, compromised of Gemcitabine and Oxaliplatin. If a patient randomized to Arm 2 has intrahepatic progression on any follow-up scan during study treatment, that patient will be eligible to crossover to Arm 1 and commence to pump placement surgery and HAI FUDR treatment. Patients with any extrahepatic progression will not be eligible to utilize the crossover arm. Arm 2 patients will have 28 days from date of the scan showing intrahepatic progression to proceed to the crossover arm.	Drug: Gemcitabine See arm for details. Drug: Oxaliplatin See arm for details.

Arm

Intervention/Treatment

Experimental: HAI FUDR plus GemOx (Arm 1)

Surgical HAI pump placement. 2. HAI FUDR [(0.12 mg/kg/day) x wt (kg) x (20ml) X 0.9) / pump flow rate (1ml/day)] and dexamethasone [1 mg/day * 20] / pump flow rate (1 ml/day) on Day 1 of each cycle. Chemotherapy with HAI FUDR/Dex will commence no sooner than 14 days postsurgical placement of HAI pump. 3. Gemcitabine (800 mg/m2 IV over 30 minutes) and oxaliplatin (85 mg/ m2 IV over 120 minutes on Days 1 and 15 of each cycle; however, for patients in Arm 1, initiation of systemic chemotherapy will not take place until 4 weeks post-surgery for pump placement, so the first dose of systemic chemotherapy will be given on Cycle 1, Day 15, and then every 2 weeks thereafter.

Drug: Gemcitabine

See arm for details.

Drug: Oxaliplatin

See arm for details.

Drug: Dexamethasone

See arm for details.

Drug: Floxuridine (FUDR)

See arm for details.

Device: Implanted Medical Device

Implanted hepatic arterial infusion pump by surgical oncology, to deliver HAI therapy

Active Comparator: GemOx alone (Arm 2)

Gemcitabine (800 mg/m2 IV over 30 minutes) and oxaliplatin (85 mg/m2 IV over approximately 120 minutes) on Days 1 and 15 of each 28-day cycle.For patients in Arm 2, systemic therapy will be administered on Days 1 and Day 15 of each Cycle on a 28-day cycle basis, compromised of Gemcitabine and Oxaliplatin. If a patient randomized to Arm 2 has intrahepatic progression on any follow-up scan during study treatment, that patient will be eligible to crossover to Arm 1 and commence to pump placement surgery and HAI FUDR treatment. Patients with any extrahepatic progression will not be eligible to utilize the crossover arm. Arm 2 patients will have 28 days from date of the scan showing intrahepatic progression to proceed to the crossover arm.

Drug: Gemcitabine

See arm for details.

Drug: Oxaliplatin

See arm for details.

Outcome Measures

Primary Outcome Measures

assess progression-free survival (PFS) [2 years]
will be done using RECIST (version 1.1).

Secondary Outcome Measures

Overall survival (OS) [2 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age ≥18 years
ECOG 0-1
Histologically confirmed intrahepatic cholangiocarcinoma (also variously reported as peripheral cholangiocarcinoma, cholangiolar carcinoma or cholangiocellular carcinoma) (IHC). 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 confined to the liver. Note: presence of regional (porta hepatis) lymph node metastases will be allowed, provided they are amenable to resection. (Note: If peritoneal or other extrahepatic disease is found at time of pump placement, the pump will not be implanted. The patient will be removed from study, deemed nonevaluable and will not count toward the overall study accrual.)
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 2 cm in greatest diameter as per RECIST criteria.
Disease must be considered unresectable at the time of preoperative evaluation.*
Considered candidate 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.
WBC ≥ 2,000/mcL , ANC ≥ 1000/mcL
Platelet count ≥ 75,000/mcL
Creatinine ≤ 1.8 mg/dL
Total bilirubin < 1.5 mg/dL
Hgb > 7 g/dL The % involvement of the liver will be determined by radiologists after review of imaging

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 post-operative biopsies that definitively diagnose IHC, 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.
Patients previously treated with systemic chemotherapy for IHC will be non-eligible.
Prior treatment with FUDR.
Prior external beam radiation therapy to the liver.
Prior ablative 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 within one week prior to HAI placement.
Pregnant or lactating women.
History of other malignancy within the past 3 years except with early stage/localized cancer that was surgically resected within the past 3 years.
Life expectancy <12 weeks.
Inability to comply with study and/or follow-up procedures.
History of peripheral neuropathy. There is no exclusion of patients based on sex, ethnicity or race. For these reasons, the study results are expected to be generalizable to the Medicare beneficiary population.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memorial Sloan Kettering Basking Ridge - Limited Protocol Activities	Basking Ridge	New Jersey	United States	07920
2	Memorial Sloan Kettering Monmouth - Limited Protocol Activities	Middletown	New Jersey	United States	07748
3	Memorial Sloan Kettering Bergen - Limited Protocol Activities	Montvale	New Jersey	United States	07645
4	Memorial Sloan Kettering Commack - Limited Protocol Activities	Commack	New York	United States	11725
5	Memoral Sloan Kettering Westchester - Limited Protocol Activities	Harrison	New York	United States	10604
6	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
7	Memorial Sloan Kettering Nassau - Limited Protocol Activities	Uniondale	New York	United States	11553
8	Duke University (Data Collection Only)	Durham	North Carolina	United States	27710