Clinical trial NCT04891289: Gemcitabine and Oxaliplatin Chemotherapy With or Without a Floxuridine and Dexamethasone Pump in People With Cholangiocarcinoma That Cannot Be Removed With Surgery
Official title: A Randomized Phase II Study of Systemic Chemotherapy With or Without HAI FUDR/Dexamethasone in Patients With Unresectable Intrahepatic Cholangiocarcinoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Intrahepatic Cholangiocarcinoma
Keywords: Gemcitabine
Oxaliplatin
Floxuridine
Dexamethasone Pump
20-348
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
First posted: 2021-05-18
Enrollment: 164
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: This is a multi-center, prospective randomized controlled phase II study.
Primary purpose: TREATMENT

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.


Eligibility criteria: 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 randomization.
* 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 or radiation treatment that would yield the same result as surgery 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.

Primary outcomes:
measure: assess progression-free survival (PFS)
timeFrame: 2 years
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: 2 years
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: National Heart, Lung, and Blood Institute (NIH) (Data Collection Only)
state: Maryland
city: Saint Louis
country: United States
facility: Washington University (Data Collection Only)
state: Missouri
city: Basking Ridge
country: United States
facility: Memorial Sloan Kettering Basking Ridge - Limited Protocol Activities
state: New Jersey
city: Middletown
country: United States
facility: Memorial Sloan Kettering Monmouth - Limited Protocol Activities
state: New Jersey
city: Montvale
country: United States
facility: Memorial Sloan Kettering Bergen - Limited Protocol Activities
state: New Jersey
city: Commack
country: United States
facility: Memorial Sloan Kettering Commack - Limited Protocol Activities
state: New York
city: Harrison
country: United States
facility: Memorial Sloan Kettering Westchester - Limited Protocol Activities
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Uniondale
country: United States
facility: Memorial Sloan Kettering Nassau - Limited Protocol Activities
state: New York
city: Durham
country: United States
facility: Duke University (Data Collection Only)
state: North Carolina
city: Rotterdam
country: Netherlands
facility: Erasmus University (Data Collection Only)
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Andrea Cercek, MD
role: PRINCIPAL_INVESTIGATOR
References: