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

Primary Purpose

Intrahepatic Cholangiocarcinoma

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Gemcitabine
Oxaliplatin
Dexamethasone
Floxuridine (FUDR)
Implanted Medical Device
Sponsored by
Memorial Sloan Kettering Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Intrahepatic Cholangiocarcinoma focused on measuring Gemcitabine, Oxaliplatin, Floxuridine, Dexamethasone Pump, 20-348

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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 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 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.

Sites / Locations

  • National Heart, Lung, and Blood Institute (NIH) (Data Collection Only)Recruiting
  • Washington University (Data Collection Only)Recruiting
  • Memorial Sloan Kettering Basking Ridge - Limited Protocol ActivitiesRecruiting
  • Memorial Sloan Kettering Monmouth - Limited Protocol ActivitiesRecruiting
  • Memorial Sloan Kettering Bergen - Limited Protocol ActivitiesRecruiting
  • Memorial Sloan Kettering Commack - Limited Protocol ActivitiesRecruiting
  • Memorial Sloan Kettering Westchester - Limited Protocol ActivitiesRecruiting
  • Memorial Sloan Kettering Cancer CenterRecruiting
  • Memorial Sloan Kettering Nassau - Limited Protocol ActivitiesRecruiting
  • Duke University (Data Collection Only)Recruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

HAI FUDR plus GemOx (Arm 1)

GemOx alone (Arm 2)

Arm Description

Surgical HAI pump placement. 2. HAI FUDR [(0.12 mg/kg/day) x wt (kg) x (30ml) / pump flow rate ] and dexamethasone [1 mg/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. 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.

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Overall survival (OS)

Full Information

First Posted
May 7, 2021
Last Updated
July 19, 2023
Sponsor
Memorial Sloan Kettering Cancer Center
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1. Study Identification

Unique Protocol Identification Number
NCT04891289
Brief Title
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

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 7, 2021 (Actual)
Primary Completion Date
May 2025 (Anticipated)
Study Completion Date
May 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Memorial Sloan Kettering Cancer Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Intrahepatic Cholangiocarcinoma
Keywords
Gemcitabine, Oxaliplatin, Floxuridine, Dexamethasone Pump, 20-348

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Model Description
This is a multi-center, prospective randomized controlled phase II study.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
164 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
HAI FUDR plus GemOx (Arm 1)
Arm Type
Experimental
Arm Description
Surgical HAI pump placement. 2. HAI FUDR [(0.12 mg/kg/day) x wt (kg) x (30ml) / pump flow rate ] and dexamethasone [1 mg/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. 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.
Arm Title
GemOx alone (Arm 2)
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Gemcitabine
Intervention Description
See arm for details.
Intervention Type
Drug
Intervention Name(s)
Oxaliplatin
Intervention Description
See arm for details.
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Intervention Description
See arm for details.
Intervention Type
Drug
Intervention Name(s)
Floxuridine (FUDR)
Intervention Description
See arm for details.
Intervention Type
Device
Intervention Name(s)
Implanted Medical Device
Intervention Description
Implanted hepatic arterial infusion pump by surgical oncology, to deliver HAI therapy
Primary Outcome Measure Information:
Title
assess progression-free survival (PFS)
Description
will be done using RECIST (version 1.1).
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Overall survival (OS)
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Andrea Cercek, MD
Phone
646-888-4189
Email
cerceka@mskcc.org
First Name & Middle Initial & Last Name or Official Title & Degree
William Jarnagin, MD
Phone
212-639-7601
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andrea Cercek, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
National Heart, Lung, and Blood Institute (NIH) (Data Collection Only)
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20824
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jonathan Hernandez, MD
Phone
240-858-7006
Facility Name
Washington University (Data Collection Only)
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
William Chapman, MD
Phone
314-362-2538
Facility Name
Memorial Sloan Kettering Basking Ridge - Limited Protocol Activities
City
Basking Ridge
State/Province
New Jersey
ZIP/Postal Code
07920
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Andrea Cercek, MD
Phone
646-888-4189
First Name & Middle Initial & Last Name & Degree
Andrea Cercek, MD
Facility Name
Memorial Sloan Kettering Monmouth - Limited Protocol Activities
City
Middletown
State/Province
New Jersey
ZIP/Postal Code
07748
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Andrea Cercek, MD
Phone
646-888-4189
Facility Name
Memorial Sloan Kettering Bergen - Limited Protocol Activities
City
Montvale
State/Province
New Jersey
ZIP/Postal Code
07645
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Andrea Cercek, MD
Phone
646-888-4189
Facility Name
Memorial Sloan Kettering Commack - Limited Protocol Activities
City
Commack
State/Province
New York
ZIP/Postal Code
11725
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Andrea Cercek, MD
Phone
646-888-4189
First Name & Middle Initial & Last Name & Degree
Andera Cercek, MD
Facility Name
Memorial Sloan Kettering Westchester - Limited Protocol Activities
City
Harrison
State/Province
New York
ZIP/Postal Code
10604
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Andrea Cercek, MD
Phone
646-888-4189
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Andrew Cercek, MD
Phone
646-888-4189
Facility Name
Memorial Sloan Kettering Nassau - Limited Protocol Activities
City
Uniondale
State/Province
New York
ZIP/Postal Code
11553
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Andrea Cercek, MD
Phone
646-888-4189
Facility Name
Duke University (Data Collection Only)
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Michael Lidsky, MD
Phone
919-660-9673

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.
Links:
URL
http://www.mskcc.org/mskcc/html/44.cfm
Description
Memorial Sloan Kettering Cancer Center

Learn more about this trial

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

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