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Hepatic Arterial Infusion With Floxuridine and Dexamethasone Combination With Chemotherapy With/Without Bevacizumab for Hepatic Metastases From Colorectal Cancer

Primary Purpose

Hepatic Metastases, Colon Cancer, Rectal Cancer

Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Bevacizumab HAI plus systemic chemotherapy
HAI plus systemic chemotherapy
Sponsored by
Memorial Sloan Kettering Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatic Metastases focused on measuring BEVACIZUMAB (AVASTIN), DEXAMETHASONE, FLOXURIDINE, FLUOROURACIL, IRINOTECAN (CPT-11) CAMPTOSAR, LEUCOVORIN, OXALIPLATIN, Colon, Rectal, 04-086, Adjuvant postoperative chemo for CLM

Eligibility Criteria

19 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: History of histologically confirmed colorectal adenocarcinoma metastatic to the liver with no clinical or radiographic evidence of extrahepatic disease. Confirmation of diagnosis must be performed at MSKCC. Potentially completely resectable hepatic metastases without current evidence of other metastatic disease. Abdominal and pelvic CT scans and chest CT or x-ray within 6 weeks prior to registration. (MRI of abdomen may be substituted for CT of abdomen.) Lab values within 14 days prior to registration: WBC ≥ 3.0 K/uL ANC > 1.5 K/uL Platelets ≥ 75 K/uL Total bilirubin < 1.5 mg/dL INR < 1.5 Creatinine < 2.0 mg/dL HGB ≥ 9 gm/dL Prior chemotherapy is acceptable if last dose given ≥ 3 weeks prior to registration to this study. [Note: no chemotherapy to be given after resection of liver lesions prior to treatment on this study.] KPS ≥ 70% Signed informed consent Patient age must be >18 Exclusion Criteria: Prior radiation to the liver. (Prior radiation therapy to the pelvis is acceptable if completed at least 4 weeks prior to registration.) Active infection, ascites, hepatic encephalopathy. Prior treatment with HAI FUDR. Female patients who are pregnant or lactating. Subjects discovered to have ≥1+ proteinuria at baseline will undergo a 24-hour urine collection, which must be an adequate collection and must demonstrate <1 g of protein/24 hours to allow participation in this study. Patients may not be receiving any other investigational agents Patients with known brain metastases that would confound the evaluation of neurologic and other adverse events will be excluded. Patients with history of primary CNS tumors, seizures not well-controlled with standard medical therapy, or history of stroke will also be excluded. History of allergic reactions attributed to compounds of similar chemical or biologic composition to bevacizumab. Serious or non-healing active wound, ulcer, or bone fracture Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to Day 1 of protocol treatment. (Surgery performed to resect metastatic lesions and place pump will not exclude patient from protocol; Day 1 of protocol treatment will take place no sooner than 28 days after surgery.) Current or recent use of a thrombolytic agent. Chronic daily treatment with aspirin (> 325 mg/d) or nonsteroidal anti-inflammatory medications known to inhibit the platelet function. Presence of bleeding diathesis or coagulopathy. History of serious systemic disease, including myocardial infarction within the last 12 months, uncontrolled hypertension (blood pressure of > 160/110 mmHg on medication), unstable angina within the last 12 months, New York Heart Association (NYHA) Grade II or greater congestive heart failure (see Appendix C), unstable symptomatic arrhythmia requiring medication (subjects with chronic atrial arrhythmia, i. e. atrial fibrillation or paroxysmal supraventricular tachycardia are eligible), or peripheral vascular disease (Grade II or greater). Patients with a history of stroke or transient ischemic attack. Presence of central nervous system or brain metastases. Patients who have a diagnosis of Gilbert's disease.

Sites / Locations

  • Memorial Sloan Kettering Basking Ridge (Follow Up Only)
  • Memorial Sloan Kettering Cancer Commack (Follow Up Only)
  • Memorial Sloan Kettering Westchester (Follow Up Only)
  • Memorial Sloan Kettering Cancer Center
  • Memorial Sloan Kettering Nassau (Follow Up Only)

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

1

2

Arm Description

Bevacizumab in addition to HAI plus systemic chemotherapy

HAI plus systemic chemotherapy alone

Outcomes

Primary Outcome Measures

To determine whether the addition of concurrent intravenous bevacizumab to HAI plus systemic chemotherapy increases the time to progression in patients with completely resected hepatic metastases from colorectal cancer

Secondary Outcome Measures

To assess toxicity
To determine survival
To assess the expression pattern of VEGFR1, VEGFR2 (angiogenesis), and VEGFR3 (lymphangiogenesis) and their cognate ligands (VEGF-A, VEGF-C, VEGF-D), and correlate with patient progression and survival following
To compare plasma levels of VEGF-A, VEGF-C, VEGF-D, and CD133+ VEGFR2+ circulating endothelial progenitors

Full Information

First Posted
September 12, 2005
Last Updated
April 26, 2023
Sponsor
Memorial Sloan Kettering Cancer Center
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1. Study Identification

Unique Protocol Identification Number
NCT00200200
Brief Title
Hepatic Arterial Infusion With Floxuridine and Dexamethasone Combination With Chemotherapy With/Without Bevacizumab for Hepatic Metastases From Colorectal Cancer
Official Title
Randomized Ph II Study of Hepatic Arterial Infusion With Floxuridine and Dexamethasone Combination With IV Systemic Chemo With/Without Bevacizumab (mAB to Vascular Endothelial Growth Factor-A) in Patients With Resected Hepatic Metastases From Colorectal Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
November 19, 2004 (undefined)
Primary Completion Date
November 2024 (Anticipated)
Study Completion Date
November 2024 (Anticipated)

3. Sponsor/Collaborators

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

4. Oversight

5. Study Description

Brief Summary
The purpose of this study is to determine whether the addition of bevacizumab, to hepatic arterial therapy with floxuridine (FUDR) and dexamethasone (Dex) (regional chemotherapy), and either oxaliplatin or CPT-11, plus 5-fluorouracil and leucovorin (systemic chemotherapy) will increase disease free survival in patients who have undergone liver resection. The patient will be randomized (a computer generated decision as in the flip of a coin) to receive, or not to receive bevacizumab in addition to regional and systemic chemotherapy.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatic Metastases, Colon Cancer, Rectal Cancer
Keywords
BEVACIZUMAB (AVASTIN), DEXAMETHASONE, FLOXURIDINE, FLUOROURACIL, IRINOTECAN (CPT-11) CAMPTOSAR, LEUCOVORIN, OXALIPLATIN, Colon, Rectal, 04-086, Adjuvant postoperative chemo for CLM

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
73 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Active Comparator
Arm Description
Bevacizumab in addition to HAI plus systemic chemotherapy
Arm Title
2
Arm Type
Experimental
Arm Description
HAI plus systemic chemotherapy alone
Intervention Type
Drug
Intervention Name(s)
Bevacizumab HAI plus systemic chemotherapy
Intervention Description
Oxaliplatin (mg/m2) IV, over 2 hours, 5 FU (mg/m2) continuous infusion, over two days, leucovorin (mg/m2) IV, over 2 hours
Intervention Type
Drug
Intervention Name(s)
HAI plus systemic chemotherapy
Intervention Description
Irinotecan (mg/m2) IV, over 30 minutes, 5 FU (mg/m2) continuous infusion over two days, leucovorin (mg/m2) IV, over 30 minutes
Primary Outcome Measure Information:
Title
To determine whether the addition of concurrent intravenous bevacizumab to HAI plus systemic chemotherapy increases the time to progression in patients with completely resected hepatic metastases from colorectal cancer
Time Frame
7.5 months
Secondary Outcome Measure Information:
Title
To assess toxicity
Time Frame
7.5 months
Title
To determine survival
Time Frame
2 years
Title
To assess the expression pattern of VEGFR1, VEGFR2 (angiogenesis), and VEGFR3 (lymphangiogenesis) and their cognate ligands (VEGF-A, VEGF-C, VEGF-D), and correlate with patient progression and survival following
Time Frame
2 years
Title
To compare plasma levels of VEGF-A, VEGF-C, VEGF-D, and CD133+ VEGFR2+ circulating endothelial progenitors
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
19 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: History of histologically confirmed colorectal adenocarcinoma metastatic to the liver with no clinical or radiographic evidence of extrahepatic disease. Confirmation of diagnosis must be performed at MSKCC. Potentially completely resectable hepatic metastases without current evidence of other metastatic disease. Abdominal and pelvic CT scans and chest CT or x-ray within 6 weeks prior to registration. (MRI of abdomen may be substituted for CT of abdomen.) Lab values within 14 days prior to registration: WBC ≥ 3.0 K/uL ANC > 1.5 K/uL Platelets ≥ 75 K/uL Total bilirubin < 1.5 mg/dL INR < 1.5 Creatinine < 2.0 mg/dL HGB ≥ 9 gm/dL Prior chemotherapy is acceptable if last dose given ≥ 3 weeks prior to registration to this study. [Note: no chemotherapy to be given after resection of liver lesions prior to treatment on this study.] KPS ≥ 70% Signed informed consent Patient age must be >18 Exclusion Criteria: Prior radiation to the liver. (Prior radiation therapy to the pelvis is acceptable if completed at least 4 weeks prior to registration.) Active infection, ascites, hepatic encephalopathy. Prior treatment with HAI FUDR. Female patients who are pregnant or lactating. Subjects discovered to have ≥1+ proteinuria at baseline will undergo a 24-hour urine collection, which must be an adequate collection and must demonstrate <1 g of protein/24 hours to allow participation in this study. Patients may not be receiving any other investigational agents Patients with known brain metastases that would confound the evaluation of neurologic and other adverse events will be excluded. Patients with history of primary CNS tumors, seizures not well-controlled with standard medical therapy, or history of stroke will also be excluded. History of allergic reactions attributed to compounds of similar chemical or biologic composition to bevacizumab. Serious or non-healing active wound, ulcer, or bone fracture Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to Day 1 of protocol treatment. (Surgery performed to resect metastatic lesions and place pump will not exclude patient from protocol; Day 1 of protocol treatment will take place no sooner than 28 days after surgery.) Current or recent use of a thrombolytic agent. Chronic daily treatment with aspirin (> 325 mg/d) or nonsteroidal anti-inflammatory medications known to inhibit the platelet function. Presence of bleeding diathesis or coagulopathy. History of serious systemic disease, including myocardial infarction within the last 12 months, uncontrolled hypertension (blood pressure of > 160/110 mmHg on medication), unstable angina within the last 12 months, New York Heart Association (NYHA) Grade II or greater congestive heart failure (see Appendix C), unstable symptomatic arrhythmia requiring medication (subjects with chronic atrial arrhythmia, i. e. atrial fibrillation or paroxysmal supraventricular tachycardia are eligible), or peripheral vascular disease (Grade II or greater). Patients with a history of stroke or transient ischemic attack. Presence of central nervous system or brain metastases. Patients who have a diagnosis of Gilbert's disease.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nancy Kemeny, M.D
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Memorial Sloan Kettering Basking Ridge (Follow Up Only)
City
Basking Ridge
State/Province
New Jersey
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Commack (Follow Up Only)
City
Commack
State/Province
New York
ZIP/Postal Code
11725
Country
United States
Facility Name
Memorial Sloan Kettering Westchester (Follow Up Only)
City
Harrison
State/Province
New York
ZIP/Postal Code
10604
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Memorial Sloan Kettering Nassau (Follow Up Only)
City
Uniondale
State/Province
New York
ZIP/Postal Code
11553
Country
United States

12. IPD Sharing Statement

Links:
URL
http://www.mskcc.org
Description
Memorial Sloan-Kettering Cancer Center

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Hepatic Arterial Infusion With Floxuridine and Dexamethasone Combination With Chemotherapy With/Without Bevacizumab for Hepatic Metastases From Colorectal Cancer

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