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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Mount Sinai Hospital, New York
Mount Sinai School of Medicine
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT00200200
First received: September 12, 2005
Last updated: November 21, 2013
Last verified: November 2013
  Purpose

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.


Condition Intervention Phase
Hepatic Metastases
Colon Cancer
Rectal Cancer
Drug: Bevacizumab HAI plus systemic chemotherapy
Drug: HAI plus systemic chemotherapy
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

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 [ Time Frame: 7.5 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To assess toxicity [ Time Frame: 7.5 months ] [ Designated as safety issue: No ]
  • To determine survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • To compare plasma levels of VEGF-A, VEGF-C, VEGF-D, and CD133+ VEGFR2+ circulating endothelial progenitors [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Enrollment: 73
Study Start Date: November 2004
Estimated Study Completion Date: November 2014
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Bevacizumab in addition to HAI plus systemic chemotherapy
Drug: Bevacizumab HAI plus systemic chemotherapy
Oxaliplatin (mg/m2) IV, over 2 hours, 5 FU (mg/m2) continuous infusion, over two days, leucovorin (mg/m2) IV, over 2 hours
Experimental: 2
HAI plus systemic chemotherapy alone
Drug: HAI plus systemic chemotherapy
Irinotecan (mg/m2) IV, over 30 minutes, 5 FU (mg/m2) continuous infusion over two days, leucovorin (mg/m2) IV, over 30 minutes

  Eligibility

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00200200

Locations
United States, New Jersey
Memoral Sloan Kettering Cancer Center
Basking Ridge, New Jersey, United States
United States, New York
Memorial Sloan-Kettering Cancer Center @ Suffolk
Commack, New York, United States, 11725
Memorial Sloan-Kettering Cancer Center 1275 York Avenue
New York, New York, United States, 10021
Memorial Sloan-Kettering Cancer Center at Mercy Medical Center
Rockville Centre, New York, United States, 11570
Memoral Sloan Kettering Cancer Center at Phelps
Sleepy Hollow, New York, United States, 10591
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Mount Sinai Hospital, New York
Mount Sinai School of Medicine
Investigators
Principal Investigator: Nancy Kemeny, M.D Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT00200200     History of Changes
Obsolete Identifiers: NCT00263848
Other Study ID Numbers: 04-086
Study First Received: September 12, 2005
Last Updated: November 21, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Memorial Sloan-Kettering Cancer Center:
BEVACIZUMAB (AVASTIN)
DEXAMETHASONE
FLOXURIDINE
FLUOROURACIL
IRINOTECAN (CPT-11) CAMPTOSAR
LEUCOVORIN
OXALIPLATIN
Colon
Rectal
04-086
Adjuvant postoperative chemo for CLM

Additional relevant MeSH terms:
Colorectal Neoplasms
Neoplasm Metastasis
Liver Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Neoplastic Processes
Pathologic Processes
Liver Diseases
Bevacizumab
Dexamethasone
Floxuridine
Dexamethasone acetate
Dexamethasone 21-phosphate
BB 1101
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 18, 2014