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

Sponsor
Memorial Sloan Kettering Cancer Center (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT00200200
Collaborator
(none)
73
5
2
227.4
14.6
0.1

Study Details

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Bevacizumab HAI plus systemic chemotherapy
  • Drug: HAI plus systemic chemotherapy
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
73 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (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
Study Start Date :
Nov 19, 2004
Anticipated Primary Completion Date :
Nov 1, 2023
Anticipated Study Completion Date :
Nov 1, 2023

Arms and Interventions

Arm Intervention/Treatment
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

Outcome Measures

Primary Outcome Measures

  1. 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 [7.5 months]

Secondary Outcome Measures

  1. To assess toxicity [7.5 months]

  2. To determine survival [2 years]

  3. 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 [2 years]

  4. To compare plasma levels of VEGF-A, VEGF-C, VEGF-D, and CD133+ VEGFR2+ circulating endothelial progenitors [2 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:
19 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Locations

Site City State Country Postal Code
1 Memoral Sloan Kettering Basking Ridge (Follow Up Only) Basking Ridge New Jersey United States
2 Memorial Sloan Kettering Cancer Commack (Follow Up Only) Commack New York United States 11725
3 Memoral Sloan Kettering Westchester (Follow Up Only) Harrison New York United States 10604
4 Memorial Sloan Kettering Cancer Center New York New York United States 10065
5 Memorial Sloan Kettering Nassau (Follow Up Only) Uniondale New York United States 11553

Sponsors and Collaborators

  • Memorial Sloan Kettering Cancer Center

Investigators

  • Principal Investigator: Nancy Kemeny, M.D, Memorial Sloan Kettering Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

None provided.
Responsible Party:
Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT00200200
Other Study ID Numbers:
  • 04-086
  • NCT00263848
First Posted:
Sep 20, 2005
Last Update Posted:
Apr 27, 2022
Last Verified:
Apr 1, 2022

Study Results

No Results Posted as of Apr 27, 2022