A Randomized Phase II Study of Hepatic Arterial Infusion With Intravenous Irinotecan, 5FU and Leucovorin With or Without Panitumumab, in Patients With Wild Type KRAS Who Have Resected Hepatic Metastases From Colorectal Cancer
- 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.
- Completely resected hepatic metastases without current evidence of other metastatic
- Lab values within 14 days prior to registration:
- WBC > or = to 3.0 K/uL
- ANC > 1.5 K/uL
- Platelets > or = to 100,000/uL
- Creatinine <1.5 mg/dL
- HGB > or = to 9 gm/dL Renal function (≤ 10 days prior to enrollment/randomization).
- Creatinine ≤1.5 mg/dL or creatinine clearance ≥ 50 mL/min calculated by the
Cockcroft-Gault method as follows:
- Male creatinine clearance = (140 -age in years) x (weight in Kg) / (serum Cr in mg/dl
- Female creatinine clearance = (140 - age in years) x (weight in Kg) x 0.85 / (serum
Cr in mg/dl x 72) (use of creatinine clearance per protocol based on chemotherapy
regimen) Hepatic function, as follows: (≤ 10 days prior to enrollment/randomization)
- Aspartate aminotransferase (AST) (≤ 5 x ULN)
- Alanine aminotransferase (ALT) (≤ 5 x ULN)
- Total Bilirubin ≤ 1.5 mg/dl
- Magnesium ≥ lower limit of normal (≤ 48 hours prior to enrollment/ randomization.)
- Calcium ≥ lower limit of normal (≤ 48 hours prior to enrollment/ randomization.)
- 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.]
- Any investigational agent is acceptable if administered ≤ 30 days before
- KPS ≥ 60% (ECOG (or Karnofsky) performance status (preferably 0 or 1/≥ 60% for
- Histologically confirmed KRAS wild type(G12 mutations are not eligible. All other
mutations are eligible).
- Paraffin-embedded tumor tissue obtained from the primary tumor or metastasis
- Patients < 18 years of age.
- 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.
- Patients who have had prior anti-EGFr antibody therapy inhibitors and who have not
responded to this treatment will be excluded. However, patients who have responded to
prior anti-EGFR therapy are eligible.)
- Female patients who are pregnant or lactating - or planning to become pregnant within
6 months after the end of the treatment (female patients of child-bearing potential
must have negative pregnancy test ≤ 72 hours before enrollment).
- If a patient has any serious medical problems which may preclude receiving this type
- Patients with current evidence of hepatitis A, B, C (ie, active hepatitis)
- Patients with history or known presence 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 Panitumumab.
- Serious or non-healing active wound, ulcer, or bone fracture.
- History of interstitial lung disease e.g. pneumonitis or pulmonary fibrosis or
evidence of interstitial lung disease on baseline chest CT scan.
- Patients who have a diagnosis of Gilbert's disease.
- History of other malignancy, except:
- Malignancy treated with curative intent and with no known active disease present for
≥ 3 years prior to randomization and felt to be at low risk for recurrence by the
- Adequately treated non-melanomatous skin cancer or lentigo maligna without evidence
- Adequately treated cervical carcinoma in situ without evidence of disease