Clinical trial NCT01312857: Study of Hepatic Arterial Infusion With Intravenous Irinotecan, 5FU and Leucovorin With or Without Panitumumab, in Patients With Wild Type RAS Who Have Resected Hepatic Metastases From Colorectal Cancer
Official title: A Randomized Phase II Study of Hepatic Arterial Infusion With Intravenous Irinotecan, 5FU and Leucovorin With or Without Panitumumab, in Patients With Wild Type RAS Who Have Resected Hepatic Metastases From Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Colorectal Cancer
Keywords: colon
rectal
liver
AMG 954 (Panitumumab)
DEXAMETHASONE
FLOXURIDINE
FLUOROURACIL
IRINOTECAN (CPT-11) CAMPTOSAR
LEUCOVORIN
10-137
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
Collaborators: name: Amgen
First posted: 2011-03-11
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to see if Panitumumab plus the other treatments will increase the time of remission. Remission means that there is no sign of the cancer.


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.
* Completely resected hepatic metastases without current evidence of other metastatic disease.
* Lab values ≤ 14 days prior to treatment start:
* WBC ≥ 3.0 K/uL
* ANC \> 1.5 K/uL
* Platelets ≥ 100,000/uL
* Creatinine \<1.5 mg/dL
* HGB ≥ 9 gm/dL Renal function (≤ 14 days prior to treatment start).
* 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 x 72)
* 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: (≤ 14 days prior to treatment start)
* 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 treatment start.)
* Calcium ≥ lower limit of normal (≤ 48 hours prior to treatment start.)
* 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 registration
* KPS ≥ 60% (ECOG (or Karnofsky) performance status (preferably 0 or 1/≥ 60% for Karnofsky)
* Histologically confirmed all RAS wild type.
* Paraffin-embedded tumor tissue obtained from the primary tumor or metastasis (Prior to

Exclusion Criteria:

* 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 registration).
* If a patient has any serious medical problems which may preclude receiving this type of treatment.
* 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 registration and felt to be at low risk for recurrence by the treating physician
* Adequately treated non-melanomatous skin cancer or lentigo maligna without evidence of disease
* Adequately treated cervical carcinoma in situ without evidence of disease

Primary outcomes:
measure: to determine if panitumumab with Hepatic Arterial Infusion (HAI) in combination with systemic chemotherapy can increase the recurrence free survival (RFS) for colorectal cancer patients with resected liver metastases
timeFrame: 2 years
Secondary outcomes:
measure: to assess toxicity as per the NCI Common Toxicity Criteria
timeFrame: Day 1 of each cycle
measure: to determine survival
timeFrame: 2 years
measure: to analyze tumor tissue for predictive biomarkers
timeFrame: 2 years
Other outcomes:
Locations:
city: Basking Ridge
country: United States
facility: Memorial Sloan Kettering Basking Ridge
state: New Jersey
city: Middletown
country: United States
facility: Memorial Sloan Kettering Monmouth
state: New Jersey
city: Montvale
country: United States
facility: Memorial Sloan Kettering Bergen
state: New Jersey
city: Commack
country: United States
facility: Memorial Sloan Kettering Commack
state: New York
city: Harrison
country: United States
facility: Memorial Sloan Kettering Westchester
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Rockville Centre
country: United States
facility: Memorial Sloan Kettering Rockville Centre
state: New York
city: Uniondale
country: United States
facility: Memorial Sloan Kettering Nassau
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Nancy Kemeny, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kemeny NE, Chou JF, Capanu M, Chatila WK, Shi H, Sanchez-Vega F, Kingham TP, Connell LC, Jarnagin WR, D'Angelica MI. A Randomized Phase II Trial of Adjuvant Hepatic Arterial Infusion and Systemic Therapy With or Without Panitumumab After Hepatic Resection of KRAS Wild-type Colorectal Cancer. Ann Surg. 2021 Aug 1;274(2):248-254. doi: 10.1097/SLA.0000000000004923.