Colorectal Adenocarcinoma Metastatic to the Liver
Conditions
Keywords
Hepatic Arterial Infusion, Floxuridine (FUDR), Irinotecan (CPT-11), FLUOROURACIL, PANITUMUMAB, 16-1341
Brief summary
The purpose of this study is to see if patients treated with both regional chemotherapy using the HAI pump and intravenous chemotherapy are able to have their liver tumors removed surgically (resected), versus treatment with only intravenous chemotherapy.
Interventions
5-Fluouracil (5FU) (1000 mg/m2/day continuous infusion over two days)
Irinotecan (CPT) (150 mg/m2 IV over 30 min to an hour) on Day 1 and Day 15.
DRUGFLUOROURACIL
5-Fluouracil (5FU) (1200 mg/m2/day continuous infusion over two days)
DRUGPANITUMUMAB
Panitumumab (6 mg/kg IV over 60 min)
DRUGDEXAMETHASONE
flat dose of 25 mg on Day 1
DRUGLeucovorin
Leucovorin (LV) (400 mg/m2 IV over 30 min to an hour)
Sponsors
The Cleveland Clinic
Oregon Health and Science University
Queens Cancer Center of Queens Hospital
Washington University School of Medicine
Memorial Sloan Kettering Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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 by the enrolling institution. * Patients must have a primary L sided colorectal cancer, (at or distal to the splenic flexure) * Confirmed RAS/RAF wild type tumor. Paraffin-embedded tumor tissue obtained from the primary tumor or metastasis * Have received prior treatment for metastatic disease with oxaliplatin-based regimen and either * Had disease progression OR * Had stable disease OR * Discontinued oxaliplatin due to neuropathy * Patients must meet the following criteria for unresectability as determined by two hepatobiliary surgeons and one radiologist: * When a margin negative resection would require resection of all three hepatic veins, both portal veins, or the retrohepatic vena cava. * Requiring a resection that leaves less than 2 hepatic segments (not including the caudate lobe) behind with adequate arterial/portal inflow, venous outflow and biliary drainage. \*\* \*\*A patient is considered resectable if the procedure includes a minor wedge or thermo-ablation encompassing 10% or less of the volume of the remaining 2 segments. * Patients liver metastases must comprise \<70% of the liver parenchyma. All patients must be clinically fit to undergo surgery as determined by the pre-operative evaluation * Lab values within 14 days prior to enrollment/randomization: * WBC ≥ 3.0 K/uL * ANC \> 1.5 K/uL * Platelets ≥ 100,000/uL * 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: 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: (≤ 10 days prior to enrollment/randomization) * Total Bilirubin ≤ 1.5 mg/dl * Calcium ≥ lower limit of normal (≤ 48 hours prior to enrollment/randomization) * KPS ≥ 60% (ECOG (or Karnofsky) performance status (preferably 0 or 1/≥ 60% for Karnofsky))
Exclusion criteria
* Patients \< 18 years of age * Patients who have received more than one chemotherapy regimen for metastatic disease * Patients who are chemotherapy naïve * Prior radiation to the liver (Prior radiation therapy to the pelvis is acceptable if completed at least 4 weeks prior to registration) * Active infection °Active infection includes patients with positive blood cultures * Prior treatment with HAI FUDR * Prior TACE * 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 and randomization, and must have a negative pregnancy test ≤ 72 hours prior to treatment start) * If a patient has any serious medical problems which may preclude receiving this type of treatment * 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. * 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 Gilberts disease * History of other malignancy, except: 1. 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 treating physician 2. Adequately treated non-melanomatous skin cancer or lentigo maligna without evidence of disease 3. Adequately treated cervical carcinoma in situ without evidence of disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Resection rate assessed using RECIST (version 1.1) | 3 months | Treatment evaluation will be done using RECIST (version 1.1) The patient will be assessed with repeat CT scans as specified. If at any time after 3 cycles (or 3 months) the patient is able to undergo a complete resection of all hepatic metastases they will proceed to operative assessment. |
Countries
United States
Outcome results
None listed