Study of Chemotherapy With or Without Hepatic Arterial Infusion for Patients With Unresectable Metastatic Colorectal Cancer to the Liver

Memorial Sloan Kettering Cancer Center (MSK)

Status and phase: Withdrawn; Phase 2

Conditions: Colorectal Adenocarcinoma Metastatic to the Liver

Treatments: Drug: DEXAMETHASONE; Drug: PANITUMUMAB; Drug: FLUOROURACIL; Drug: Leucovorin; Drug: Irinotecan (CPT-11); Drug: Floxuridine (FUDR)

Study type: Interventional

Funder types: Other

Identifiers

NCT03069950

16-1341

Details and patient eligibility

About

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.

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

  • Patient"s 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 Gilbert"s 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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0 participants in 2 patient groups

HAI FUDR/Dex in addition to Pmab plus FOLFIRI

Experimental group

Description:

Panitumumab plus FOLFIRI on Day 1 and Day 15 of each cycle. HAI pump therapy with FUDR and Dex on Day 1 of each cycle. Patients will start protocol therapy approximately 2 weeks after surgery. All patients will receive Panitumumab (6 mg/kg IV over 60 min). The HAI FUDR group will receive FOLFIRI in the following dosing; 5-Fluouracil (5FU) (1000 mg/m2/day continuous infusion over two days), Leucovorin (LV) (400 mg/m2 IV over 30 min to an hour), and Irinotecan (CPT) (150 mg/m2 IV over 30 min to an hour) on Day 1 and Day 15.

Treatment:

Drug: DEXAMETHASONE

Drug: PANITUMUMAB

Drug: FLUOROURACIL

Drug: Leucovorin

Drug: Irinotecan (CPT-11)

Drug: Floxuridine (FUDR)

Pmab plus FOLFIRI alone

Experimental group

Description:

The dosing of FOLFIRI in the systemic arm will be 5-Fluouracil (5FU) (1200 mg/m2/day continuous infusion over two days), Leucovorin (LV) (400 mg/m2 IV over 30 min to an hour), bolus 5FU 400mg/ m2 and Irinotecan (CPT) (150 mg/m2 IV over 30 min to an hour) on Day 1 and 15.

Treatment:

Drug: PANITUMUMAB

Drug: FLUOROURACIL

Drug: Leucovorin

Drug: Irinotecan (CPT-11)

Drug: Floxuridine (FUDR)