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

NCT ID: NCT03069950

Last Updated: 2019-05-21

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-02-28
• Study Completion Date: 2019-05-16

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.

Conditions

Colorectal Adenocarcinoma Metastatic to the Liver

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

HAI FUDR/Dex in addition to Pmab plus FOLFIRI

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.

Group Type: EXPERIMENTAL

Floxuridine (FUDR)

Intervention Type: DRUG

5-Fluouracil (5FU) (1000 mg/m2/day continuous infusion over two days)

Irinotecan (CPT-11)

Intervention Type: DRUG

Irinotecan (CPT) (150 mg/m2 IV over 30 min to an hour) on Day 1 and Day 15.

FLUOROURACIL

Intervention Type: DRUG

5-Fluouracil (5FU) (1200 mg/m2/day continuous infusion over two days)

PANITUMUMAB

Intervention Type: DRUG

Panitumumab (6 mg/kg IV over 60 min)

DEXAMETHASONE

Intervention Type: DRUG

flat dose of 25 mg on Day 1

Leucovorin

Intervention Type: DRUG

Leucovorin (LV) (400 mg/m2 IV over 30 min to an hour)

Pmab plus FOLFIRI alone

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.

Group Type: EXPERIMENTAL

Floxuridine (FUDR)

Intervention Type: DRUG

5-Fluouracil (5FU) (1000 mg/m2/day continuous infusion over two days)

Irinotecan (CPT-11)

Intervention Type: DRUG

Irinotecan (CPT) (150 mg/m2 IV over 30 min to an hour) on Day 1 and Day 15.

FLUOROURACIL

Intervention Type: DRUG

5-Fluouracil (5FU) (1200 mg/m2/day continuous infusion over two days)

PANITUMUMAB

Intervention Type: DRUG

Panitumumab (6 mg/kg IV over 60 min)

Leucovorin

Intervention Type: DRUG

Leucovorin (LV) (400 mg/m2 IV over 30 min to an hour)

Interventions

Floxuridine (FUDR)

5-Fluouracil (5FU) (1000 mg/m2/day continuous infusion over two days)

Intervention Type: DRUG

Irinotecan (CPT-11)

Irinotecan (CPT) (150 mg/m2 IV over 30 min to an hour) on Day 1 and Day 15.

Intervention Type: DRUG

FLUOROURACIL

5-Fluouracil (5FU) (1200 mg/m2/day continuous infusion over two days)

Intervention Type: DRUG

PANITUMUMAB

Panitumumab (6 mg/kg IV over 60 min)

Intervention Type: DRUG

DEXAMETHASONE

flat dose of 25 mg on Day 1

Intervention Type: DRUG

Leucovorin

Leucovorin (LV) (400 mg/m2 IV over 30 min to an hour)

Intervention Type: DRUG

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 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Cleveland Clinic

OTHER

Sponsor Role: collaborator

Oregon Health and Science University

OTHER

Sponsor Role: collaborator

Queens Cancer Center of Queens Hospital

OTHER

Sponsor Role: collaborator

Washington University School of Medicine

OTHER

Sponsor Role: collaborator

Memorial Sloan Kettering Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Andrea Cercek, MD

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Locations

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, United States

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, United States

Memorial Sloan Kettering Commack

Commack, New York, United States

Memoral Sloan Kettering Westchester

Harrison, New York, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Countries

United States

Related Links

http://www.mskcc.org/mskcc/html/44.cfm

Memorial Sloan Kettering Cancer Center

Other Identifiers

16-1341

Identifier Type: -

Identifier Source: org_study_id