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

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ClinicalTrials.gov Identifier: NCT03069950
Recruitment Status : Withdrawn (Lack of accrual)
First Posted : March 3, 2017
Last Update Posted : May 21, 2019
Sponsor:
Collaborators:
The Cleveland Clinic
Oregon Health and Science University
Queens Cancer Center of Queens Hospital
Washington University School of Medicine
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

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.

Condition or disease Intervention/treatment Phase
Colorectal Adenocarcinoma Metastatic to the Liver Drug: Floxuridine (FUDR) Drug: Irinotecan (CPT-11) Drug: FLUOROURACIL Drug: PANITUMUMAB Drug: DEXAMETHASONE Drug: Leucovorin Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized, Multicenter Phase II Study of Panitumumab Plus FOLFIRI With or Without Hepatic Arterial Infusion as Second-Line Treatment in Patients With Wild Type RAS Who Have Unresectable Hepatic Metastases From Colorectal Cancer
Actual Study Start Date : February 28, 2017
Actual Primary Completion Date : May 16, 2019
Actual Study Completion Date : May 16, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Panitumumab

Arm Intervention/treatment
Experimental: 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.
Drug: Floxuridine (FUDR)
5-Fluouracil (5FU) (1000 mg/m2/day continuous infusion over two days)

Drug: Irinotecan (CPT-11)
Irinotecan (CPT) (150 mg/m2 IV over 30 min to an hour) on Day 1 and Day 15.

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

Drug: PANITUMUMAB
Panitumumab (6 mg/kg IV over 60 min)

Drug: DEXAMETHASONE
flat dose of 25 mg on Day 1

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

Experimental: 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.
Drug: Floxuridine (FUDR)
5-Fluouracil (5FU) (1000 mg/m2/day continuous infusion over two days)

Drug: Irinotecan (CPT-11)
Irinotecan (CPT) (150 mg/m2 IV over 30 min to an hour) on Day 1 and Day 15.

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

Drug: PANITUMUMAB
Panitumumab (6 mg/kg IV over 60 min)

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




Primary Outcome Measures :
  1. Resection rate assessed using RECIST (version 1.1) [ Time Frame: 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03069950


Locations
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United States, New Jersey
Memorial Sloan Kettering Basking Ridge
Basking Ridge, New Jersey, United States, 07920
Memorial Sloan Kettering Monmouth
Middletown, New Jersey, United States, 07748
United States, New York
Memorial Sloan Kettering Commack
Commack, New York, United States, 11725
Memoral Sloan Kettering Westchester
Harrison, New York, United States, 10604
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
The Cleveland Clinic
Oregon Health and Science University
Queens Cancer Center of Queens Hospital
Washington University School of Medicine
Investigators
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Principal Investigator: Andrea Cercek, MD Memorial Sloan Kettering Cancer Center

Additional Information:
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Responsible Party: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT03069950     History of Changes
Other Study ID Numbers: 16-1341
First Posted: March 3, 2017    Key Record Dates
Last Update Posted: May 21, 2019
Last Verified: May 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Memorial Sloan Kettering Cancer Center:
Hepatic Arterial Infusion
Floxuridine (FUDR)
Irinotecan (CPT-11)
FLUOROURACIL
PANITUMUMAB
16-1341
Additional relevant MeSH terms:
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Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Colonic Diseases
Rectal Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Adenocarcinoma
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Carcinoma
Dexamethasone
Irinotecan
Fluorouracil
Panitumumab
Floxuridine
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal