Study of Hepatic Arterial Infusion With Intravenous Irinotecan, 5FU and Leucovorin With or Without Panitumumab, in Patients With Wild Type KRAS Who Have Resected Hepatic Metastases From Colorectal Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Memorial Sloan-Kettering Cancer Center
Sponsor:
Collaborator:
Amgen
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT01312857
First received: March 8, 2011
Last updated: April 24, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Metastatic Colorectal Cancer
Drug: panitumumab
Drug: Randomization to No Panitumumab
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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 KRAS Who Have Resected Hepatic Metastases From Colorectal Cancer

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • 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 [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • to assess toxicity as per the NCI Common Toxicity Criteria [ Time Frame: Day 1 of each cycle ] [ Designated as safety issue: Yes ]
    Toxicities will be recorded as adverse events on the Adverse Event case report form and must be graded using The National Cancer Institute's Common Toxicity Criteria (CTC)version 4.0 with the exception of skin- or nail-related toxicities, which must be graded using CTC version 3.0 with modifications

  • to determine survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • to analyze tumor tissue for predictive biomarkers [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    (such as NRAS, BRAF, PIK3CA, AKT1 and MEK1), and correlate with patient progression and survival following therapy.


Estimated Enrollment: 78
Study Start Date: March 2011
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Randomization to panitumumab
Patients whose liver metastases have been completely resected will be randomized Arm A will receive Panitumumab in addition to HAI FUDR/Dexamethasone plus systemic CPT-11/5FU/LV
Drug: panitumumab

All patients receive HAI FUDR (0.12 mg/kg/day X kg X pump volume) / pump flow rate and Dexamethasone flat dose of 25 mg on days 1.

All patients receive CPT-11 (150 mg/m2 IV over 30 min to an hour), Leucovorin (400 mg/m2 IV, over 30 min to an hour) and 5FU (1000 mg/m2/day continuous infusion over two days) on days 15 and 29 Randomization to panitumumab 6 mg/kg day 15 and 29 Each cycle repeats every 36 days for a total of 6 cycles

Experimental: Randomization to No Panitumumab
Patients whose liver metastases have been completely resected will be randomized and patients randomized to Arm B will receive HAI FUDR/Dex plus systemic CPT-11/5FU/LV alone.
Drug: Randomization to No Panitumumab

All patients receive HAI FUDR (0.12 mg/kg/day X kg X pump volume) / pump flow rate and Dexamethasone flat dose of 25 mg on days 1.

All patients receive CPT-11 (150 mg/m2 IV over 30 min to an hour), Leucovorin (400 mg/m2 IV, over 30 min to an hour) and 5FU (1000 mg/m2/day continuous infusion over two days) on days 15 and 29 Randomization (to no panitumumab) Each cycle repeats every 36 days for a total of 6 cycles


  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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 at MSKCC.
  • Completely resected hepatic metastases without current evidence of other metastatic disease.
  • Lab values within 14 days prior to registration:
  • WBC > or = to 3.0 K/uL
  • ANC > 1.5 K/uL
  • Platelets > or = to 100,000/uL
  • Creatinine <1.5 mg/dL
  • HGB > or = to 9 gm/dL 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:

  • 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)
  • 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 enrollment/ randomization.)
  • Calcium ≥ lower limit of normal (≤ 48 hours prior to enrollment/ randomization.)
  • 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 enrollment/randomization
  • KPS ≥ 60% (ECOG (or Karnofsky) performance status (preferably 0 or 1/≥ 60% for Karnofsky)
  • Histologically confirmed KRAS wild type(G12 mutations are not eligible. All other mutations are eligible).
  • Paraffin-embedded tumor tissue obtained from the primary tumor or metastasis

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 enrollment).
  • 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 randomization 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01312857

Contacts
Contact: Nancy Kemeny, MD 646-888-4180
Contact: Michael D'Angelica, MD 212-639-3226

Locations
United States, New Jersey
Memorial Sloan-Kettering Cancer Center at Basking Ridge Recruiting
Basking Ridge, New Jersey, United States, 07920
Contact: Nancy Kemeny, MD    646-888-4180      
United States, New York
Memorial Sloan-Kettering Cancer Center @ Suffolk Recruiting
Commack, New York, United States, 11725
Contact: Nancy Kemeny, MD    646-888-4180      
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Nancy Kemeny, MD    646-888-4180      
Contact: Michael D'Angelica, MD    212-639-3226      
Principal Investigator: Nancy Kemeny, MD         
Memorial Sloan-Kettering Cancer Center at Mercy Medical Center Recruiting
Rockville Centre, New York, United States, 11570
Contact: Nancy Kemeny, MD    646-888-4180      
Memorial Sloan-Kettering Cancer Center at Phelps Memorial Hospital Center Recruiting
Sleepy Hollow, New York, United States, 10591
Contact: Nancy Kemeny, MD    646-888-4180      
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Amgen
Investigators
Principal Investigator: Nancy Kemeny, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT01312857     History of Changes
Other Study ID Numbers: 10-137
Study First Received: March 8, 2011
Last Updated: April 24, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Memorial Sloan-Kettering Cancer Center:
colon
rectal
liver
AMG 954 (Panitumumab)
DEXAMETHASONE
FLOXURIDINE
FLUOROURACIL
IRINOTECAN (CPT-11) CAMPTOSAR
LEUCOVORIN
10-137

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Irinotecan
BB 1101
Antibodies, Monoclonal
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal

ClinicalTrials.gov processed this record on September 22, 2014