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

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT01312857

Collaborator

Amgen (Industry)

Enrollment

Locations

Arms

144

Anticipated Duration (Months)

9.4

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Metastatic Colorectal Cancer	Drug: panitumumab Drug: Randomization to No Panitumumab	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

75 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (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 RAS Who Have Resected Hepatic Metastases From Colorectal Cancer

Actual Study Start Date :

Mar 1, 2011

Anticipated Primary Completion Date :

Mar 1, 2023

Anticipated Study Completion Date :

Mar 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
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

Arm

Intervention/Treatment

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

Outcome Measures

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 [2 years]

Secondary Outcome Measures

to assess toxicity as per the NCI Common Toxicity Criteria [Day 1 of each cycle]
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 [2 years]
to analyze tumor tissue for predictive biomarkers [2 years]
(such as NRAS, BRAF, PIK3CA, AKT1 and MEK1), and correlate with patient progression and survival following therapy.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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 at MSKCC.
Completely resected hepatic metastases without current evidence of other metastatic disease.
Lab values ≤ 14 days prior to treatment start:
WBC ≥ 3.0 K/uL
ANC > 1.5 K/uL
Platelets ≥ 100,000/uL
Creatinine <1.5 mg/dL
HGB ≥ 9 gm/dL Renal function (≤ 14 days prior to treatment start).
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: (≤ 14 days prior to treatment start)
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 treatment start.)
Calcium ≥ lower limit of normal (≤ 48 hours prior to treatment start.)
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 registration
KPS ≥ 60% (ECOG (or Karnofsky) performance status (preferably 0 or 1/≥ 60% for Karnofsky)
Histologically confirmed all RAS wild type.
Paraffin-embedded tumor tissue obtained from the primary tumor or metastasis (Prior to

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 registration).
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 registration 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

Locations

	Site	City	State	Country	Postal Code
1	Memorial Sloan Kettering Basking Ridge	Basking Ridge	New Jersey	United States	07920
2	Memorial Sloan Kettering Monmouth	Middletown	New Jersey	United States	07748
3	Memorial Sloan Kettering Bergen	Montvale	New Jersey	United States	07645
4	Memorial Sloan Kettering Commack	Commack	New York	United States	11725
5	Memorial Sloan Kettering Westchester	Harrison	New York	United States	10604
6	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
7	Memorial Sloan Kettering Rockville Centre	Rockville Centre	New York	United States	11570
8	Memorial Sloan Kettering Nassau	Uniondale	New York	United States	11553