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A Phase II Study of Perioperative Chemotherapy Plus Panitumumab in Patients With Colorectal Cancer Liver Metastases

Phase 2
18 Years
Open (Enrolling)
Colorectal Cancer, Liver Metastases

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Trial Information

A Phase II Study of Perioperative Chemotherapy Plus Panitumumab in Patients With Colorectal Cancer Liver Metastases

Emerging data suggests that KRAS mutation is a strong predictor for resistance to EGFR
antagonist therapy. In the KRAS wild-type cohort, the addition of EGFR antagonists to
chemotherapy has been shown to improve RR and PFS. Improved response rate to neoadjuvant
chemotherapy would be expected to improve surgical outcomes for patients with CRCLM. We
therefore wish to test the hypothesis that the combination of FOLFOX/FOLFIRI and
panitumumab, given perioperatively to patients with wild-type KRAS CRCLM will improve
outcome, compared to historical control, in optimally resectable patients. As this patient
population remains at high risk for recurrence post-chemotherapy, we also wish to explore
the tolerability and efficacy of continued panitumumab monotherapy for an additional 6

As opposed to most clinical trials for advanced colorectal cancer where the majority are
treated with palliative intent, patients in this trial will all be treated aggressively with
curative intent at the outset. There is also the additional benefit of assessment of tumor
tissue after treatment with a biologic agent.

Inclusion Criteria:

- Patients must have histologically or cytologically confirmed colorectal cancer with
available tissue to test for K-RAS mutation. Biopsy is required if no archived tissue
is available. K-RAS mutation status must be confirmed prior to registration. Only
patients with K-RAS wild-type cancers are eligible.

- Patients must have measurable disease, defined as at least one lesion that can be
accurately measured in at least one dimension (longest diameter to be recorded) as
>20 mm with conventional techniques or as >10 mm with spiral CT scan.

- Patients must have resectable hepatic colorectal metastases.

- Patients may have synchronous unresected primary disease upon registration. Primary
must be resectable, either at same laparotomy or at separate laparotomy from liver

- Age >18 years.

- Patients must have Eastern Cooperative Oncology Group Performance Status (ECOG PS) of
0 or 1.

- Patients must have normal organ and marrow function as defined below:

leukocytes > 3,000/mcL absolute neutrophil count >1,500/mcL platelets >100,000/mcL
hemoglobin > 90 g/L total bilirubin < 2 x upper limit of normal (< 1.5 x ULN for
FOLFIRI), AST(SGOT) and ALT(SGPT)< 5 x upper limit of normal (< 3 x ULN for
FOLFIRI);creatinine within normal institutional limits OR- creatinine clearance >50
mL/min/1.73 m2 for patients with creatinine levels above institutional normal

- Appropriate imaging investigations, including CT or MRI of chest/abdomen/pelvis.
Other scans if clinically indicated may be performed. All imaging studies must be
performed within 28 days of study entry.

- Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry, for
the duration of study and for a period of six months after cessation of study
therapy. Should a woman become pregnant or suspect she is pregnant while
participating in this study, she must inform her treating physician immediately.

- Ability to understand and the willingness to sign a written informed consent

Exclusion Criteria

- Patients must have had no previous systemic treatment in the adjuvant or metastatic
setting within 6 months of registration.

- Patients may not have had prior treatment with an EGFR antagonist.

- Patients may not have a history of other malignancies, except: adequately treated
non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other
solid malignancies curatively treated with no evidence of disease for ≥ 5 years.

- Patients may not have extrahepatic metastatic disease. Patients who have had prior
surgical resection for hepatic metastases or extrahepatic disease (eg. pulmonary
metastases) are also excluded from this study.

- Patients may not have pre-existing chronic hepatic disease (eg. cirrhosis, chronic
active hepatitis B or C)

- History of allergic reactions, or intolerance, attributed to compounds of similar
chemical or biologic composition to 5-fluorouracil, oxaliplatin, or panitumumab.

- Patients being considered for irinotecan must not have a history of Gilbert's

- Patients may not have uncontrolled inter-current illness including, but not limited
to, ongoing or active infection, or psychiatric illness/social situations that would
limit compliance with study requirements.

- HIV-positive patients on combination antiretroviral therapy are ineligible because of
the potential for pharmacokinetic interactions with the agents used in this study.
In addition, these patients are at increased risk of lethal infections when treated
with marrow-suppressive therapy.

- Patients with active cardiovascular disease, i.e., unstable angina, New York Heart
Association grade II or greater congestive heart failure, serious cardiac arrhythmia
requiring medications, or grade II or greater peripheral vascular disease. In
addition, patients with arterial or venous thrombosis, myocardial infarction, and
cerebral vascular accidents (stroke / transient ischemic attach (TIA)) within 6
months prior to study entry will be excluded.

- Patients with a history of interstitial pneumonitis or pulmonary fibrosis will be

- Organ allografts requiring immunosuppressive therapy.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To determine the 2 year disease-free survival rate in patients with resectable colorectal liver metastases treated with FOLFOX/FOLFIRI + panitumumab for 2 months pre-operatively and 4 months post-operatively, followed by panitumumab alone for 6 months.

Outcome Time Frame:

2-years post-therapy

Safety Issue:


Principal Investigator

Stephen Welch, MD

Investigator Role:

Study Chair

Investigator Affiliation:

London Regional Cancer Center


Canada: Health Canada

Study ID:




Start Date:

August 2010

Completion Date:

December 2014

Related Keywords:

  • Colorectal Cancer
  • Liver Metastases
  • colorectal cancer
  • liver metastases
  • panitumumab
  • Colorectal cancer with liver metastases
  • Colorectal Neoplasms
  • Neoplasm Metastasis
  • Neoplasms, Second Primary
  • Liver Neoplasms