Panitumumab After Resection of Liver Metastases From Colorectal Cancer in KRAS Wild-type Patients

Summary

Up to 50% of patients with colorectal cancer (CRC) develop liver metastasis during the course of their disease. In 30-40% of patients metastasis is confined to the liver. In these patients R0-resection of metastases may contribute to marked improvement of overall survival. Primary resection of liver metastasis is possible in about 15-20% of patients (Scheele 2005, Petrelli 2005). Recent studies indicate that perioperative chemotherapy may improve survival after resection of liver metastases (Portier 2007, Nordlinger 2007). Nevertheless, there is evidence that 70-80% of patients have recurrent disease after resection of liver metastasis. Stratification for the risk of recurrence may be performed using the FONG-score (Fong 1999).

This study is designed to investigate the efficacy of postoperative chemotherapy combined with an anti-EGFR treatment using panitumumab.

The majority of patients present to the surgeon after chemotherapeutic pretreatment with various not necessarily standardized regimens. Also postoperative therapy after resection of liver metastasis is not a clearly defined standard of care in Germany.

Based on the study by Nordlinger et al. an oxaliplatin-based regimen is chosen for postoperative therapy (Nordlinger 2008). For reasons of practicability mFOLFOX6 was selected as the chemotherapy backbone for additive treatment (Allegra 2010).

Also, there is evidence that the combination of FOLFOX with panitumumab is associated with enhanced antitumor activity (Douillard et al. ESMO 2009). The experimental treatment arm will therefore evaluate the combination of FOLFOX plus panitumumab. Since in colorectal cancer monoclonal antibodies directed against the EGFR are not active in KRAS mutant patients, the experimental arm including panitumumab will only be performed in KRAS wild-type patients (Amado 2008).

The planned study aims to assess the efficacy of postoperative therapy with FOLFOX plus panitumumab followed by maintenance with panitumumab for 3 months in KRAS wild-type patients, compared to the historical data for standard FOLFOX chemotherapy alone, which are verified by a randomised control group without the antibody. (Figure 1: Study Design).

The study will allow preoperative treatment with regimens such as FOLFIRI, XELIRI, FOLFOX or XELOX +/-bevacizumab or +/- cetuximab. However, only those patients will be considered eligible who did not progress during preoperative therapy.

After surgery, a treatment-free interval of at least 4 weeks, but no longer than 8 weeks will be granted.

KRAS-wild-type patients (60% of all pts) will then be randomized in a 2:1 ratio to an experimental arm with FOLFOX + panitumumab or to a reference arm with FOLFOX alone. Combination treatment will be performed for a duration of 3 months, after which patients in the experimental arm will receive maintenance therapy with panitumumab for further 3 months. In the reference arm, treatment will, however, be ended after 3 months.

Conditions

• Colorectal Cancer
• KRAS Wildtype
• After Resection of Liver Metastases

Interventions

DRUG

Folic Acid

400 mg/m2, 2h infusion, d1, q2w

DRUG

5-FU

400 mg/m2 bolus iv, d1, q2w

DRUG

5-FU

2400 mg/m2 46-h infusion, d1-2, q2w

DRUG

Oxaliplatin

85 mg/m2 d1, q2w

DRUG

Panitumumab

6 mg/kg BW every 2 weeks

DRUG

Panitumumab

Panitumumab maintenance phase (3 months) 9mg/kg BW every 3 weeks

DRUG

Folic Acid

400 mg/m2, 2-h infusion, d1, q2w

DRUG

5-FU

400 mg/m2 bolus iv, d1, q2w

DRUG

5-FU

2400 mg/m2 46-h infusion, d1-2, q2w

DRUG

Oxaliplatin

85 mg/m2 d1, q2w

Sponsors & Collaborators

• Amgen

  collaborator INDUSTRY

• PD Dr. med. Volker Heinemann

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2011-08-31

Primary Completion

2013-08-31

Completion

2014-08-31

Countries

• Germany

Study Locations