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

NCT01384994 | Unknown Phase 2

• 1 other identifier: PARLIM
• Study Type: interventional
• Target: 111
• Locations: 1 country
• Sites: 1

Brief 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

Keywords

Colorectal Cancer; PARLIM; KRAS Wildtype; Liver metastases

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival

  2 years after randomisation

Secondary Outcomes (2)

• Tolerability and side effects

  approximate 6 months after randomisation

• Overall Survival

  2 years after randomisation

Study Arms (2)

FOLFOX + Panitumumab

EXPERIMENTAL

Drug: Folic Acid; Drug: 5-FU; Drug: Oxaliplatin; Drug: Panitumumab

FOLFOX

ACTIVE COMPARATOR

Drug: Folic Acid; Drug: 5-FU; Drug: Oxaliplatin

Interventions

Folic Acid DRUG

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

FOLFOX + Panitumumab

5-FU DRUG

400 mg/m2 bolus iv, d1, q2w

FOLFOX + Panitumumab

Oxaliplatin DRUG

85 mg/m2 d1, q2w

FOLFOX + Panitumumab

Panitumumab DRUG

6 mg/kg BW every 2 weeks

FOLFOX + Panitumumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient has provided written informed consent.
• R0-resection of liver metastasis, at least four weeks but not longer than 8 weeks ago.
• Histologically confirmed diagnosis of metastatic colorectal cancer confined to the liver
• KRAS-wildtype of the tumor
• Age 18 years or older
• ECOG performance status 0-1
• Females with child-bearing potential must use adequate contraceptive measures
• Relevant toxicities of previous treatments must have subsided
• Magnesium \>= lower limit of normal; Calcium \>= lower limit of normal
• Normal cardiac function demonstrated by ECG and echocardiogram (LVEF ≥ 55%)
• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia
• Adequate organ function as defined by Table 1:
• Hematologic: ANC (absolute neutrophil count) \>= 1.5 G/L, Leucocytes \> 3.0 G/L, Hemoglobin \>= 9 g/dL, Platelets \>= 100 G/L

You may not qualify if:

• Known manifestations of metastatic disease
• Progression during preoperative treatment
• Missing KRAS mutation status of the tumor
• Contraindication against therapy with 5-fluorouracil/ folinic acid or oxaliplatin
• Known intolerability of panitumumab
• Known DPD deficiency
• Polyneuropathy \> grade 1 (NCI-CTCv4) which precludes the use of oxaliplatin
• Evidence of ascites or cirrhosis
• Patient is pregnant or lactating or planning to become pregnant within 6 months after end of treatment
• Subject (male or female) is not willing to use highly effective methods of contraception (per institutional standard) during treatment and for 6 months (male or female) after the end of treatment
• Has had a major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrolment, or there is an anticipated need for major surgical procedure during the course of the study
• Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) \<= 1 year before enrolment/randomization
• History of interstitial lung disease e.g. pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease on baseline chest CT scan
• Has a concurrent disease or condition that would make the subject inappropriate for study participation or would interfere with the subject's safety.
• Has any psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.

Sponsors & Collaborators

• PD Dr. med. Volker Heinemann: lead
• Amgen: collaborator

Study Sites (1)

Ludwig-Maximilians - University of Munich

Munich, 81377, Germany

RECRUITING

Related Publications (1)

• Modest DP, Karthaus M, Kasper S, Moosmann N, Keitel V, Kiani A, Uhlig J, Jacobasch L, Fischer V Weikersthal L, Fuchs M, Kaiser F, Lerchenmuller C, Sent D, Junghanss C, Held S, Lorenzen S, Kaczirek K, Jung A, Stintzing S, Heinemann V. FOLFOX plus panitumumab or FOLFOX alone as additive therapy following R0/1 resection of RAS wild-type colorectal cancer liver metastases - The PARLIM trial (AIO KRK 0314). Eur J Cancer. 2022 Sep;173:297-306. doi: 10.1016/j.ejca.2022.07.012. Epub 2022 Aug 12.

  PMID: 35970102 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Folic Acid; Fluorouracil; Oxaliplatin; Panitumumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Coordination Complexes; Organic Chemicals; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Volker Heinemann, Prof. Dr. med.

CONTACT

+49 89 7095; volker.heinemann@med.uni-muenchen.de

Clemens Gießen, Dr. med.

CONTACT

+49 89 7095; clemens.giessen@med.uni-muenchen.de

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor Delegatated Person

Study Record Dates

• First Submitted: May 2, 2011
• First Posted: June 29, 2011
• Study Start: August 1, 2011
• Primary Completion: August 1, 2013
• Study Completion: August 1, 2014
• Last Updated: July 9, 2012

Record last verified: 2012-07

Locations

DE (1)