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Treatment Regimens for Patients With Resectable Liver Metastases (PANTER Study)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01266187
Recruitment Status : Terminated (Recruitment difficulities)
First Posted : December 24, 2010
Last Update Posted : September 22, 2015
Information provided by (Responsible Party):

Study Description
Brief Summary:
Is a perioperative chemotherapy based on FOLFOX and Cetuximab (K-RAS wild-type) associated with a higher rate of postoperative complications in patients with resectable colorectal liver metastases as compared to only adjuvant FOLFOX and chemotherapy? Are there any differences for disease free survival between periand postoperative treatment in patients with >3 liver metastases or at least one metastasis > or = 5 cm in diameter?

Condition or disease Intervention/treatment
Liver Metastasis Procedure: adjuvant surgery + FOLFOX + cetuximab Procedure: perioperative/Folfox + cetuximab

Detailed Description:
In recent years chemotherapy based on FOLFOX and cetuximab has become a standard treatment in patients with colorectal liver metastases. Recently, the analysis of the CELIM trial reported response rates of 70% in patients with initially unresectable colorectal liver metastases treated with FOLFOX + Cetuximab. 46% of the patients had their metastases R0 or R1 resected or a ablation by radiofrequency with an overall 34% R0 resection rate. In recent studies, adjuvant chemotherapy with FOLFOX leads to a prolongation of disease free survival after successful resection of colorectal liver metastases, but there is not sufficient data concerning a perioperative regimen. In only one study of Nordlinger et al. a trend in progression-free survival could be reached in patients receiving a perioperative FOLFOX-therapy, but without reaching statistical significance. Furthermore those patients displayed a significantly higher rate of postoperative complications and morbidity. Although the advantages of perioperative treatment are not proven, this concept has become more and more popular in recent years, mainly because of a lack of guidelines. Thus the aim of our study is to compare the complication rate of both therapeutical concepts. Furthermore, secondary objectives (disease-free survival, overall survival, resection rates, response rates, toxicities and quality of life) will be used to estimate the efficacy, feasibility, and safety of both regimens. Perioperative treatment probably has a better efficacy in patients with high tumor burden (>3 liver metastases or one metastasis > or = 5 cm in diameter) with effect on disease free survival and will be investigated in a subgroup analysis.

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 16 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Perioperative Chemotherapy With FOLFOX Plus Cetuximab Versus Adjuvant FOLFOX Plus Cetuximab for Patients With Resectable Liver Metastases of Colorectal Carcinoma
Study Start Date : July 2011
Primary Completion Date : September 2015
Study Completion Date : September 2015

Resource links provided by the National Library of Medicine

Drug Information available for: Cetuximab
U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: Arm B

12 weeks FOLFOX + cetuximab -> 4 weeks rest -> surgery

-> 4-8 weeks rest -> 12 weeks FOLFOX + cetuximab

Procedure: perioperative/Folfox + cetuximab

12 weeks FOLFOX + cetuximab -> 4 weeks rest -> surgery

-> 4-8 weeks rest -> 12 weeks FOLFOX + cetuximab

Active Comparator: Arm A
surgery -> 4-8 weeks rest -> 24 weeks FOLFOX + cetuximab
Procedure: adjuvant surgery + FOLFOX + cetuximab
surgery -> 4-8 weeks rest -> 24 weeks FOLFOX + cetuximab

Outcome Measures

Primary Outcome Measures :
  1. Clavien score (> grade 1) [ Time Frame: 1 year ]
    The first primary objective of the study is to compare the postoperative complication rate according to Clavien score (> grade 1) of a perioperative chemotherapy with a postoperative regimen

  2. Disease free survival [ Time Frame: 1 year ]
    A second primary objective of the study is to compare for the patient subgroup with >3 liver metastases or at least one metastasis > or = 5 cm in diameter the median disease free survival.

Secondary Outcome Measures :
  1. Secondary objectives [ Time Frame: 5 years ]

    Secondary Objectives:

    • To compare the overall disease-free survival.
    • To compare the overall survival.
    • To compare operation, resection and R0 rates.
    • To compare the safety and chemotherapy-associated toxicity (NCI-CTC V4.0)
    • To compare the effect of a perioperative therapy on healthrelated quality of life (EORTC QLQ-C30 + QLQ-LMC21).
    • To compare the number of cycles, dose intensity and dose modifications applied.
    • To evaluate the response rate (RECIST V1.1 no confirmation of response needed) after preoperative chemotherapy.
    • Resected liver mass

Eligibility Criteria

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Signed written informed consent obtained prior to any study-specific procedure.
  • Age > 18 years
  • Proven K-RAS wildtype in primary tumour or metastasis tissue
  • Diagnosis of resectable metachronous metastases after complete resection (R0) of primary tumour without gross or microscopic evidence of residual disease. or Diagnosis of resectable synchronous metastases after complete resection (R0) of primary tumour more than 1 month before study or Diagnosis of resectable synchronous metastases with sufficient evidence (i.e., CT scan or diagnostic laparoscopy) that both the primary tumour and liver metastases can be completely resected during the same procedure and resection of primary can be delayed 3-4 months.
  • Negative pregnancy test
  • Highly effective contraception during treatment and for at least 3 months thereafter in women (defined as pearl index < 1) and men, if the risk of conception exists
  • Planned start of study medication between 0 and 3 weeks post randomization
  • ECOG performance status 0 or 1 (Appendix 1)
  • Adequate hematology: neutrophils > 1,5 /nl, platelets > 100/nl, INR < 1,5, aPTT < 1,5 x UNL
  • Adequate biochemistry: total bilirubin < 1,5 x UNL, ASAT and ALAT < 5 x UNL, alkaline phosphatase < 5 x UNL, serum creatinine < 1,5, x UNL.

Exclusion Criteria:

  • Patients with any relationship of dependence to the sponsor or the investigator
  • Patients committed to an institution (court-ordered or by official orders)
  • Extrahepatic metastatic disease
  • Proven K-RAS mutation or unknown K-RAS mutational status in tumour tissue
  • Oxaliplatin-based adjuvant chemotherapy within 1 year before randomization
  • Neuropathy > or = grade 3 (NCI-CTC V4.0) during prior oxaliplatin-based chemotherapy
  • Any prior chemotherapy for metastatic disease
  • Previous treatment with EGFR antibodies
  • Prior non-colorectal malignancies, except adequately treated basalioma of the skin or carcinoma in situ of the cervix.
  • Bleeding diathesis or coagulation disorders
  • Females with a positive pregnancy test (within 14 days before treatment start) or breast feeding
  • Fertile women (<2 years after last menstruation) and women of childbearing potential not willing to use effective means of contraception
  • History of psychiatric disability judged by the investigator to be clinically significant, precluding informed consent or interfering with compliance for drug intake
  • Clinically significant (i.e. active) cardiovascular disease, e.g. cerebrovascular accidents (<6 months prior to randomization), myocardial infarction (<1 year prior to randomization), Congestive heart failure (NYHA Grades III or IV), uncontrolled hypertension while receiving chronic medication, unstable angina pectoris, significant arrhythmia
  • Known peripheral neuropathy, including oxaliplatininduced

    > or = grade 1 (NCI-CTC V4.0). Absence of deep tendon reflexes being the sole neurologicl abnormality does not render the patient ineligible

  • Known DPD-deficiency (Dihydropyrimidinedehydrogenase)
  • Organ allografts requiring immunosuppressive therapy
  • Serious, non-healing wound, ulcer or bone fracture
  • Serious intercurrent infections (uncontrolled or requiring treatment)
  • Current or recent (within 28 days prior to randomisation) treatment with another investigational drug or participation in another investigational study
  • Any contraindications against study medication (including auxiliary substances)
  • Patients unwilling to consent the saving and propagation of pseudonymized medical data for study reasons
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01266187

Department of Surgery, University Hospital Aachen
Aachen, NRW, Germany, 52074
Sponsors and Collaborators
RWTH Aachen University
Study Director: Ulf P Neumann, Prof. RWTH Aachen University Hospital
More Information

Responsible Party: RWTH Aachen University
ClinicalTrials.gov Identifier: NCT01266187     History of Changes
Other Study ID Numbers: CTC-A10-005
First Posted: December 24, 2010    Key Record Dates
Last Update Posted: September 22, 2015
Last Verified: September 2015

Keywords provided by RWTH Aachen University:
liver metastasis

Additional relevant MeSH terms:
Neoplasm Metastasis
Neoplasms, Second Primary
Liver Neoplasms
Neoplastic Processes
Pathologic Processes
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Antineoplastic Agents
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Protective Agents
Vitamin B Complex
Growth Substances