Trial document





This study has been imported from ClinicalTrials.gov without additional data checks.
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  DRKS00003685

Trial Description

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Title

Perioperative Chemotherapy With FOLFOX Plus Cetuximab Versus Adjuvant FOLFOX Plus Cetuximab for Patients With Resectable Liver Metastases of Colorectal Carcinoma

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Trial Acronym

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URL of the Trial

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Brief Summary in Lay Language

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?

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Brief Summary in Scientific Language

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.

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Do you plan to share individual participant data with other researchers?

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Description IPD sharing plan:

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Organizational Data

  •   DRKS00003685
  •   2012/05/08
  •   2010/12/20
  •   yes
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Secondary IDs

  •   NCT01266187  (ClinicalTrials.gov)
  •   CTC-A10-005  (RWTH Aachen University)
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Health Condition or Problem studied

  •   Liver Metastasis
  •   C78.7 -  Secondary malignant neoplasm of liver
  •   C18 -  Malignant neoplasm of colon
  •   C20 -  Malignant neoplasm of rectum
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Interventions/Observational Groups

  •   Procedure: adjuvant surgery + FOLFOX + cetuximab
  •   Procedure: perioperative/Folfox + cetuximab
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Characteristics

  •   Interventional
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  •   Randomized controlled trial
  •   Open (masking not used)
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  •   Active control (effective treament of control group)
  •   Treatment
  •   Parallel
  •   N/A
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Primary Outcome

- 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
- 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.

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Secondary Outcome

- 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

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  •  
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Recruitment

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  •   2011/07/31
  •   430
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
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Additional 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.

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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

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Addresses

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    • RWTH Aachen University
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    • RWTH Aachen University Hospital
    • Ulf P Neumann, Prof. 
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    • Ulf P Neumann, Prof. 
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Sources of Monetary or Material Support

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    • Bitte wenden Sie sich an den Sponsor / Please refer to primary sponsor
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Status

  •   Recruiting ongoing
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Trial Publications, Results and other Documents

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The parameters in ClinicalTrials.gov and DRKS are not identical. Therefore the data import from ClinicalTrials.gov required adjustments. For full details please see the DRKS FAQs .
  •   116
  •   2013/10/30
* This entry means the parameter is not applicable or has not been set.