Liver MetastasisNCT01266187
Treatment Regimens for Patients With Resectable Liver Metastases (PANTER Study)
A study testing adjuvant surgery + FOLFOX + cetuximab and perioperative/Folfox + cetuximab in people with Liver Metastasis, run by RWTH Aachen University at 1 site in Germany.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Liver Metastasis
- What is being tested?
- adjuvant surgery + FOLFOX + cetuximab and perioperative/Folfox + cetuximab
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteGermany
- Study dates
- Jul 2011to Sep 2015
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
Germany1 site
Department of Surgery, University Hospital Aachen
Aachen, North Rhine-Westphalia, 52074
About this study
Official title: Perioperative Chemotherapy With FOLFOX Plus Cetuximab Versus Adjuvant FOLFOX Plus Cetuximab for Patients With Resectable Liver Metastases of Colorectal Carcinoma
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?
Read the 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.
- Conditions
- Liver Metastasis
- Being tested
- adjuvant surgery + FOLFOX + cetuximab, perioperative/Folfox + cetuximab
- Keywords
- FOLFOX, liver metastasis, cetuximab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
adjuvant surgery + FOLFOX + cetuximabProcedure or surgery
surgery -> 4-8 weeks rest -> 24 weeks FOLFOX + cetuximab
perioperative/Folfox + cetuximabProcedure or surgery
12 weeks FOLFOX + cetuximab -> 4 weeks rest -> surgery
-> 4-8 weeks rest -> 12 weeks FOLFOX + cetuximab
| Study group | Role | What they receive |
|---|---|---|
| Arm B | Experimental | 12 weeks FOLFOX + cetuximab -> 4 weeks rest -> surgery
-> 4-8 weeks rest -> 12 weeks FOLFOX + cetuximab Receives: Procedure: perioperative/Folfox + cetuximab |
| Arm A | Active comparator | surgery -> 4-8 weeks rest -> 24 weeks FOLFOX + cetuximab Receives: Procedure: adjuvant surgery + FOLFOX + cetuximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clavien score (> grade 1)
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
Measured: 1 year
Disease free survival
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.
Measured: 1 year
Secondary outcomes (1)
Secondary objectives
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
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Dec 2010 (estimated)
- Study startJul 2011
- Primary completionSep 2015
- Study completionSep 2015
Why it stopped: Recruitment difficulities
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Liver MetastasisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- RWTH Aachen University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ulf P Neumann, Prof., Study director, RWTH Aachen University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01266187
- Sponsor's protocol ID
- CTC-A10-005
- Status last verified
- Sep 2015
- First submitted
- 20 Dec 2010
- Last updated
- 22 Sep 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Sep 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Perioperative Chemotherapy With FOLFOX Plus Cetuximab Versus Adjuvant FOLFOX Plus Cetuximab for Patients With Resectable Liver Metastases of Colorectal Carcinoma
- ClinicalTrials.gov ID
- NCT01266187
- Acronym / sponsor ID
- CTC-A10-005
- Conditions
- Liver Metastasis
- Keywords
- FOLFOX, liver metastasis, cetuximab
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Recruitment difficulities
- Enrolment
- 16 participants (actual)
- Lead sponsor
- RWTH Aachen UniversityUniversity, hospital or other
- Study start
- Jul 2011
- Primary completion
- Sep 2015 (actual)
- Study completion
- Sep 2015 (actual)
- First posted
- 24 Dec 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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?
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm B | Experimental | Procedure: perioperative/Folfox + cetuximab12 weeks FOLFOX + cetuximab -> 4 weeks rest -> surgery -> 4-8 weeks rest -> 12 weeks FOLFOX + cetuximab |
| Arm A | Active comparator | Procedure: adjuvant surgery + FOLFOX + cetuximabsurgery -> 4-8 weeks rest -> 24 weeks FOLFOX + cetuximab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (23 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| adjuvant surgery + FOLFOX + cetuximabsurgery -> 4-8 weeks rest -> 24 weeks FOLFOX + cetuximab | Procedure or surgery | Arm A |
| perioperative/Folfox + cetuximab12 weeks FOLFOX + cetuximab -> 4 weeks rest -> surgery -> 4-8 weeks rest -> 12 weeks FOLFOX + cetuximab | Procedure or surgery | Arm B |
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.
1 secondary outcome
Secondary objectives
Time frame: 5 years
Results and safety
The study was stopped early (reason given: Recruitment difficulities). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Sep 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ulf P Neumann, Prof. study director
RWTH Aachen University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing adjuvant surgery + FOLFOX + cetuximab and perioperative/Folfox + cetuximab in people with Liver Metastasis, run by RWTH Aachen University at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 22 Sep 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: Recruitment difficulities). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clavien score (> grade 1) (time frame: 1 year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Sep 2015.