Colorectal CancerPhase 2NCT01384994
Panitumumab After Resection of Liver Metastases From Colorectal Cancer in KRAS Wild-type Patients
A Phase 2 study testing Folic Acid, 5-FU and Oxaliplatin in people with Colorectal Cancer and KRAS Wildtype, run by PD Dr. med. Volker Heinemann at 1 site in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer, KRAS Wildtype, After Resection of Liver Metastases
- What is being tested?
- Folic Acid, 5-FU and Oxaliplatin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 111 participants
- Where
- 1 siteGermany
- Study dates
- Aug 2011to Aug 2014
- Phase
- Phase 2
- 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
- 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
Who cannot join
- 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
Show all 31Show fewer
- 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
- Hepatic: Albumin >= 2.5 g/dL, Serum bilirubin <= 2 mg/dL, AST and ALT <= 3 x ULN
- Renal: Serum Creatinine <= 1.5 mg/dL
- 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.
- Requires concurrent cancer therapy (chemotherapy, radiation therapy, biologic therapy, immunotherapy, or hormonal therapy) while on study.
- Requires concurrent treatment with an investigational agent, participation in another clinical trial, or any specifically prohibited medication while on study.
- Has a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to 5-fluorouracil, folinic acid, oxaliplatin, or panitumumab.
- Other active malignancy
- Known alcohol abuse or drug addiction
- Incapability to give informed consent
Trial locations and contacts
1 site in 1 country.
Germany1 site, 1 recruiting
- Recruiting
Ludwig-Maximilians - University of Munich
Munich, 81377
Volker Heinemann, Prof. Dr. med., +49 89 7095 ext. 0, volker.heinemann@med.uni-muenchen.de
Clemens Giessen, Dr. med., +49 89 7095 ext. 0, clemens.giessen@med.uni-muenchen.de
About this study
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.
Read more
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.
- Being tested
- Folic Acid, 5-FU, Oxaliplatin, Panitumumab
- Keywords
- Colorectal Cancer, PARLIM, KRAS Wildtype, Liver metastases
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Folic AcidDrug
400 mg/m2, 2h infusion, d1, q2w
5-FUDrug
400 mg/m2 bolus iv, d1, q2w
5-FUDrug
2400 mg/m2 46-h infusion, d1-2, q2w
OxaliplatinDrug
85 mg/m2 d1, q2w
PanitumumabDrug
6 mg/kg BW every 2 weeks
PanitumumabDrug
Panitumumab maintenance phase (3 months) 9mg/kg BW every 3 weeks
Folic AcidDrug
400 mg/m2, 2-h infusion, d1, q2w
5-FUDrug
400 mg/m2 bolus iv, d1, q2w
5-FUDrug
2400 mg/m2 46-h infusion, d1-2, q2w
OxaliplatinDrug
85 mg/m2 d1, q2w
| Study group | Role | What they receive |
|---|---|---|
| FOLFOX + Panitumumab | Experimental | Not described Receives: Drug: Folic Acid; Drug: 5-FU; Drug: Oxaliplatin; Drug: Panitumumab |
| FOLFOX | Active comparator | Not described Receives: Drug: Folic Acid; Drug: 5-FU; Drug: Oxaliplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression Free Survival
Measured: 2 years after randomisation
Secondary outcomes (2)
Tolerability and side effects
Measured: approximate 6 months after randomisation
Overall Survival
Measured: 2 years after randomisation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jun 2011 (estimated)
- Study startAug 2011
- Primary completionAug 2013 (estimated)
- Study completionAug 2014 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Colorectal CancerStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 111 participants (estimated)
Sponsor and investigators
- Lead sponsor
- PD Dr. med. Volker Heinemann
- Sponsor type
- University, hospital or other
- Collaborators
- Amgen
- Responsible party
- Sponsor-investigator, PD Dr. med. Volker Heinemann, Ludwig-Maximilians - University of Munich
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01384994
- Sponsor's protocol ID
- PARLIM
- Status last verified
- Jul 2012
- First submitted
- 2 May 2011
- Last updated
- 9 Jul 2012
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 35970102
Study at a glance
From the registry record, last updated by the sponsor on 9 Jul 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Panitumumab After Resection of Liver Metastases From Colorectal Cancer in KRAS Wild-type Patients
- ClinicalTrials.gov ID
- NCT01384994
- Acronym / sponsor ID
- PARLIM
- Keywords
- Colorectal Cancer, PARLIM, KRAS Wildtype, Liver metastases
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 111 participants (estimated)
- Lead sponsor
- PD Dr. med. Volker HeinemannUniversity, hospital or other
- Collaborators
- Amgen
- Study start
- Aug 2011
- Primary completion
- Aug 2013 (estimated)
- Study completion
- Aug 2014 (estimated)
- First posted
- 29 Jun 2011 (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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| FOLFOX + Panitumumab | Experimental | Drug: Folic Acid, Drug: 5-FU, Drug: Oxaliplatin, Drug: Panitumumab |
| FOLFOX | Active comparator | Drug: Folic Acid, Drug: 5-FU, Drug: Oxaliplatin |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (31 listed)
- 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%)
- Adequate organ function as defined by Table 1:
- Known manifestations of metastatic disease
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 |
|---|---|---|
| Folic Acid400 mg/m2, 2h infusion, d1, q2w | Drug | FOLFOX + Panitumumab |
| 5-FU400 mg/m2 bolus iv, d1, q2w | Drug | FOLFOX + Panitumumab |
| 5-FU2400 mg/m2 46-h infusion, d1-2, q2w | Drug | FOLFOX + Panitumumab |
| Oxaliplatin85 mg/m2 d1, q2w | Drug | FOLFOX + Panitumumab |
| Panitumumab6 mg/kg BW every 2 weeks | Drug | FOLFOX + Panitumumab |
| PanitumumabPanitumumab maintenance phase (3 months) 9mg/kg BW every 3 weeks | Drug | FOLFOX + Panitumumab |
| Folic Acid400 mg/m2, 2-h infusion, d1, q2w | Drug | FOLFOX |
| 5-FU400 mg/m2 bolus iv, d1, q2w | Drug | FOLFOX |
| 5-FU2400 mg/m2 46-h infusion, d1-2, q2w | Drug | FOLFOX |
| Oxaliplatin85 mg/m2 d1, q2w | Drug | FOLFOX |
Primary outcome
Progression Free Survival
Time frame: 2 years after randomisation
2 secondary outcomes
Tolerability and side effects
Time frame: approximate 6 months after randomisation
Overall Survival
Time frame: 2 years after randomisation
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jul 2012.
- Derived from this study: PubMed 35970102Modest 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.
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Folic Acid, 5-FU and Oxaliplatin in people with Colorectal Cancer and KRAS Wildtype, run by PD Dr. med. Volker Heinemann 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 7 inclusion and 31 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: status not confirmed, as of the sponsor's last update on 9 Jul 2012. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Volker Heinemann, Prof. Dr. med. (+49 89 7095 ext. 0, volker.heinemann@med.uni-muenchen.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression Free Survival (time frame: 2 years after randomisation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01384994, which also lists 1 linked publication.
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 9 Jul 2012.