Metastatic Colorectal CancerPhase 2NCT01867697
Nordic 8 - A Phase II Trial
A Phase 2 study testing Cetuximab, Irinotecan and Oxaliplatin in people with Metastatic Colorectal Cancer, run by Per Pfeiffer at 12 sites in 3 countries.
Trial summary
Nordic randomized phase II trial which evaluates whether biweekly cetuximab with alternating FOLFIRI and mFOLFOX6 is more effective than biweekly cetuximab with continuously FOLFIRI in patients with potential resectable KRAS wildtype metastatic colorectal cancer. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Metastatic Colorectal Cancer
- What is being tested?
- Cetuximab, Irinotecan and Oxaliplatin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 173 participants
- Where
- 12 sitesin 3 countries
- Study dates
- May 2012to Mar 2019
- 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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histology and stages:
- Histologically proven adenocarcinoma in the colon or rectum
- At least 1 measurable metastatic disease manifestation according to the RECIST criteria (version 1.1)
- Potentially completely resectable or potentially curable metastatic colorectal cancer as determined by the local MDT conference and that requires tumour shrinkage before resection is possible. The following definitions are indicative:
- 4 or more liver metastases (CRLeM) without extra-hepatic disease
- 2 or more lung metastases (CRLuM) without hepatic or extra-hepatic disease
Show all 18Show fewer
- 1 or more CRLeM determined as "potentially resectable" (such as because of location) by the local MDT.
- 1 or more CRLuM determined by the local MDT as potentially resectable (such as because of location).
- Non-resectable primary disease with resectable CRLeM or CRLuM.
- KRAS and BRAF status:
- Tumour tissue (primary or metastasis) typed as wild-type KRAS AND wild-type BRAF
- General conditions:
- age > 18 years
- WHO performance status ≤ 1
- expected survival > 3 months
- sufficient bone-marrow function (Hb ≥ 6.2 µmol/l/Hb > 10 g/dl ANC ≥ 1.5 x 109/l, thrombocytes ≥ 100 x 109/l)
- sufficient kidney and liver function: total bilirubin ≤ 1.5 x upper normal limit, serum creatinine ≤ 1.25 x upper normal limit, ALAT ≤ 3 x upper normal limit and ≤ 5 x upper normal limit with liver metastases
- the patient must have signed an informed declaration of consent before being registered; this must be documentable according to national guidelines
Who cannot join
- Previous treatment:
- previous chemotherapy for advanced/metastatic disease
- adjuvant chemotherapy unless completed more than 6 months before registration
- previous treatment with oxaliplatin or irinotecan
- previous treatment with cetuximab or other treatment for EGFR
- History of Inflammatory Bowel disease
Show all 10Show fewer
- Severe or uncontrolled cardiovascular disease, congestive heart failure NYHA III or IV, unstable angina pectoris, history of myocardial infarction within the last twelve months, significant arrhythmias)
- Any condition that, according to the treating physician's judgement, could prevent the planned medical/surgical treatment from being carried out responsibly (such as uncontrolled active infection, known hypersensitivity or contra-indication for the planned treatment.
- Pregnant or breast-feeding women
- Patients of fertile age who do not want to use reliable contraception
Trial locations and contacts
12 sites in 3 countries.
12 sites in 3 countries
Denmark9 sites
Aalborg University Hospital
Aalborg, 9100
Aarhus University Hospital
Aarhus, 8000
Rigshospitalet
Copenhagen, 2100
Sydvestjysk Hospital
Esbjerg, 6700
Herlev University Hospital
Herlev, 2730
Herning Hospital
Herning
Naestved Hospital
Næstved, 4700
Odense University Hospital
Odense, 5000
Roskilde Hospital
Roskilde, 4000
Norway2 sites
Haukeland University Hospital
Bergen, 5021
Trondheim University Hospital
Trondheim
About this study
Official title: Potentially Resectable Metastatic Colorectal Cancer With Wild-type KRAS and BRAF: Alternating Chemotherapy Plus Cetuximab - A Randomised Phase II Trial
Nordic randomized phase II trial which evaluates whether biweekly cetuximab with alternating FOLFIRI and mFOLFOX6 is more effective than biweekly cetuximab with continuously FOLFIRI in patients with potential resectable KRAS wildtype metastatic colorectal cancer.
All patients will be randomized to biweekly cetuximab 500 mg/m2 in combination with arm A) FOLFIRI (irinotecan 180 mg/m2 IV, leucovorin: 400 mg/m2 IV, 5FU bolus: 400 mg/m2 IV and 46 hours 5FU infusion of 2400 mg/m2 every 2 weeks) or arm B) FOLFIRI alternating with FOLFOX6 (Oxaliplatin: 85 mg/m2 IV, leucovorin: 400 mg/m2 IV, 5FU bolus: 400 mg/m2 IV and 46 hours 5FU infusion of 2400 mg/m2 every 2 weeks) .
Read more
Primary objective: response rate (RECIST 1.1) in patients with with potential resectable KRAS wildtype metastatic colorectal cancer.
Secondary objectives: Resection rate, PFS, OS, Quality of life, tolerability. Biomarker evaluation to measure plasma biomarkers, Tumour blocks and sequential serum and plasma will be collected to search for markers that may predict efficacy including respectability and safety.
- Conditions
- Metastatic Colorectal Cancer
- Being tested
- Cetuximab, Irinotecan, Oxaliplatin, Folinic Acid, Calcium Carbonate
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CetuximabDrug
IrinotecanDrug
OxaliplatinDrug
Folinic AcidDrug
Calcium CarbonateDrug
| Study group | Role | What they receive |
|---|---|---|
| Biweekly cetuximab with continuously FOLFIRI | Active comparator | Biweekly cetuximab 500 mg/m2 in combination with FOLFIRI (irinotecan 180 mg/m2 IV, leucovorin: 400 mg/m2 IV, 5FU bolus: 400 mg/m2 IV and 46 hours 5FU infusion of 2400 mg/m2 every 2 weeks) Receives: Drug: Cetuximab; Drug: Irinotecan; Drug: Folinic Acid; Drug: Calcium Carbonate |
| Biweekly cetuximab with alternating FOLFIRI and mFOLFOX6 | Experimental | Biweekly cetuximab 500 mg/m2 in combination with FOLFIRI alternating with FOLFOX6 (Oxaliplatin: 85 mg/m2 IV, leucovorin: 400 mg/m2 IV, 5FU bolus: 400 mg/m2 IV and 46 hours 5FU infusion of 2400 mg/m2 every 2 weeks) Receives: Drug: Cetuximab; Drug: Irinotecan; Drug: Oxaliplatin; Drug: Folinic Acid; Drug: Calcium Carbonate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response rate (RR)
Measured: March 2015 (up to 3 years)
Secondary outcomes (3)
Survival (Overall survival)
Measured: June 2016 (up to 5 years)
Frequency of secondary surgical resection (R0 + R1 + R2 resections)
Measured: January 2015 (up to 3 years)
Frequency of secondary micro-radical surgical resection (R0 resection)
Measured: March 2015 (up to 3 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2013 (estimated)
- Study startMay 2012
- Primary completionMar 2019
- Study completionMar 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic 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
- Basic science
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Enrolment
- 173 participants (actual)
Sponsor and investigators
- Lead sponsor
- Per Pfeiffer
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Serono International SA
- Responsible party
- Sponsor-investigator, Per Pfeiffer, Odense University Hospital
- Investigators
- Per Pfeiffer, Professor, MD, PhD, Principal investigator, Odense University HospitalHalfdan Sørbye, Professor, MD, Principal investigator, Haukeland University HospitalBengt Glimelius, Professor, MD, Principal investigator, Akademiske Sygehus, Uppsala University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01867697
- Sponsor's protocol ID
- Nordic 8
- Status last verified
- Oct 2020
- First submitted
- 21 Jun 2012
- Last updated
- 30 Oct 2020
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Potentially Resectable Metastatic Colorectal Cancer With Wild-type KRAS and BRAF: Alternating Chemotherapy Plus Cetuximab - A Randomised Phase II Trial
- ClinicalTrials.gov ID
- NCT01867697
- Acronym / sponsor ID
- Nordic 8
- Conditions
- Metastatic Colorectal Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 173 participants (actual)
- Lead sponsor
- Per PfeifferUniversity, hospital or other
- Collaborators
- Merck Serono International SA
- Study start
- May 2012 (actual)
- Primary completion
- Mar 2019 (actual)
- Study completion
- Mar 2019 (actual)
- First posted
- 4 Jun 2013 (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.
Nordic randomized phase II trial which evaluates whether biweekly cetuximab with alternating FOLFIRI and mFOLFOX6 is more effective than biweekly cetuximab with continuously FOLFIRI in patients with potential resectable KRAS wildtype metastatic colorectal cancer.
All patients will be randomized to biweekly cetuximab 500 mg/m2 in combination with arm A) FOLFIRI (irinotecan 180 mg/m2 IV, leucovorin: 400 mg/m2 IV, 5FU bolus: 400 mg/m2 IV and 46 hours 5FU infusion of 2400 mg/m2 every 2 weeks) or arm B) FOLFIRI alternating with FOLFOX6 (Oxaliplatin: 85 mg/m2 IV, leucovorin: 400 mg/m2 IV, 5FU bolus: 400 mg/m2 IV and 46 hours 5FU infusion of 2400 mg/m2 every 2 weeks) .
Primary objective: response rate (RECIST 1.1) in patients with with potential resectable KRAS wildtype metastatic colorectal cancer.
Secondary objectives: Resection rate, PFS, OS, Quality of life, tolerability. Biomarker evaluation to measure plasma biomarkers, Tumour blocks and sequential serum and plasma will be collected to search for markers that may predict efficacy including respectability and safety.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Biweekly cetuximab with continuously FOLFIRI | Active comparator | Drug: Cetuximab, Drug: Irinotecan, Drug: Folinic Acid, Drug: Calcium CarbonateBiweekly cetuximab 500 mg/m2 in combination with FOLFIRI (irinotecan 180 mg/m2 IV, leucovorin: 400 mg/m2 IV, 5FU bolus: 400 mg/m2 IV and 46 hours 5FU infusion of 2400 mg/m2 every 2 weeks) |
| Biweekly cetuximab with alternating FOLFIRI and mFOLFOX6 | Experimental | Drug: Cetuximab, Drug: Irinotecan, Drug: Oxaliplatin, Drug: Folinic Acid, Drug: Calcium CarbonateBiweekly cetuximab 500 mg/m2 in combination with FOLFIRI alternating with FOLFOX6 (Oxaliplatin: 85 mg/m2 IV, leucovorin: 400 mg/m2 IV, 5FU bolus: 400 mg/m2 IV and 46 hours 5FU infusion of 2400 mg/m2 every 2 weeks) |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Histologically proven adenocarcinoma in the colon or rectum
- At least 1 measurable metastatic disease manifestation according to the RECIST criteria (version 1.1)
- Potentially completely resectable or potentially curable metastatic colorectal cancer as determined by the local MDT conference and that requires tumour shrinkage before resection is possible. The following definitions are indicative:
- Tumour tissue (primary or metastasis) typed as wild-type KRAS AND wild-type BRAF
- age > 18 years
Key exclusion criteria (10 listed)
- previous chemotherapy for advanced/metastatic disease
- adjuvant chemotherapy unless completed more than 6 months before registration
- previous treatment with oxaliplatin or irinotecan
- previous treatment with cetuximab or other treatment for EGFR
- History of Inflammatory Bowel 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 |
|---|---|---|
| Cetuximab | Drug | Biweekly cetuximab with alternating FOLFIRI and mFOLFOX6, Biweekly cetuximab with continuously FOLFIRI |
| Irinotecan | Drug | Biweekly cetuximab with alternating FOLFIRI and mFOLFOX6, Biweekly cetuximab with continuously FOLFIRI |
| Oxaliplatin | Drug | Biweekly cetuximab with alternating FOLFIRI and mFOLFOX6 |
| Folinic Acid | Drug | Biweekly cetuximab with alternating FOLFIRI and mFOLFOX6, Biweekly cetuximab with continuously FOLFIRI |
| Calcium Carbonate | Drug | Biweekly cetuximab with alternating FOLFIRI and mFOLFOX6, Biweekly cetuximab with continuously FOLFIRI |
Primary outcome
Response rate (RR)
Time frame: March 2015 (up to 3 years)
3 secondary outcomes
Survival (Overall survival)
Time frame: June 2016 (up to 5 years)
Frequency of secondary surgical resection (R0 + R1 + R2 resections)
Time frame: January 2015 (up to 3 years)
Frequency of secondary micro-radical surgical resection (R0 resection)
Time frame: March 2015 (up to 3 years)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Oct 2020.
Related trials for Metastatic Colorectal Cancer
RecruitingPhase 1/2
A Phase 1 and 2 Study of VMD-102 in Hepatocellular Carcinoma and Other Solid Tumors
Hepatocellular Carcinoma (HCC), Metastatic Uveal Melanoma
Not yet recruitingPhase 1
Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy
Colorectal Neoplasms, Neoplasms
RecruitingPhase 3
Study of Petosemtamab Plus Chemotherapy Versus Cetuximab Plus Chemotherapy in RAS and BRAF Wild-type, Unresectable or Metastatic, Left-sided Colorectal Cancer (LiGeR-CRC1)
Left-sided Colorectal Cancer
Not yet recruitingPhase 3
GFH375 Plus Cetuximab vs Investigator's Choice of Treatment in KRAS G12D-Mutant Refractory Metastatic Colorectal Cancer
Colorectal Cancer
RecruitingPhase 1
This is a Phase 1/1b Study to Evaluate the Safety and Preliminary Antitumor Activity of LTZ-232 in Participants With Advanced/Metastatic Colorectal Cancer and Other Solid Tumors
Colorectal Cancer, Advanced/Metastatic Solid Tumor
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.
Per Pfeiffer, Professor, MD, PhD principal investigator
Odense University Hospital
Halfdan Sørbye, Professor, MD principal investigator
Haukeland University Hospital
Bengt Glimelius, Professor, MD principal investigator
Akademiske Sygehus, Uppsala University
12 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Cetuximab, Irinotecan and Oxaliplatin in people with Metastatic Colorectal Cancer, run by Per Pfeiffer at 12 sites in 3 countries.
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 18 inclusion and 10 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: finished, as of the sponsor's last update on 30 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in Denmark, Norway, Sweden. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Response rate (RR) (time frame: March 2015 (up to 3 years)). 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 30 Oct 2020.