Clinical trial NCT01867697: Nordic 8 - A Phase II Trial
Official title: Potentially Resectable Metastatic Colorectal Cancer With Wild-type KRAS and BRAF: Alternating Chemotherapy Plus Cetuximab - A Randomised Phase II Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Colorectal Cancer
Lead sponsor: Odense University Hospital
Sponsor class: OTHER
Collaborators: name: Merck Serono International SA
First posted: 2013-06-04
Enrollment: 173
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: BASIC_SCIENCE

Brief 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.

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.


Eligibility criteria: Inclusion Criteria:

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
  * 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

Exclusion Criteria:

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
* 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

Primary outcomes:
measure: Response rate (RR)
timeFrame: March 2015 (up to 3 years)
Secondary outcomes:
measure: Survival (Overall survival)
timeFrame: June 2016 (up to 5 years)
measure: Frequency of secondary surgical resection (R0 + R1 + R2 resections)
timeFrame: January 2015 (up to 3 years)
measure: Frequency of secondary micro-radical surgical resection (R0 resection)
timeFrame: March 2015 (up to 3 years)
Other outcomes:
Locations:
city: Aalborg
country: Denmark
facility: Aalborg University Hospital
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Esbjerg
country: Denmark
facility: Sydvestjysk Hospital
city: Herlev
country: Denmark
facility: Herlev University Hospital
city: Herning
country: Denmark
facility: Herning Hospital
city: Naestved
country: Denmark
facility: Naestved Hospital
city: Odense
country: Denmark
facility: Odense University Hospital
city: Roskilde
country: Denmark
facility: Roskilde Hospital
city: Bergen
country: Norway
facility: Haukeland University Hospital
city: Trondheim
country: Norway
facility: Trondheim University Hospital
city: Uppsala
country: Sweden
facility: Akademiska University Hospital
Study officials:
affiliation: Odense University Hospital
name: Per Pfeiffer, Professor, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Haukeland University Hospital
name: Halfdan Sørbye, Professor, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Akademiske Sygehus, Uppsala University
name: Bengt Glimelius, Professor, MD
role: PRINCIPAL_INVESTIGATOR
References: