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Nordic 8 - A Phase II Trial

Phase 2
Completed
Conditions
Metastatic Colorectal Cancer
Interventions
Registration Number
NCT01867697
Lead Sponsor
Per Pfeiffer
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
173
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
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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
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Study & Design

Study Type
INTERVENTIONAL
Study Design
FACTORIAL
Arm && Interventions
GroupInterventionDescription
Biweekly cetuximab with alternating FOLFIRI and mFOLFOX6IrinotecanBiweekly 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)
Biweekly cetuximab with continuously FOLFIRICetuximabBiweekly 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 mFOLFOX6CetuximabBiweekly 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)
Biweekly cetuximab with continuously FOLFIRIIrinotecanBiweekly 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 continuously FOLFIRICalcium 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 continuously FOLFIRIFolinic AcidBiweekly 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 mFOLFOX6OxaliplatinBiweekly 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)
Biweekly cetuximab with alternating FOLFIRI and mFOLFOX6Folinic AcidBiweekly 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)
Biweekly cetuximab with alternating FOLFIRI and mFOLFOX6Calcium 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)
Primary Outcome Measures
NameTimeMethod
Response rate (RR)March 2015 (up to 3 years)
Secondary Outcome Measures
NameTimeMethod
Frequency of secondary surgical resection (R0 + R1 + R2 resections)January 2015 (up to 3 years)
Survival (Overall survival)June 2016 (up to 5 years)
Frequency of secondary micro-radical surgical resection (R0 resection)March 2015 (up to 3 years)

Trial Locations

Locations (12)

Rigshospitalet

🇩🇰

Copenhagen, Denmark

Sydvestjysk Hospital

🇩🇰

Esbjerg, Denmark

Odense University Hospital

🇩🇰

Odense, Denmark

Aalborg University Hospital

🇩🇰

Aalborg, Denmark

Aarhus University Hospital

🇩🇰

Aarhus, Denmark

Herlev University Hospital

🇩🇰

Herlev, Denmark

Herning Hospital

🇩🇰

Herning, Denmark

Naestved Hospital

🇩🇰

Naestved, Denmark

Roskilde Hospital

🇩🇰

Roskilde, Denmark

Haukeland University Hospital

🇳🇴

Bergen, Norway

Trondheim University Hospital

🇳🇴

Trondheim, Norway

Akademiska University Hospital

🇸🇪

Uppsala, Sweden

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