Nordic 8 - A Phase II Trial

• ClinicalTrials.gov Identifier: NCT01867697
• Recruitment Status: Completed
• First Posted: June 4, 2013
• Last Update Posted: October 30, 2020
• Sponsor: Per Pfeiffer
• Collaborator: Merck Serono International SA
• Information provided by (Responsible Party): Per Pfeiffer, Odense University Hospital

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Metastatic Colorectal Cancer	Drug: Cetuximab; Drug: Irinotecan; Drug: Oxaliplatin; Drug: Folinic Acid; Drug: Calcium Carbonate	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 173 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Potentially Resectable Metastatic Colorectal Cancer With Wild-type KRAS and BRAF: Alternating Chemotherapy Plus Cetuximab - A Randomised Phase II Trial
• Actual Study Start Date: May 2012
• Actual Primary Completion Date: March 2019
• Actual Study Completion Date: March 2019

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Biweekly cetuximab with continuously FOLFIRI; 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)	Drug: Cetuximab; Drug: Irinotecan; Drug: Folinic Acid; Drug: Calcium Carbonate
Experimental: Biweekly cetuximab with alternating FOLFIRI and mFOLFOX6; 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)	Drug: Cetuximab; Drug: Irinotecan; Drug: Oxaliplatin; Drug: Folinic Acid; Drug: Calcium Carbonate

Outcome Measures

Primary Outcome Measures :

1. Response rate (RR) [ Time Frame: March 2015 (up to 3 years) ]

Secondary Outcome Measures :

1. Survival (Overall survival) [ Time Frame: June 2016 (up to 5 years) ]
2. Frequency of secondary surgical resection (R0 + R1 + R2 resections) [ Time Frame: January 2015 (up to 3 years) ]
3. Frequency of secondary micro-radical surgical resection (R0 resection) [ Time Frame: March 2015 (up to 3 years) ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

Denmark

Aalborg University Hospital

Aalborg, Denmark, 9100

Aarhus University Hospital

Aarhus, Denmark, 8000

Rigshospitalet

Copenhagen, Denmark, 2100

Sydvestjysk Hospital

Esbjerg, Denmark, 6700

Herlev University Hospital

Herlev, Denmark, 2730

Herning Hospital

Herning, Denmark

Naestved Hospital

Naestved, Denmark, 4700

Odense University Hospital

Odense, Denmark, 5000

Roskilde Hospital

Roskilde, Denmark, 4000

Norway

Haukeland University Hospital

Bergen, Norway, 5021

Trondheim University Hospital

Trondheim, Norway

Sweden

Akademiska University Hospital

Uppsala, Sweden, 751 85

Sponsors and Collaborators

Per Pfeiffer

Merck Serono International SA

Investigators

• Principal Investigator: Per Pfeiffer, Professor, MD, PhD; Odense University Hospital
• Principal Investigator: Halfdan Sørbye, Professor, MD; Haukeland University Hospital
• Principal Investigator: Bengt Glimelius, Professor, MD; Akademiske Sygehus, Uppsala University

More Information

• Responsible Party: Per Pfeiffer, Professor, MD, PhD, Odense University Hospital
• ClinicalTrials.gov Identifier: NCT01867697
• Other Study ID Numbers: Nordic 8
• First Posted: June 4, 2013
• Last Update Posted: October 30, 2020
• Last Verified: October 2020

Additional relevant MeSH terms:

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Leucovorin; Folic Acid; Oxaliplatin; Irinotecan; Cetuximab; Calcium Carbonate; Levoleucovorin; Physiological Effects of Drugs; Antineoplastic Agents; Topoisomerase I Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents, Immunological; Antidotes; Protective Agents; Vitamin B Complex; Vitamins; Micronutrients