Nordic 8 - A Phase II Trial

NCT01867697 | Completed Phase 2

• 1 other identifier: Nordic 8
• Study Type: interventional
• Target: 173
• Locations: 3 countries
• Sites: 12

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.

Conditions

Metastatic Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• Response rate (RR)

  March 2015 (up to 3 years)

Secondary Outcomes (3)

• Survival (Overall survival)

  June 2016 (up to 5 years)

• Frequency of secondary surgical resection (R0 + R1 + R2 resections)

  January 2015 (up to 3 years)

• Frequency of secondary micro-radical surgical resection (R0 resection)

  March 2015 (up to 3 years)

Study Arms (2)

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)

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)

Drug: Cetuximab; Drug: Irinotecan; Drug: Oxaliplatin; Drug: Folinic Acid; Drug: Calcium Carbonate

Interventions

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

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• or more liver metastases (CRLeM) without extra-hepatic disease
• or more lung metastases (CRLuM) without hepatic or extra-hepatic disease
• or more CRLeM determined as "potentially resectable" (such as because of location) by the local MDT.
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Per Pfeiffer: lead
• Merck Serono International SA: collaborator

Study Sites (12)

Aalborg University Hospital

Aalborg, 9100, Denmark

Location

Aarhus University Hospital

Aarhus, 8000, Denmark

Location

Rigshospitalet

Copenhagen, 2100, Denmark

Location

Sydvestjysk Hospital

Esbjerg, 6700, Denmark

Location

Herlev University Hospital

Herlev, 2730, Denmark

Location

Herning Hospital

Herning, Denmark

Location

Naestved Hospital

Næstved, 4700, Denmark

Location

Odense University Hospital

Odense, 5000, Denmark

Location

Roskilde Hospital

Roskilde, 4000, Denmark

Location

Haukeland University Hospital

Bergen, 5021, Norway

Location

Trondheim University Hospital

Trondheim, Norway

Location

Akademiska University Hospital

Uppsala, 751 85, Sweden

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Cetuximab; Irinotecan; Oxaliplatin; Leucovorin; Calcium Carbonate

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Camptothecin; Alkaloids; Heterocyclic Compounds; Coordination Complexes; Organic Chemicals; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Calcium Compounds; Inorganic Chemicals; Carbonates; Carbonic Acid; Carbon Compounds, Inorganic; Minerals

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, MD, PhD

Study Record Dates

• First Submitted: June 21, 2012
• First Posted: June 4, 2013
• Study Start: May 1, 2012
• Primary Completion: March 1, 2019
• Study Completion: March 1, 2019
• Last Updated: October 30, 2020

Record last verified: 2020-10

Locations

NO (2); DK (9); SE (1)