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Nordic 8 - A Phase II Trial

Primary Purpose

Metastatic Colorectal Cancer

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Cetuximab
Irinotecan
Oxaliplatin
Folinic Acid
Calcium Carbonate
Sponsored by
Per Pfeiffer
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Metastatic Colorectal Cancer

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Aalborg University Hospital
  • Aarhus University Hospital
  • Rigshospitalet
  • Sydvestjysk Hospital
  • Herlev University Hospital
  • Herning Hospital
  • Naestved Hospital
  • Odense University Hospital
  • Roskilde Hospital
  • Haukeland University Hospital
  • Trondheim University Hospital
  • Akademiska University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Biweekly cetuximab with continuously FOLFIRI

Biweekly cetuximab with alternating FOLFIRI and mFOLFOX6

Arm Description

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)

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)

Outcomes

Primary Outcome Measures

Response rate (RR)

Secondary Outcome Measures

Survival (Overall survival)
Frequency of secondary surgical resection (R0 + R1 + R2 resections)
Frequency of secondary micro-radical surgical resection (R0 resection)

Full Information

First Posted
June 21, 2012
Last Updated
October 29, 2020
Sponsor
Per Pfeiffer
Collaborators
Merck Serono International SA
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1. Study Identification

Unique Protocol Identification Number
NCT01867697
Brief Title
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

2. Study Status

Record Verification Date
October 2020
Overall Recruitment Status
Completed
Study Start Date
May 2012 (Actual)
Primary Completion Date
March 2019 (Actual)
Study Completion Date
March 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Per Pfeiffer
Collaborators
Merck Serono International SA

4. Oversight

Data Monitoring Committee
No

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Colorectal Cancer

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 2
Interventional Study Model
Factorial Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
173 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Biweekly cetuximab with continuously FOLFIRI
Arm Type
Active Comparator
Arm Description
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)
Arm Title
Biweekly cetuximab with alternating FOLFIRI and mFOLFOX6
Arm Type
Experimental
Arm Description
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)
Intervention Type
Drug
Intervention Name(s)
Cetuximab
Intervention Type
Drug
Intervention Name(s)
Irinotecan
Intervention Type
Drug
Intervention Name(s)
Oxaliplatin
Intervention Type
Drug
Intervention Name(s)
Folinic Acid
Intervention Type
Drug
Intervention Name(s)
Calcium Carbonate
Primary Outcome Measure Information:
Title
Response rate (RR)
Time Frame
March 2015 (up to 3 years)
Secondary Outcome Measure Information:
Title
Survival (Overall survival)
Time Frame
June 2016 (up to 5 years)
Title
Frequency of secondary surgical resection (R0 + R1 + R2 resections)
Time Frame
January 2015 (up to 3 years)
Title
Frequency of secondary micro-radical surgical resection (R0 resection)
Time Frame
March 2015 (up to 3 years)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Per Pfeiffer, Professor, MD, PhD
Organizational Affiliation
Odense University Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Halfdan Sørbye, Professor, MD
Organizational Affiliation
Haukeland University Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Bengt Glimelius, Professor, MD
Organizational Affiliation
Akademiske Sygehus, Uppsala University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Aalborg University Hospital
City
Aalborg
ZIP/Postal Code
9100
Country
Denmark
Facility Name
Aarhus University Hospital
City
Aarhus
ZIP/Postal Code
8000
Country
Denmark
Facility Name
Rigshospitalet
City
Copenhagen
ZIP/Postal Code
2100
Country
Denmark
Facility Name
Sydvestjysk Hospital
City
Esbjerg
ZIP/Postal Code
6700
Country
Denmark
Facility Name
Herlev University Hospital
City
Herlev
ZIP/Postal Code
2730
Country
Denmark
Facility Name
Herning Hospital
City
Herning
Country
Denmark
Facility Name
Naestved Hospital
City
Naestved
ZIP/Postal Code
4700
Country
Denmark
Facility Name
Odense University Hospital
City
Odense
ZIP/Postal Code
5000
Country
Denmark
Facility Name
Roskilde Hospital
City
Roskilde
ZIP/Postal Code
4000
Country
Denmark
Facility Name
Haukeland University Hospital
City
Bergen
ZIP/Postal Code
5021
Country
Norway
Facility Name
Trondheim University Hospital
City
Trondheim
Country
Norway
Facility Name
Akademiska University Hospital
City
Uppsala
ZIP/Postal Code
751 85
Country
Sweden

12. IPD Sharing Statement

Learn more about this trial

Nordic 8 - A Phase II Trial

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