Nordic 8 - A Phase II Trial

NCT ID: NCT01867697

Last Updated: 2020-10-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

173 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-05-31

Study Completion Date

2019-03-31

Brief Summary

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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

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Conditions

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Metastatic Colorectal Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

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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)

Group Type ACTIVE_COMPARATOR

Cetuximab

Intervention Type DRUG

Irinotecan

Intervention Type DRUG

Folinic Acid

Intervention Type DRUG

Calcium Carbonate

Intervention Type DRUG

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)

Group Type EXPERIMENTAL

Cetuximab

Intervention Type DRUG

Irinotecan

Intervention Type DRUG

Oxaliplatin

Intervention Type DRUG

Folinic Acid

Intervention Type DRUG

Calcium Carbonate

Intervention Type DRUG

Interventions

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Cetuximab

Intervention Type DRUG

Irinotecan

Intervention Type DRUG

Oxaliplatin

Intervention Type DRUG

Folinic Acid

Intervention Type DRUG

Calcium Carbonate

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merck Serono International SA

INDUSTRY

Sponsor Role collaborator

Per Pfeiffer

OTHER

Sponsor Role lead

Responsible Party

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Per Pfeiffer

Professor, MD, PhD

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Per Pfeiffer, Professor, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Odense University Hospital

Halfdan Sørbye, Professor, MD

Role: PRINCIPAL_INVESTIGATOR

Haukeland University Hospital

Bengt Glimelius, Professor, MD

Role: PRINCIPAL_INVESTIGATOR

Akademiske Sygehus, Uppsala University

Locations

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Aalborg University Hospital

Aalborg, , Denmark

Site Status

Aarhus University Hospital

Aarhus, , Denmark

Site Status

Rigshospitalet

Copenhagen, , Denmark

Site Status

Sydvestjysk Hospital

Esbjerg, , Denmark

Site Status

Herlev University Hospital

Herlev, , Denmark

Site Status

Herning Hospital

Herning, , Denmark

Site Status

Naestved Hospital

Næstved, , Denmark

Site Status

Odense University Hospital

Odense, , Denmark

Site Status

Roskilde Hospital

Roskilde, , Denmark

Site Status

Haukeland University Hospital

Bergen, , Norway

Site Status

Trondheim University Hospital

Trondheim, , Norway

Site Status

Akademiska University Hospital

Uppsala, , Sweden

Site Status

Countries

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Denmark Norway Sweden

Other Identifiers

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Nordic 8

Identifier Type: -

Identifier Source: org_study_id