Nordic 8 - A Phase II Trial

Sponsor

Per Pfeiffer (Other)

Overall Status

Completed

CT.gov ID

NCT01867697

Collaborator

Merck Serono International SA (Industry)

173

Enrollment

Locations

Arms

Actual Duration (Months)

14.4

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

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

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 1, 2012

Actual Primary Completion Date :

Mar 1, 2019

Actual Study Completion Date :

Mar 1, 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

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

Response rate (RR) [March 2015 (up to 3 years)]

Secondary Outcome Measures

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)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Aalborg University Hospital	Aalborg	Denmark	9100
2	Aarhus University Hospital	Aarhus	Denmark	8000
3	Rigshospitalet	Copenhagen	Denmark	2100
4	Sydvestjysk Hospital	Esbjerg	Denmark	6700
5	Herlev University Hospital	Herlev	Denmark	2730
6	Herning Hospital	Herning	Denmark
7	Naestved Hospital	Naestved	Denmark	4700
8	Odense University Hospital	Odense	Denmark	5000
9	Roskilde Hospital	Roskilde	Denmark	4000
10	Haukeland University Hospital	Bergen	Norway	5021
11	Trondheim University Hospital	Trondheim	Norway
12	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