Nordic 8 - A Phase II Trial

Per Pfeiffer

Status and phase: Completed; Phase 2

Conditions: Metastatic Colorectal Cancer

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

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01867697

Nordic 8

Details and patient eligibility

About

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.

Enrollment: 173 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No 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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: None (Open label)

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173 participants in 2 patient groups

Biweekly cetuximab with continuously FOLFIRI

Active Comparator group

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)

Treatment:

Drug: Calcium Carbonate

Drug: Cetuximab

Drug: Irinotecan

Drug: Folinic Acid

Biweekly cetuximab with alternating FOLFIRI and mFOLFOX6

Experimental group

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)

Treatment:

Drug: Calcium Carbonate

Drug: Cetuximab

Drug: Irinotecan

Drug: Oxaliplatin

Drug: Folinic Acid