A two arm phase II study of FOLFIRI in combination with standard or escalating dose of cetuximab as first line treatment of K-Ras wild type metastatic colorectal cancer: Everest 2 - Everest 2

Phase 1

• Conditions: K-Ras wild type metastatic colorectal cancer; MedDRA version: 12.1Level: LLTClassification code 10052358Term: Colorectal cancer metastatic

• Registration Number: EUCTR2009-009992-36-BE
• Lead Sponsor: niversity Hospital Leuven

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-09-10
• Last Update Posted: 8 August 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 375

Inclusion Criteria

1. Written informed consent (+ optional for PK and TR) must be given according to ICH/GCP and national/local regulations.
2. Patient is at least 18 years of age.
3. Patient’s body weight is = 120 kg.
4. Histologically proven and measurable (RECIST criteria v.1.1) metastatic adenocarcinoma of the colon or rectum, not in a previously irradiated area.
5. K-Ras wild type tumour eligible for treatment with cetuximab.
6. Unresectable metastatic disease.
7. Life expectancy of at least 12 weeks.
8. WHO ECOG performance status: 0 or 1.
9. Effective contraception for both male and female patients if the risk of conception exists.
10. Adequate organ function.
11. Adequate bone marrow, hepatic and renal function (assessed within 14 days prior to study entry):
- Hemoglobin >10.0 g/dL, absolute neutrophil count > 1.5 x 109/L, platelet count > 100 x 109/L
- ALAT, ASAT < 2.5 x ULN, up to < 5 x ULN in case of liver metastases
- Alkaline phosphatase < 2.5 x ULN
- Total bilirubin < 1.5 x ULN
- Creatinine clearance > 50 mL/min (calculated according to Cockroft and Gault)

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Prior treatment for metastatic disease (adjuvant therapy with fluoropyrimidines +/-oxaliplatin based regimens allowed if stopped 6 months prior to registration on study).
2. Prior treatment with EGFR inhibitor or chemotherapy with irinotecan in adjuvant settings.
3. Surgery (excluding diagnostic biopsy) or irradiation within 4 weeks prior to study entry.
4. Administration of any investigational drug or agent/procedure, i.e. participation in another trial within 4 weeks before beginning treatment.
5. Concurrent chronic systemic immune therapy, chemotherapy, radiation therapy or hormone therapy not indicated in the study protocol.
6. Any active dermatological condition > grade 1.
7. Brain metastasis (known or suspected).
8. Significant impairment of intestinal absorption (e.g. chronic diarrhea, inflammatory bowel disease).
9. Other uncontrolled concomitant illness, including serious uncontrolled intercurrent infection.
10. Uncontrolled coronary artery disease and/or unstable angina, a history of a myocardial infarction within the last 12 months or heart failure NYHA class III or IV. High risk of uncontrolled arrhythmia.
11. Known allergy or any other adverse reaction to any of the drugs or to any related compound.
12. Known dihydropyrimidine dehydrogenase (DPD) deficiency.
13. Gilbert disease.
14. Previous (within 5 years) or concurrent malignancies at other sites with the exception of surgically cured or adequately treated carcinoma in-situ of the cervix and basal cell carcinoma of the skin.
15. Organ allografts requiring immunosuppressive therapy.
16. Pregnancy (absence confirmed by serum/urine beta human choriongonadotrophin in pre-menopausal women) or breast-feeding.
17. Medical, social or psychological condition which, in the opinion of the investigator, would not permit the patient to complete the study or sign meaningful informed consent.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To provide a precise estimate (+/- 10%) of the progression-free survival (PFS) rate at 9 months, in patients without skin toxicity at 3 weeks (according to NCI CTCAE v. 4.0), treated with FOLFIRI + escalating dose of cetuximab (arm A). It is expected that the PFS rate will be similar to that observed after standard cetuximab treatment + FOLFIRI in patients with grade 1-4 skin toxicity in a K-Ras wild type population (CRYSTAL study).;Secondary Objective: To evaluate PFS, overall survival (OS), overall response and response rate in liver-limited disease, disease control rate, duration of response, general resection rate and R0 resection rate for metastatic lesions, skin toxicity, general safety, biomarkers, proteomics, expression profiling, mutations in each of the treatment arms.<br><br>To evaluate pharmacokinetic parameters in patients in both treatment arms in selected centers.<br>;Primary end point(s): Progression Free Survival rate at 9 months in the dose escalation arm.