A randomized phase II trial assessing Sorafenib (Nexavar®) in combination with irinotecan in metastatic colorectal cancer patients with KRAS mutated tumours after failure of all active drugs known to be effective. - NEXIRI 2

Phase 1

• Conditions: metastatic colorectal cancer; MedDRA version: 16.0Level: LLTClassification code 10052362Term: Metastatic colorectal cancerSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2012-000644-94-FR
• Lead Sponsor: Centre Val d’Aurelle - Paul Lamarque

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2012-09-03
• Last Update Posted: 8 March 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 159

Inclusion Criteria

-Male or female = 18 years old
-Histologically confirmed diagnosis of colorectal cancer
-Asymptomatic or resected primary tumor
-Metastatic colorectal cancer not eligible for curative surgery
-At least one target lesion:
- Unidimensionally measurable on cross-sectional imaging
- In an area not previously irradiated
-Disease progression after failure of active drugs (5-Fu or 5-Fu prodrugs, irinotecan, oxaliplatin, bevacizumab)
-WHO performance status = 2
-Confirmation of KRAS mutation in codons 12 or 13 in the primary tumor or metastases
-Total bilirubin = 1.5 ULN, ALT or AST = 2.5 ULN (or < 5 in case of liver impairment)
-Haemoglobin = 10 g/dL, neutrophils = 1,500/mm3, platelets = 100,000/mm3
-Amylase and lipase < 1.5 ULN
-Serum creatinine = 1.5 ULN
-Negative pregnancy test in women of childbearing potential
-Use of an effective contraceptive method during the whole treatment and up to 3 months after the completion of treatment
-Life expectancy > 3 months
-Informed consent signed prior any study specific procedures.
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

-History of Gilbert’s syndrome
-Symptomatic brain metastases or carcinomatous meningitis
-Bone-only metastases
-History or presence of other cancer within the past 5 years (except curatively treated nonmelanoma skin cancer)
-Prior surgery or radiotherapy within 4 weeks before entering the study
-Cardiac arrhythmia requiring treatment (except for beta-blockers and digoxin), unstable cardiac disease, myocardial infarction within the previous 6 months, > grade II NYHA heart failure, uncontrolled hypertension
-History of epileptic seizures requiring long-term anticonvulsant therapy
-History of organ transplantation with use of immunosuppression therapy
-Severe bacterial or fungal infection (Grade > 2 NCI-CTCAE v.3.0)
-HIV infection
-Long-term use of CYP 3A4 enzyme-inducing agents such as rifampicin, St. John's Wort (hypericum perforatum), phenytoin, carbamazepine, phenobarbital, dexamethasone, and ketoconazole
-Pregnant or breastfeeding women
-Bowel malabsorption or extended bowel resection that could affect the absorption of sorafenib, occlusive syndrom, inability to take oral medications
-Inflammatory bowel disease with chronic diarrhea (NCI N+Bethesda = 1.2g)
-Participation in another clinical trial 30 days prior to study entry
-Concurrent treatment with any other investigational product or anticancer therapy (except for irinotecan or sorafenib)
-Psychological, social, geographical disorders or any other condition that would preclude study compliance (treatment administration and study follow-up).

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the median progression free survival defined as the time from randomization to disease progression according to RECIST criteria (Version 1.1) or death from any cause<br><br><br>;Secondary Objective: - Disease control rate and response rate<br>- Treatment-related toxicity (NCI CTC V4.0)<br>- Overall survival<br>- Quality of life;Primary end point(s): The primary assessment criterion is the median progression free survival (PFS), evaluated according to the RECIST criteria (v1.1) by chest-abdomen-pelvis CT-scan every 8 weeks. A complete or partial response will have to be confirmed 4 weeks after the initial observation. All responses will be reviewed by a panel of independent radiologists.