Sorafenib in Combination With Irinotecan in Metastatic Colorectal Cancer Patients With KRAS Mutated Tumors

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT01715441
• Date of registration: 19/10/2012
• Prospective Registration: No
• Primary sponsor: Institut du Cancer de Montpellier - Val d'Aurelle
• Public title: Sorafenib in Combination With Irinotecan in Metastatic Colorectal Cancer Patients With KRAS Mutated Tumors NEXIRI2
• Scientific title: A Randomized Phase II Trial Assessing Sorafenib in Combination With Irinotecan in Metastatic Colorectal Cancer Patients With KRAS Mutated Tumors After Failure of All Drugs Known to be Effective
• Date of first enrolment: September 2012
• Target sample size: 173
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01715441
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Crossover Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

France

Contacts

• Name: Emmanuelle SAMALIN, MD
• Affiliation: CRLC Val d'Aurelle-Paul Lamarque

• Name: Marc YCHOU, MD,
• Affiliation: CRLC Val d'Aurelle

Key inclusion & exclusion criteria

Inclusion Criteria:

- Male or female = 18 years old

- Histologically confirmed diagnosis of colorectal cancer

- Asymptomatic or resected primary tumor

- Metastatic colorectal cancer patient 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)

- Patients with bone metastases are eligible if they have other measurable lesions

- 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

- 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 in males and females

- Life expectancy of at least 3 months

- Informed consent signed prior any study specific procedures

- Tumor evaluation should be performed within 3 weeks prior to starting treatment

Exclusion Criteria:

- History of Gilbert's syndrome

- Symptomatic brain metastases or carcinomatous meningitis

- Bone-only metastases

- History or presence of other cancers within the past 5 years (except curatively
treated non-melanoma skin cancer and in situ cervical 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

- Kalemia lower than normal serum potassium value

- From ECG, QTc interval > 470 ms

- History of acute or chronic pancreatitis

- 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.4.0)

- Known 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 syndrome, inability to take oral medications

- Inflammatory bowel disease with chronic diarrhea (NCI-CTCAE v.4.0)

- 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).



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Metastatic Colorectal Cancer Patients With KRAS Mutated Tumors

Intervention(s)

Drug: Irinotecan monotherapy

Drug: Sorafenib and irinotecan combination

Drug: Sorafenib monotherapy

Primary Outcome(s)

Non-progression rate [Time Frame: At 2 months]

Secondary Outcome(s)

Disease control rate [Time Frame: At 2 months]

Overall survival [Time Frame: At 6 months]

Progression Free Survival [Time Frame: At 6 months]

Response rate [Time Frame: At 2 months]

Treatment-related toxicity [Time Frame: At 6 months]

Quality of life questionnaire [Time Frame: 6 months]

Secondary ID(s)

2012-000644-94

NEXIRI2

Source(s) of Monetary Support

Please refer to primary and secondary sponsors