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
Overview
- Phase
- Phase 2
- Intervention
- Irinotecan monotherapy
- Conditions
- Metastatic Colorectal Cancer Patients With KRAS Mutated Tumors
- Sponsor
- Institut du Cancer de Montpellier - Val d'Aurelle
- Enrollment
- 173
- Locations
- 9
- Primary Endpoint
- Non-progression rate
- Status
- Completed
- Last Updated
- 2 months ago
Overview
Brief Summary
The aim of this multicenter randomized phase II trial is to determine the efficacy of sorafenib and irinotecan combination versus irinotecan monotherapy or versus sorafenib monotherapy in metastatic colorectal cancer patients with KRAS mutated tumors after failure of all active drugs known to be effective.
Investigators
Eligibility 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
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
Arms & Interventions
Irinotecan monotherapy
Intravenous infusion irinotecan 180 mg/m2 over 90 minutes (D1=D15) with cross over to irinotecan and sorafenib combination at progression.
Intervention: Irinotecan monotherapy
Sorafenib monotherapy
Oral sorafenib 400 mg twice daily (total dose 800 mg/day) with cross over to irinotecan and sorafenib combination at progression
Intervention: Sorafenib monotherapy
Sorafenib and irinotecan combination
Intravenous infusion irinotecan 120 mg/m2 over 90 minutes (D1=D15) at Cycle 1, 150 mg/m² at C2 if no diarrhea \> grade 1 and no other toxicity \> grade 2, and 180 mg/m² at C3 in the same conditions * Oral sorafenib 400 mg twice daily (total dose 800 mg/day) from C1. 1 cycle = 15 days and 1 course = 4 weeks.
Intervention: Sorafenib and irinotecan combination
Outcomes
Primary Outcomes
Non-progression rate
Time Frame: At 2 months
To evaluate the non-progression rate at 2 months according to RECIST criteria (Version 1.1)
Secondary Outcomes
- Disease control rate(At 2 months)
- Treatment-related toxicity(At 6 months)
- Overall survival(At 6 months)
- Quality of life questionnaire(6 months)
- Progression Free Survival(At 6 months)
- Response rate(At 2 months)