Intra-arterial Hepatic Bevacizumab and Systemic Chemotherapy

Study Overview
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Brief Summary
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The purpose of the study is to assessed the efficiency of treatment based on the objective response rate (RECIST 1.1)

Official Title
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Intra-arterial Hepatic Bevacizumab and Systemic Chemotherapy in Hepatic Metastases of Metastatic Colorectal Cancer: a Phase II Multicentric Study With Patients in Progression After First Line Systemic Chemotherapy

Conditions
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Colorectal Neoplasms

Intervention / Treatment
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* Drug: Bevacizumab
* Drug: Capecitabine
* Drug: Irinotecan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Liver metastases of colon cancer or rectal predominant (histological evidence obtained on the primary tumor or liver metastases) Isolated (no extra-hepatic metastasis, primary tumor resected) No access to curative hepatectomy (R0 resection foreseeable or not leaving less than 30% residual non-tumor liver normally vascularized), or requiring complex hepatectomy, very large (5 or more segments) and / or risked (class II CPP) which at least one measurable by RECIST (>2 cm, or >1 cm if Computed tomography (CT) spiraled) Or extra-hepatic disease of small size potentially accessible to a resection (one or two lung metastases, lymphadenopathy localized accessible to curative resection) colon or rectal primary tumor : resected or asymptomatic Progression after first line chemotherapy to treat the metastatic disease, all types of treatment allowed except intra-arterial Bevacizumab Age >18 years <75 years Performance status WHO 0 or 1 Life expectancy >3 months Bilirubin <1.5 times the upper limit of normal (N), ASAT and ALAT <5N, creatinine <1.5 N neutrophils >1.5 x 10^9/L, platelets ≥100 x 10^9/L, hemoglobin >9g/dL. Patients may be included even if they were transfused CT (or MRI) reference for the measurement of metastases performed within 28 days before the first treatment cycle Information of the patient or legal representative signing the informed consent Affiliated to a social security system Exclusion Criteria: Symptomatic colon or rectal primary tumor (sub-occlusion, significant hemorrhage, major rectal syndrome) Extra-hepatic metastases other than small size disease potentially accessible after resection Grade 3-4 allergy to one of the treatment compounds Two lines of prior chemotherapy. One line is allowed for metastatic disease but must have been started more than 6 months after completion of adjuvant treatment. Participation during or within 30 days before study to another therapeutic trial with an experimental molecule Concomitant cancer systemic treatment using immunotherapy, chemotherapy or hormone Symptomatic CHD or myocardial infarction within 6 months prior entry into the study, cardiac arrhythmia uncontrolled despite treatment Uncontrolled hypertension (blood pressure >150/100 mm Hg despite hypertensive treatment) Heart Failure >Grade II of the New York Heart Association (NYHA) (class II-III-IV)severe renal failure History and / or presence of bleeding disorders and/or thrombotic <6 months Uncontrolled Serious illness, uncontrolled active infection or other serious underlying condition which may prevent the patient to receive treatment Pregnancy (or positive pregnancy test at baseline), lactation or no contraception effective for men or women of childbearing age Occlusion or sub-bowel obstruction or history of inflammatory bowel disease Other cancer within 5 years prior to entry into the trial or concomitant (except in situ cancer of the cervix or skin basal-cell carcinoma properly treated) Legal inability (persons deprived of liberty or under guardianship) Inability to sign the consent or submit to medical test for geographical, social or psychological reasons.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Patients with metastatic CRC<br> | Drug: Bevacizumab<br>* Every 3 weeks : 7.5 mg/kg intra arterial in 2 hours at D1<br>Drug: Capecitabine<br>* Every 3 weeks: 2000 mg/m²/d in 2 times/d from D1 to D4<br>Drug: Irinotecan<br>* Every 3 weeks: 200mg/m² in 30mn IV at D1 (if oxaliplatin in first line) or oxaliplatin 130mg/m² in 2h IV at D1 (if irinotecan in first line)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficiency of treatment based on objective response rate |  | Every 9 weeks from the start to tumoral progression | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment toxicity based on NCI-CTC v4.0 |  | Every 3 weeks from the start to tumoral progression or toxicity preventing further processing | 
| Progression Free Survival |  | Every 9 weeks form the start to tumoral progression | 
| Hepatic metastasis resection rate |  | Assessed up 6 months after the end of treatment |