Intra-arterial Hepatic Bevacizumab and Systemic Chemotherapy (BEVIAC)

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

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

Study Overview

• Status: Completed
• Conditions: Colorectal Neoplasms
• Intervention / Treatment: Drug: Bevacizumab; Drug: Capecitabine; Drug: Irinotecan

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Val de Marne
    • Villejuif, Val de Marne, France, 94805
      • Institut Gustave Roussy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patients with metastatic CRC	Drug: Bevacizumab; Every 3 weeks : 7.5 mg/kg intra arterial in 2 hours at D1; Drug: Capecitabine; Every 3 weeks: 2000 mg/m²/d in 2 times/d from D1 to D4; Drug: Irinotecan; 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)

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Other Outcome Measures

Outcome Measure	Time Frame
Total area under the curve of contrast-enhanced liver ultrasound	Assessed up in baseline, D7, D14, W4, W7 and every 9 weeks up to progression

Collaborators and Investigators

• Sponsor: Gustave Roussy, Cancer Campus, Grand Paris
• Investigators: Principal Investigator: Michel Ducreux, MD-PhD, Gustave Roussy, Cancer Campus, Grand Paris

Study record dates

Study Major Dates

• Study Start: November 1, 2012
• Primary Completion (Actual): February 1, 2016
• Study Completion (Actual): February 1, 2016

Study Registration Dates

• First Submitted: August 30, 2012
• First Submitted That Met QC Criteria: August 30, 2012
• First Posted (Estimate): September 3, 2012

Study Record Updates

• Last Update Posted (Estimate): June 9, 2016
• Last Update Submitted That Met QC Criteria: June 8, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Topoisomerase I Inhibitors; Capecitabine; Bevacizumab; Irinotecan
• Other Study ID Numbers: 2011-005559-15; CSET 2011/1827 (Other Identifier: Institut Gustave Roussy)