Clinical trial NCT01677884: Intra-arterial Hepatic Bevacizumab and Systemic Chemotherapy
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colorectal Neoplasms
Lead sponsor: Gustave Roussy, Cancer Campus, Grand Paris
Sponsor class: OTHER
First posted: 2012-09-03
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility criteria: 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.

Primary outcomes:
measure: Efficiency of treatment based on objective response rate
timeFrame: Every 9 weeks from the start to tumoral progression
Secondary outcomes:
measure: Treatment toxicity based on NCI-CTC v4.0
timeFrame: Every 3 weeks from the start to tumoral progression or toxicity preventing further processing
measure: Progression Free Survival
timeFrame: Every 9 weeks form the start to tumoral progression
measure: Hepatic metastasis resection rate
timeFrame: Assessed up 6 months after the end of treatment
Other outcomes:
measure: Total area under the curve of contrast-enhanced liver ultrasound
timeFrame: Assessed up in baseline, D7, D14, W4, W7 and every 9 weeks up to progression
Locations:
city: Villejuif
country: France
facility: Institut Gustave Roussy
state: Val de Marne
Study officials:
affiliation: Gustave Roussy, Cancer Campus, Grand Paris
name: Michel Ducreux, MD-PhD
role: PRINCIPAL_INVESTIGATOR
References: