Chemotherapy Intensification in Patients With High Lactate Dehydrogenase Values and Soluble Syndecan1 Levels

Study Overview
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Brief Summary
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In first-line metastatic colorectal cancer (mCRC), baseline prognostic factors allowing death risk and strategy stratification are lacking. In this setting, a simple biological scoring system have recently been proposed, including LDH and CD138 binary status seric values, identifying one third of patients with worst prognostic. Intensified-chemotherapy strategies, combining 5-fluorouracile, Oxaliplatin, Irinotecan and Bevacizumab, are beneficial for patients having a bad prognostic, defined by the BRAFV600E mutation, concerning 5-8% of first line mCRC. For the 30% of patients with LDH-CD138 elevated score, the purpose of CLavSyn phase II study is to compare the PFS of one intensified arm (FOLFOXIRI Bevacizumab) to one standard chemotherapy arm, in order to better discriminate treatment strategies, at metastatic diagnosis.

Official Title
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Chemotherapy Intensification in Patients With High Lactate Dehydrogenase Values and Soluble Syndecan-1 Levels

Conditions
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Metastatic Colorectal Cancer

Intervention / Treatment
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* Drug: FOLFOXIRI
* Drug: FOLFOX
* Drug: FOLFIRI
* Drug: Bevacizumab
* Drug: LV5FU2
* Drug: Capecitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Performance status ECOG-WHO 0 or 1 Histologically proved metastatic colorectal adenocarcinoma, with non-resectable metastases Adequate hematological, hepatic, and renal functions Signed written informed consent Exclusion Criteria: Previous treatment (chemotherapy, targeted therapy, surgery) for metastatic disease History of autoimmune disease Acute infectious disease Known hypersensitivity grade 3-4 or contraindication to any of the study drugs Patient with any medical or psychiatric condition or disease which would make the patient inappropriate for entry into this study. Bevacizumab contraindication Brain metastases Other malignancy within the last 2 years, except for adequately treated carcinoma in situ of the cervix or squamous carcinoma of the skin, or adequately controlled limited basal cell skin cancer. Pregnancy, breast-feeding or absence of adequate contraception for fertile patients Patient under guardianship, curator or under the protection of justice.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 76 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A : FOLFOXIRI - bevacizumab<br>FOLFOXIRI + bevacizumab, 12 cures following by maintenance chemotherapy (bevacizumab + LV5FU2 or bevacizumab-capecitabine) until disease progression or limiting toxicities | Drug: FOLFOXIRI<br>* 12 cycles<br>* Other names: 5-Fluorouracil;Drug: Bevacizumab<br>* 12 cycles<br>Drug: LV5FU2<br>* Maintenance chemotherapy<br>Drug: Capecitabine<br>* Maintenance chemotherapy<br>|
| Active Comparator: Arm B: FOLFOX or FOLFIRI - bevacizumab<br>FOLFOX or FOLFIRI + bevacizumab 12 cures following by maintenance chemotherapy (bevacizumab + LV5FU2 ou bevacizumab capecitabine) until disease progression or limiting toxicities | Drug: FOLFOX<br>* 12 cycles<br>* Other names: 5-Fluorouracil;Drug: FOLFIRI<br>* 12 cycles<br>* Other names: 5-Fluorouracil;Drug: Bevacizumab<br>* 12 cycles<br>Drug: LV5FU2<br>* Maintenance chemotherapy<br>Drug: Capecitabine<br>* Maintenance chemotherapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival | Delay from the date of randomization to the disease progression (RECIST) or death from any cause whichever occurs first | up to 4 years (3 years of inclusion and 12 months of follow up after the last patient included) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metastatic colorectal cancer, Biomarker, Chemotherapy intensification, Syndecan1, LDH, CD138