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

Sponsor

Centre Hospitalier Universitaire de Besancon (Other)

Overall Status

Recruiting

CT.gov ID

NCT03117972

Collaborator

(none)

177

Enrollment

Locations

Arms

73.9

Anticipated Duration (Months)

14.8

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Colorectal Cancer	Drug: FOLFOXIRI Drug: FOLFOX Drug: FOLFIRI Drug: Bevacizumab Drug: LV5FU2 Drug: Capecitabine	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

177 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Aug 4, 2017

Anticipated Primary Completion Date :

Apr 1, 2023

Anticipated Study Completion Date :

Oct 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A : FOLFOXIRI - bevacizumab FOLFOXIRI + bevacizumab, 12 cures following by maintenance chemotherapy (bevacizumab + LV5FU2 or bevacizumab-capecitabine) until disease progression or limiting toxicities	Drug: FOLFOXIRI 12 cycles Other Names: Irinotecan Oxaliplatin Leucovorin 5-Fluorouracil Drug: Bevacizumab 12 cycles Drug: LV5FU2 Maintenance chemotherapy Drug: Capecitabine Maintenance chemotherapy
Active Comparator: Arm B: FOLFOX or FOLFIRI - bevacizumab FOLFOX or FOLFIRI + bevacizumab 12 cures following by maintenance chemotherapy (bevacizumab + LV5FU2 ou bevacizumab capecitabine) until disease progression or limiting toxicities	Drug: FOLFOX 12 cycles Other Names: Oxaliplatin 5-Fluorouracil Drug: FOLFIRI 12 cycles Other Names: Ironotecan Leucovorin 5-Fluorouracil Drug: Bevacizumab 12 cycles Drug: LV5FU2 Maintenance chemotherapy Drug: Capecitabine Maintenance chemotherapy

Arm

Intervention/Treatment

Experimental: Arm A : FOLFOXIRI - bevacizumab

FOLFOXIRI + bevacizumab, 12 cures following by maintenance chemotherapy (bevacizumab + LV5FU2 or bevacizumab-capecitabine) until disease progression or limiting toxicities

Drug: FOLFOXIRI

12 cycles

Other Names:

Irinotecan

Oxaliplatin

Leucovorin

5-Fluorouracil

Drug: Bevacizumab

12 cycles

Drug: LV5FU2

Maintenance chemotherapy

Drug: Capecitabine

Maintenance chemotherapy

Active Comparator: Arm B: FOLFOX or FOLFIRI - bevacizumab

FOLFOX or FOLFIRI + bevacizumab 12 cures following by maintenance chemotherapy (bevacizumab + LV5FU2 ou bevacizumab capecitabine) until disease progression or limiting toxicities

Drug: FOLFOX

12 cycles

Other Names:

Oxaliplatin

5-Fluorouracil

Drug: FOLFIRI

12 cycles

Other Names:

Ironotecan

Leucovorin

5-Fluorouracil

Drug: Bevacizumab

12 cycles

Drug: LV5FU2

Maintenance chemotherapy

Drug: Capecitabine

Maintenance chemotherapy

Outcome Measures

Primary Outcome Measures

Progression Free Survival [up to 4 years (3 years of inclusion and 12 months of follow up after the last patient included)]
Delay from the date of randomization to the disease progression (RECIST) or death from any cause whichever occurs first

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 76 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Centre Hospitalier Universitaire de Besançon	Besançon	France	25000
2	Centre Hospitalier de Boulogne sur Mer	Boulogne-sur-Mer	France
3	CH de Colmar	Colmar	France
4	Institut de Cancérologie de Bourgogne	Dijon	France	21000
5	CHRU de LILLE	Lille	France	59037
6	Hôpital Nord Franche-Comté	Montbéliard	France	25209
7	Institut de Cancérolgie de Montpellier- ICM	Montpellier	France	34070
8	CHU de REIMS, Hôpital Robert Debré	Reims	France
9	Clinique Sainte Anne	Strasbourg	France	67000
10	Centre Paul Strauss	Strasbourg	France	67065
11	CHU de Tours	Tours	France	37044
12	CHI de Haute-Saône	Vesoul	France	70014