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

NCT03117972 | Terminated Phase 2

• 1 other identifier: API/2016/73
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 10

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.

Conditions

Metastatic Colorectal Cancer

Keywords

Metastatic colorectal cancer; Biomarker; Chemotherapy intensification; Syndecan1; LDH; CD138

Outcome Measures

Primary Outcomes (1)

• 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)

Study Arms (2)

Arm A : FOLFOXIRI - bevacizumab

EXPERIMENTAL

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

Drug: FOLFOXIRI; Drug: Bevacizumab; Drug: LV5FU2; Drug: Capecitabine

Arm B: FOLFOX or FOLFIRI - bevacizumab

ACTIVE COMPARATOR

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

Drug: FOLFOX; Drug: FOLFIRI; Drug: Bevacizumab; Drug: LV5FU2; Drug: Capecitabine

Interventions

FOLFOXIRI DRUG

12 cycles

Also known as: Irinotecan, Oxaliplatin, Leucovorin, 5-Fluorouracil

Arm A : FOLFOXIRI - bevacizumab

FOLFOX DRUG

12 cycles

Also known as: Oxaliplatin, 5-Fluorouracil

Arm B: FOLFOX or FOLFIRI - bevacizumab

FOLFIRI DRUG

12 cycles

Also known as: Ironotecan, Leucovorin, 5-Fluorouracil

Arm B: FOLFOX or FOLFIRI - bevacizumab

Bevacizumab DRUG

12 cycles

Arm A : FOLFOXIRI - bevacizumab; Arm B: FOLFOX or FOLFIRI - bevacizumab

LV5FU2 DRUG

Maintenance chemotherapy

Arm A : FOLFOXIRI - bevacizumab; Arm B: FOLFOX or FOLFIRI - bevacizumab

Capecitabine DRUG

Maintenance chemotherapy

Arm A : FOLFOXIRI - bevacizumab; Arm B: FOLFOX or FOLFIRI - bevacizumab

Eligibility Criteria

• Age: 18 Years - 76 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Besancon: lead

Study Sites (10)

Centre Hospitalier Universitaire de Besançon

Besançon, 25000, France

Location

Centre Hospitalier de Boulogne sur Mer

Boulogne-sur-Mer, France

Location

CH de Colmar

Colmar, France

Location

Institut de Cancérologie de Bourgogne

Dijon, 21000, France

Location

CHRU de LILLE

Lille, 59037, France

Location

Hôpital Nord Franche-Comté

Montbéliard, 25209, France

Location

CHU de REIMS, Hôpital Robert Debré

Reims, France

Location

Clinique Sainte Anne

Strasbourg, 67000, France

Location

Centre Paul Strauss

Strasbourg, 67065, France

Location

CHU de Tours

Tours, 37044, France

Location

Related Publications (1)

• Jary M, Lecomte T, Bouche O, Kim S, Dobi E, Queiroz L, Ghiringhelli F, Etienne H, Leger J, Godet Y, Balland J, Lakkis Z, Adotevi O, Bonnetain F, Borg C, Vernerey D. Prognostic value of baseline seric Syndecan-1 in initially unresectable metastatic colorectal cancer patients: a simple biological score. Int J Cancer. 2016 Nov 15;139(10):2325-35. doi: 10.1002/ijc.30367. Epub 2016 Aug 13.

  PMID: 27472156 BACKGROUND

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

FOLFOXIRI protocol; Irinotecan; Oxaliplatin; Leucovorin; Fluorouracil; Folfox protocol; IFL protocol; Bevacizumab; Capecitabine

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds; Coordination Complexes; Organic Chemicals; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Christophe BORG, Pr

  Centre Hospitalier Universitaire de Besançon

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 13, 2017
• First Posted: April 18, 2017
• Study Start: August 4, 2017
• Primary Completion: August 7, 2024
• Study Completion: November 18, 2024
• Last Updated: February 5, 2025

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

FR (10)