Bevacizumab-based Chemotherapy Adapted to Bevacizumab Pharmacokinetics in 1st-line Treatment

NCT ID: NCT06642844

Last Updated: 2024-10-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

244 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-10-30

Study Completion Date

2029-10-30

Brief Summary

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Bevacizumab is a standard drug for metastatic colorectal cancer (mCRC) in combination with cytotoxic chemotherapy. However, inter-individual pharmacokinetic variability was observed for bevacizumab and an exposure-response relationship for efficacy was described for bevacizumab in mCRC patients treated with 1st-line bevacizumab-based chemotherapy.

Detailed Description

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The primary objective is to evaluate the effect of doubling the dose of bevacizumab in mCRC patients whose initial serum bevacizumab concentration is ≤15.5 mg/L on progression-free survival (PFS).

This project is a multicenter, double-blind, randomized trial in two parallel groups.

The primary endpoint is progression-free survival (PFS)

Conditions

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Unresectable Metastatic Colorectal Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

This project is a multicenter, double-blind, randomized trial in two parallel groups.
Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators
Double blinding (patients and investigators) will be applied to this trial with respect to the dose of bevacizumab administered throughout the study, except in specific circumstances such as in emergency cases, and only if knowledge of the dose is likely to influence management.

The dose of bevacizumab will be administered in 2 preparations and in the following order:

* 1\. Preparation at 5 mg/kg, open label;
* 2\. Preparation at 5 mg/kg or placebo, blinded.

Study Groups

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Experimental: Group A

Patients randomized to the experimental group of the trial will receive bevacizumab as an IV infusion at a dose of 10 mg/kg, administered in 2 preparations of 5 mg/kg, every 2 weeks. Patients will receive treatment until progression, patient refusal, or unacceptable toxicity.

Group Type EXPERIMENTAL

Avastin, 25 Mg/mL Intravenous Solution

Intervention Type DRUG

Experimental group/ Patients randomized to the experimental group of the trial will receive bevacizumab as an IV infusion at a dose of 10 mg/kg, administered in 2 preparations of 5 mg/kg, every 2 weeks. Patients will receive treatment until progression, patient refusal, or unacceptable toxicity.

Control group: Patients randomized to the control group of the trial will receive bevacizumab at a dose of 5 mg/kg and placebo (NaCl) every two weeks. Patients will receive treatment until progression, patient refusal, or unacceptable toxicity.

Active comparator: Group B

Patients randomized to the control group of the trial will receive bevacizumab at a dose of 5 mg/kg and placebo (NaCl) every two weeks. Patients will receive treatment until progression, patient refusal, or unacceptable toxicity.

Group Type ACTIVE_COMPARATOR

Avastin, 25 Mg/mL Intravenous Solution

Intervention Type DRUG

Experimental group/ Patients randomized to the experimental group of the trial will receive bevacizumab as an IV infusion at a dose of 10 mg/kg, administered in 2 preparations of 5 mg/kg, every 2 weeks. Patients will receive treatment until progression, patient refusal, or unacceptable toxicity.

Control group: Patients randomized to the control group of the trial will receive bevacizumab at a dose of 5 mg/kg and placebo (NaCl) every two weeks. Patients will receive treatment until progression, patient refusal, or unacceptable toxicity.

Interventions

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Avastin, 25 Mg/mL Intravenous Solution

Experimental group/ Patients randomized to the experimental group of the trial will receive bevacizumab as an IV infusion at a dose of 10 mg/kg, administered in 2 preparations of 5 mg/kg, every 2 weeks. Patients will receive treatment until progression, patient refusal, or unacceptable toxicity.

Control group: Patients randomized to the control group of the trial will receive bevacizumab at a dose of 5 mg/kg and placebo (NaCl) every two weeks. Patients will receive treatment until progression, patient refusal, or unacceptable toxicity.

Intervention Type DRUG

Other Intervention Names

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Experimental group Control group

Eligibility Criteria

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Inclusion Criteria

* Patients aged ≥18 years.
* Histologically proven metastatic colorectal adenocarcinoma (on primary tumor and/or metastases) inoperable, well documented, i.e. not compatible with complete oncological resection at inclusion.
* For whom treatment with bevacizumab is indicated.
* For women of childbearing age: effective contraception.
* ECOG Performance status (PS) 0-2.
* No prior treatment of metastatic disease (in the case of adjuvant treatment, interval between the end of chemotherapy and relapse \> 6 months if fluoropyrimidine alone or \> 12 months if FOLFOX).
* At least one evaluable or measurable lesion assessed by computed tomography (CT) according to RECIST v1.1 criteria.
* Life expectancy greater than 3 months.
* Adequate hematological, renal and hepatic biological parameters: neutrophils ≥ 1.5x109/L; platelets ≥ 100x109/L; hemoglobin ≥ 9 g/dL; serum creatinine \<150 μmol/L; bilirubinemia ≤ 1.5 x upper limit of normal (ULN), alkaline phosphatase \< 5xULN; proteinuria \< 2+ (urine dipstick) or ≤ 1 g/24h.
* Written informed consent signed by the patient.
* Patient affiliated to a French social security system.

Randomization criteria in the experimental phase:

\- Serum concentration of bevacizumab on D14 ≤ 15.5 mg/L (measured just before the 2nd infusion of bevacizumab).

Exclusion Criteria

Less than 6 months from the end of any prior chemotherapy, radiotherapy or adjuvant surgery.

* Patient with a known non-indication or contraindication to first-line chemotherapy based on bevacizumab.
* Cardiovascular contraindication to the prescription of bevacizumab: heart failure, cardiovascular event within 6 months, NYHA ≥ 2 (New York Heart Association), poorly controlled arterial hypertension, history of hypertensive crisis or hypertensive encephalopathy; Grade 3/4 anterior venous thromboembolism (NCI-CTCAE)
* Inadequate hematological, hepatic and renal function
* Urine test strip for proteinuria ≥ 2+ unless proteinuria \< 1 g / 24 hours is demonstrated.
* Current or recent (within 10 days of study enrollment) use of aspirin (\>325 mg/day) or clopidogrel (\>75 mg/day).
* Current or recent use (within 10 days before the first dose of bevacizumab) of oral or parenteral therapeutic anticoagulants or thrombolytic agents for therapeutic purposes.
* Untreated CNS metastases or treatment of brain metastases, either by surgical or radiological techniques, must have been completed more than 4 weeks before the first study treatment.
* Surgical procedure (including open biopsy, surgical resection, wound revision, or other major surgery involving entry into a body cavity) or significant traumatic injury within 28 days prior to study enrollment or anticipation of study need for major surgery during the study.
* Serious non-healing wound, active ulcer or untreated bone fracture.
* Other neoplasias (previous or current), except:

* i/ carcinoma in situ of the cervix adequately treated,
* ii/ basal cell or squamous cell carcinoma of the skin,
* iii/ cancer in complete remission for more than 5 years.
* Other illnesses, which, according to the doctor, are life-threatening to the patient and/or which are uncontrolled.
* Primary tumor in place and symptomatic (occlusion, hemorrhage).
* Pregnant or breastfeeding women.
* Patients unable to give consent.
* Patients under guardianship, curatorship or legal protection.
Minimum Eligible Age

18 Years

Maximum Eligible Age

99 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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CHU DE BESANCON

UNKNOWN

Sponsor Role collaborator

Gustave Roussy, Cancer Campus, Grand Paris

OTHER

Sponsor Role collaborator

CHU de Clermont-Ferrand

UNKNOWN

Sponsor Role collaborator

CHU de Reims

OTHER

Sponsor Role collaborator

CHU de Brest

UNKNOWN

Sponsor Role collaborator

AP-HP, Hôpital Pitié- Salpétrière

UNKNOWN

Sponsor Role collaborator

University Hospital, Rouen

OTHER

Sponsor Role collaborator

Poitiers University Hospital

OTHER

Sponsor Role collaborator

Institut Paoli-Calmettes

OTHER

Sponsor Role collaborator

Rennes University Hospital

OTHER

Sponsor Role collaborator

University Hospital, Toulouse

OTHER

Sponsor Role collaborator

AP-HP, Hôpital Saint-Louis

UNKNOWN

Sponsor Role collaborator

HCL Hôpital Edouard Hériot

UNKNOWN

Sponsor Role collaborator

Centre Hospitalier Universitaire Dijon

OTHER

Sponsor Role collaborator

Nantes University Hospital

OTHER

Sponsor Role collaborator

Centre Hospitalier Universitaire, Amiens

OTHER

Sponsor Role collaborator

Hôpital Privé Jean Mermoz

UNKNOWN

Sponsor Role collaborator

AP-HP, Hôpital Henri Mondor

UNKNOWN

Sponsor Role collaborator

AP-HP, Hôpital Paul Brousse

UNKNOWN

Sponsor Role collaborator

CHG de St-Malo

UNKNOWN

Sponsor Role collaborator

Polyclinique de Blois

UNKNOWN

Sponsor Role collaborator

University Hospital, Caen

OTHER

Sponsor Role collaborator

Central Hospital, Nancy, France

OTHER

Sponsor Role collaborator

University Hospital, Tours

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Christophe Borg

Role: PRINCIPAL_INVESTIGATOR

Besançon, FRANCE

Michel Ducreux

Role: PRINCIPAL_INVESTIGATOR

Gustave Roussy, FRANCE

Caroline Petorin

Role: PRINCIPAL_INVESTIGATOR

Clermont-Ferrand, FRANCE

Olivier Bouché

Role: PRINCIPAL_INVESTIGATOR

Reims, FRANCE

Jean-Philippe Metges

Role: PRINCIPAL_INVESTIGATOR

Brest, FRANCE

Jean-Baptiste Bachet

Role: PRINCIPAL_INVESTIGATOR

Pitié- Salpétrière, FRANCE

Frédéric Di Fiore

Role: PRINCIPAL_INVESTIGATOR

Rouen, FRANCE

David Tougeron

Role: PRINCIPAL_INVESTIGATOR

Poitiers, FRANCE

Astrid Lièvre

Role: PRINCIPAL_INVESTIGATOR

Rennes, FRANCE

Rosine Guimbaud

Role: PRINCIPAL_INVESTIGATOR

Toulouse , FRANCE

Thomas Aparicio

Role: PRINCIPAL_INVESTIGATOR

St Louis , FRANCE

Thomas Walter

Role: PRINCIPAL_INVESTIGATOR

Edouard Hériot, FRANCE

Côme Lepage

Role: PRINCIPAL_INVESTIGATOR

Dijon, FRANCE

Yann Touchefeu

Role: PRINCIPAL_INVESTIGATOR

Nantes, FRANCE

Vincent Hautefeuille

Role: PRINCIPAL_INVESTIGATOR

Amiens, FRANCE

Pascal Artru

Role: PRINCIPAL_INVESTIGATOR

Jean Mermoz, FRANCE

Christophe Tournigand

Role: PRINCIPAL_INVESTIGATOR

Henri Mondor, France

Pascal Hammel

Role: PRINCIPAL_INVESTIGATOR

Paul Brousse, FRANCE

Romain Desgrippes

Role: PRINCIPAL_INVESTIGATOR

St-Malo, FRANCE

Philippe Laplaige

Role: PRINCIPAL_INVESTIGATOR

Blois, FRANCE

Karine Bouhier-Leporrier

Role: PRINCIPAL_INVESTIGATOR

Caen, FRANCE

Marie Muller

Role: PRINCIPAL_INVESTIGATOR

Nancy, france

Central Contacts

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Thierry Lecomte

Role: CONTACT

0247475900

Adeline MOUSSET

Role: CONTACT

0218370645

Other Identifiers

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DR230009

Identifier Type: -

Identifier Source: org_study_id

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