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

NCT06642844 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: DR230009
• Study Type: interventional
• Target: 244
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Unresectable Metastatic Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• The primary endpoint is progression-free survival (PFS)

  The SS was defined as the time interval for randomized patients between the date of start of treatment and date of first clinical and/or radiological progression or death whatever the cause, in depending on what survives first.of first clinical and/or radiological progression or death whatever the cause, in depending on what survives first.progression (PD) per RECIST 1.1 or death due to any cause, whichever occurs first. A patient alive without progression will be censored on the date from the last follow-up visit.

  up to death

Secondary Outcomes (8)

• Safety profile

  Up to approximately 10 months

• Overall Survival (OS)

  Up to approximately 25 months

• Best Overall Response Rate (BORR) Per RECIST1.1

  Up to approximately 10 months

• Depth of response (DpR)

  Up to approximately 10 months

• rate of secondary resection of metastases

  Up to approximately 10 months

Study Arms (2)

Experimental: Group A

EXPERIMENTAL

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.

Drug: Avastin, 25 Mg/mL Intravenous Solution

Active comparator: Group B

ACTIVE COMPARATOR

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.

Drug: Avastin, 25 Mg/mL Intravenous Solution

Interventions

Avastin, 25 Mg/mL Intravenous Solution 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.

Also known as: Experimental group, Control group

Active comparator: Group B; Experimental: Group A

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients aged ≥18 years.
• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Hospital, Tours: lead
• CHU DE BESANCON: collaborator
• Gustave Roussy, Cancer Campus, Grand Paris: collaborator
• CHU de Clermont-Ferrand: collaborator
• CHU de Reims: collaborator
• CHU de Brest: collaborator
• AP-HP, Hôpital Pitié- Salpétrière: collaborator
• University Hospital, Rouen: collaborator
• Poitiers University Hospital: collaborator
• Institut Paoli-Calmettes: collaborator
• Rennes University Hospital: collaborator
• University Hospital, Toulouse: collaborator
• AP-HP, Hôpital Saint-Louis: collaborator
• HCL Hôpital Edouard Hériot: collaborator
• Centre Hospitalier Universitaire Dijon: collaborator
• Nantes University Hospital: collaborator
• Centre Hospitalier Universitaire, Amiens: collaborator
• Hôpital Privé Jean Mermoz: collaborator
• AP-HP, Hôpital Henri Mondor: collaborator
• AP-HP, Hôpital Paul Brousse: collaborator
• CHG de St-Malo: collaborator
• Polyclinique de Blois: collaborator
• University Hospital, Caen: collaborator
• Central Hospital, Nancy, France: collaborator

MeSH Terms

Interventions

Bevacizumab; Control Groups

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Epidemiologic Research Design; Epidemiologic Methods; Investigative Techniques; Research Design; Methods

Study Officials

• Christophe Borg

  Besançon, FRANCE

  PRINCIPAL INVESTIGATOR

• Michel Ducreux

  Gustave Roussy, FRANCE

  PRINCIPAL INVESTIGATOR

• Caroline Petorin

  Clermont-Ferrand, FRANCE

  PRINCIPAL INVESTIGATOR

• Olivier Bouché

  Reims, FRANCE

  PRINCIPAL INVESTIGATOR

• Jean-Philippe Metges

  Brest, FRANCE

  PRINCIPAL INVESTIGATOR

• Jean-Baptiste Bachet

  Pitié- Salpétrière, FRANCE

  PRINCIPAL INVESTIGATOR

• Frédéric Di Fiore

  Rouen, FRANCE

  PRINCIPAL INVESTIGATOR

• David Tougeron

  Poitiers, FRANCE

  PRINCIPAL INVESTIGATOR

• Astrid Lièvre

  Rennes, FRANCE

  PRINCIPAL INVESTIGATOR

• Rosine Guimbaud

  Toulouse , FRANCE

  PRINCIPAL INVESTIGATOR

• Thomas Aparicio

  St Louis , FRANCE

  PRINCIPAL INVESTIGATOR

• Thomas Walter

  Edouard Hériot, FRANCE

  PRINCIPAL INVESTIGATOR

• Côme Lepage

  Dijon, FRANCE

  PRINCIPAL INVESTIGATOR

• Yann Touchefeu

  Nantes, FRANCE

  PRINCIPAL INVESTIGATOR

• Vincent Hautefeuille

  Amiens, FRANCE

  PRINCIPAL INVESTIGATOR

• Pascal Artru

  Jean Mermoz, FRANCE

  PRINCIPAL INVESTIGATOR

• Christophe Tournigand

  Henri Mondor, France

  PRINCIPAL INVESTIGATOR

• Pascal Hammel

  Paul Brousse, FRANCE

  PRINCIPAL INVESTIGATOR

• Romain Desgrippes

  St-Malo, FRANCE

  PRINCIPAL INVESTIGATOR

• Philippe Laplaige

  Blois, FRANCE

  PRINCIPAL INVESTIGATOR

• Karine Bouhier-Leporrier

  Caen, FRANCE

  PRINCIPAL INVESTIGATOR

• Marie Muller

  Nancy, france

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Thierry Lecomte

CONTACT

0247475900; thierry.lecomte@med.univ-tours.fr

Adeline MOUSSET

CONTACT

0218370645; a.fourmy@chu-tours.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

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

Study Record Dates

• First Submitted: March 8, 2024
• First Posted: October 15, 2024
• Study Start: October 30, 2024
• Primary Completion (Estimated): October 30, 2028
• Study Completion (Estimated): October 30, 2029
• Last Updated: October 15, 2024

Record last verified: 2024-10