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

October 14, 2024 updated by: University Hospital, Tours

Bevacizumab-based Chemotherapy Tailored to the Pharmacokinetics of Bevacizumab in First-line Treatment of Unresectable Metastatic Colorectal Cancer: a Randomized, Multicenter, Double-blind Phase 3 Study

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

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)

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
244

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 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.
Drug: 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.

Other Names:
  • Control group
  • Experimental group
Active Comparator: 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.
Drug: 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.

Other Names:
  • Control group
  • Experimental group

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
The primary endpoint is progression-free survival (PFS)
Time Frame: up to death
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Safety profile
Time Frame: Up to approximately 10 months
Number of Participants Who Experienced an Adverse Event (AE) per NCI-CATCAE5.0 classification
Up to approximately 10 months
Overall Survival (OS)
Time Frame: Up to approximately 25 months
OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of analysis were censored at the date of last known contact.
Up to approximately 25 months
Best Overall Response Rate (BORR) Per RECIST1.1
Time Frame: Up to approximately 10 months
BORR is defined as the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started) assessed by the Response Evaluation Criteria in Solid Tumors (RECIST)v1.1. Complete Response (CR) is disappearance of all target lesions. Partial Response (PR) is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. Progressive Disease (PD) is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The appearance of one or more new lesions is also considered progressions). Stable Disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of diameters while on study.
Up to approximately 10 months
Depth of response (DpR)
Time Frame: Up to approximately 10 months
DpR was defined as the relative change in the sum of the target lesions' longest diameters at their smallest attained sizes compared to baseline time.
Up to approximately 10 months
rate of secondary resection of metastases
Time Frame: Up to approximately 10 months
secondary resection of initially unresectable metastases of colorectal cancer
Up to approximately 10 months
Patient quality of life
Time Frame: Up to approximately 10 months

Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 and European Quality of Life 5 Dimensions 5 Level Version questionnaires

Measure Description:

The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to 30 questions are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. Higher scores meant a better level of function.

The EQ-5D-5L is a generic tool for Patient-Reported Outcomes (PRO) measurement using 6 5 questions that can assess patients' quality of life, irrespective of the disease. .

It includes a vertical EQ visual analog scale (EQ VAS, 0-100 points)
Up to approximately 10 months
Serum concentrations of bevacizumab
Time Frame: on day 14 of the first administration, and at 2 months from randomization (= 3 months from the first course)
Serum concentrations of bevacizumab in order to evaluate the effect of doubling the administered dose of bevacizumab.
on day 14 of the first administration, and at 2 months from randomization (= 3 months from the first course)
Medical-economic analysis
Time Frame: up to death
A model-based cost-effectiveness analysis will be performed for estimating the Incremental Cost-Utility Ratio (cost per QALY gained) et the Incremental Cost-Effectiveness Ratio (cost per life-year gained) from the Healthcare system perspective.
up to death

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University Hospital, Tours

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Centre Hospitalier Universitaire Dijon
CHU de Reims
Centre Hospitalier Universitaire, Amiens
Poitiers University Hospital
University Hospital, Caen
Rennes University Hospital
University Hospital, Toulouse
Nantes University Hospital
Institut Paoli-Calmettes
Gustave Roussy, Cancer Campus, Grand Paris
CHU de Nancy
CHU de Brest
CHU DE BESANCON
CHU de Clermont-Ferrand
AP-HP, Hôpital Pitié- Salpétrière
CHU de Rouen
AP-HP, Hôpital Saint-Louis
HCL Hôpital Edouard Hériot
Hôpital Privé Jean Mermoz
AP-HP, Hôpital Henri Mondor
AP-HP, Hôpital Paul Brousse
CHG de St-Malo
Polyclinique de Blois

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: 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

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 30, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 30, 2028

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 30, 2029

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 8, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 14, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 15, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 15, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 14, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • DR230009

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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