Unresectable Metastatic Colorectal CancerPhase 3PHARBEVACOLNCT06642844
Bevacizumab-based Chemotherapy Adapted to Bevacizumab Pharmacokinetics in 1st-line Treatment
A Phase 3 study testing Avastin, 25 Mg/mL Intravenous Solution in people with Unresectable Metastatic Colorectal Cancer, run by University Hospital, Tours at 4 sites in France.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Unresectable Metastatic Colorectal Cancer
- What is being tested?
- Avastin, 25 Mg/mL Intravenous Solution
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 244 participants
- Where
- 4 sitesFrance
- Study dates
- 4 Mar 2025to 4 Mar 2029
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Show all 13Show fewer
- 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).
Who cannot join
- 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).
Show all 19Show fewer
- 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.
Trial locations and contacts
4 sites in 1 country. Contact the study team or a site near you to ask about taking part.
France4 sites, 4 recruiting
- Recruiting
BORG
Besançon
CHRISTOPHE BORG
- Not yet recruiting
Caroline Petorin
Clermont-Ferrand
- Not yet recruiting
Ducreux
Gustave Roussy
DUVREUX MICHEL
- Recruiting
David Tougeron
Poitiers
DAVID TOUGERON
About this study
Official title: 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.
Read the 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)
- Being tested
- Avastin, 25 Mg/mL Intravenous Solution
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Avastin, 25 Mg/mL Intravenous SolutionDrug
Also called Experimental group, Control group
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Avastin, 25 Mg/mL Intravenous Solution |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: up to death
Secondary outcomes (8)
Safety profile
Number of Participants Who Experienced an Adverse Event (AE) per NCI-CATCAE5.0 classification
Measured: Up to approximately 10 months
Overall Survival (OS)
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.
Measured: Up to approximately 25 months
Best Overall Response Rate (BORR) Per RECIST1.1
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.
Measured: Up to approximately 10 months
Depth of response (DpR)
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.
Measured: Up to approximately 10 months
rate of secondary resection of metastases
secondary resection of initially unresectable metastases of colorectal cancer
Measured: Up to approximately 10 months
Patient quality of life
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)
Measured: Up to approximately 10 months
Serum concentrations of bevacizumab
Serum concentrations of bevacizumab in order to evaluate the effect of doubling the administered dose of bevacizumab.
Measured: on day 14 of the first administration, and at 2 months from randomization (= 3 months from the first course)
Medical-economic analysis
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.
Measured: up to death
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Oct 2024
- Study start4 Mar 2025
- Primary completion4 Mar 2028 (estimated)
- Study completion4 Mar 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Unresectable Metastatic Colorectal CancerStudies of the same condition, open and under way.
- More trials run by University Hospital, ToursThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This project is a multicenter, double-blind, randomized trial in two parallel groups.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 244 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Tours
- Sponsor type
- University, hospital or other
- Collaborators
- CHU DE BESANCON, Gustave Roussy, Cancer Campus, Grand Paris, University Hospital, Clermont-Ferrand, CHU de Reims, CHU de Brest, Pitié-Salpêtrière Hospital, University Hospital, Rouen, Poitiers University Hospital, Institut Paoli-Calmettes, Rennes University Hospital, University Hospital, Toulouse, AP-HP, Hôpital Saint-Louis, HCL Hôpital Edouard Hériot, Centre Hospitalier Universitaire Dijon, Nantes University Hospital, Centre Hospitalier Universitaire, Amiens, Hôpital Privé Jean Mermoz, AP-HP, Hôpital Henri Mondor, Hopital Paul Brousse, CHG de St-Malo, Polyclinique de Blois, University Hospital, Caen, Central Hospital, Nancy, France
- Responsible party
- Sponsor
- Investigators
- Christophe Borg, Principal investigator, Besançon, FRANCEMichel Ducreux, Principal investigator, Gustave Roussy, FRANCECaroline Petorin, Principal investigator, Clermont-Ferrand, FRANCEOlivier Bouché, Principal investigator, Reims, FRANCEJean-Philippe Metges, Principal investigator, Brest, FRANCEJean-Baptiste Bachet, Principal investigator, Pitié- Salpétrière, FRANCEFrédéric Di Fiore, Principal investigator, Rouen, FRANCEDavid Tougeron, Principal investigator, Poitiers, FRANCE
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06642844
- Sponsor's protocol ID
- DR230009
- Acronym
- PHARBEVACOL
- Status last verified
- Jun 2026
- First submitted
- 8 Mar 2024
- Last updated
- 16 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT06642844
- Acronym / sponsor ID
- PHARBEVACOL / DR230009
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 244 participants (estimated)
- Lead sponsor
- University Hospital, ToursUniversity, hospital or other
- Collaborators
- CHU DE BESANCON, Gustave Roussy, Cancer Campus, Grand Paris, University Hospital, Clermont-Ferrand, CHU de Reims, CHU de Brest, Pitié-Salpêtrière Hospital, University Hospital, Rouen, Poitiers University Hospital, Institut Paoli-Calmettes, Rennes University Hospital, University Hospital, Toulouse, AP-HP, Hôpital Saint-Louis, HCL Hôpital Edouard Hériot, Centre Hospitalier Universitaire Dijon, Nantes University Hospital, Centre Hospitalier Universitaire, Amiens, Hôpital Privé Jean Mermoz, AP-HP, Hôpital Henri Mondor, Hopital Paul Brousse, CHG de St-Malo, Polyclinique de Blois, University Hospital, Caen, Central Hospital, Nancy, France
- Study start
- 4 Mar 2025 (actual)
- Primary completion
- 4 Mar 2028 (estimated)
- Study completion
- 4 Mar 2029 (estimated)
- First posted
- 15 Oct 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- This project is a multicenter, double-blind, randomized trial in two parallel groups.
| Arm | Type | Receives |
|---|---|---|
| Experimental: Group A | Experimental | Drug: Avastin, 25 Mg/mL Intravenous SolutionPatients 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. |
| Active comparator: Group B | Active comparator | Drug: Avastin, 25 Mg/mL Intravenous SolutionPatients 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. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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.
Key exclusion criteria (19 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Avastin, 25 Mg/mL Intravenous SolutionAlso: Experimental group, Control groupExperimental 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. | Drug | Active comparator: Group B, Experimental: Group A |
Primary outcome
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.
8 secondary outcomes
Safety profile
Time frame: Up to approximately 10 months
Overall Survival (OS)
Time frame: Up to approximately 25 months
Best Overall Response Rate (BORR) Per RECIST1.1
Time frame: Up to approximately 10 months
Depth of response (DpR)
Time frame: Up to approximately 10 months
rate of secondary resection of metastases
Time frame: Up to approximately 10 months
Patient quality of life
Time frame: 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)
Medical-economic analysis
Time frame: up to death
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jun 2026.
Related trials for Unresectable Metastatic Colorectal Cancer
RecruitingPhase 3
Pressurized Intraperitoneal Aerosolized Chemotherapy With Mitomycin for the Treatment of Unresectable Appendix or Colorectal Cancer With Peritoneal Metastases, The IMPACT Trial
Metastatic Appendix Carcinoma, Metastatic Colorectal Carcinoma
RecruitingPhase 2
A Study to Learn More About How Well Treatment With Sevabertinib (BAY 2927088) Tablets Works and How Safe it is in Participants Who Have a Solid Tumor With Mutations of the Human Epidermal Growth Factor Receptor 2 (HER2)
Advanced Solid Tumors, HER2 Mutation
RecruitingPhase 3
A Clinical Study of Calderasib (MK-1084) With Targeted Therapy and Chemotherapy in People With Colorectal Cancer (MK-1084-012/KANDLELIT-012)
Colon Adenocarcinoma, Rectal Adenocarcinoma
RecruitingPhase 3
A Study of Amivantamab and FOLFIRI Versus Cetuximab/Bevacizumab and FOLFIRI in Participants With KRAS/NRAS and BRAF Wild-type Colorectal Cancer Who Have Previously Received Chemotherapy
Colorectal Neoplasms
RecruitingPhase 1
A Study of JNJ-89402638 for Metastatic Colorectal and Gastric Cancers
Colorectal Neoplasms, Gastrointestinal Neoplasms
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Christophe Borg principal investigator
Besançon, FRANCE
Michel Ducreux principal investigator
Gustave Roussy, FRANCE
Caroline Petorin principal investigator
Clermont-Ferrand, FRANCE
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Avastin, 25 Mg/mL Intravenous Solution in people with Unresectable Metastatic Colorectal Cancer, run by University Hospital, Tours at 4 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 16 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Thierry Lecomte (0247475900, thierry.lecomte@med.univ-tours.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The primary endpoint is progression-free survival (PFS) (time frame: up to death). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jun 2026.