Digestive CancerPhase 1/2BREGONCT02386397
Activity of Regorafenib in Combination With Chemotherapy in Patients With Advanced Biliary Tract Cancer
A Phase 1/2 study testing Regorafenib and GEMOX in people with Digestive Cancer, run by Institut du Cancer de Montpellier - Val d'Aurelle at 1 site in France.
Trial summary
This study is to determine the Regorafenib Dose (RD) for the phase II trial of Regorafenib administered in combination with mGEMOX in patients with advanced biliary tract cancer. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Digestive Cancer
- What is being tested?
- Regorafenib and GEMOX
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 66 participants
- Where
- 1 siteFrance
- Study dates
- Sep 2014to Dec 2019
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adenocarcinoma of the biliary tract
- Metastatic disease with no curative surgery option or metastatic recurrence after resection.
- Only for phase II: At least one measurable lesion in a non-irradiated area according to Response Evaluation Criteria in Solid Tumors
- No biliary obstruction.
- Age between 18 and 75 years.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
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- Life expectancy higher than 3 months.
- No prior chemotherapy for advanced disease. Previous adjuvant chemotherapy including Gemcitabine and/or platinum based is allowed if completed at least 6 months previously and relapsing after completion of the last dose.
- Total bilirubin ≤ 2.5 times the upper limit of the normal range. Patients with jaundice or evidence of bile duct obstruction, in whom the biliary tree can be decompressed by endoscopic or percutaneous endoprothesis (at least 15 days before inclusion) with subsequent reduction in total bilirubin ≤ 3 ULN, will be eligible for the study.
- Aminotransferases (AST, ALT) ≤ 2.5 ULN (≤ 5 ULN in case of diffuse hepatic involvement), INR < 1.5 (following vitamin K1 injection in patients with current or recent history of jaundice or bile duct obstruction), serum creatinine clearance calculated > 50 mL/min/1.73m² according to the Modification of Diet in Renal Disease (MDRD) formula, neutrophils ≥ 1.5.109/L, platelets ≥ 100.109/L, hemoglobin ≥ 9 g/dL (red blood cell transfusion is allowed if needed).
- Signed informed consent obtained before any study specific procedures.
- Patients must be affiliated to a Social Security System.
Who cannot join
- Known central nervous system metastases.
- Known history of human immunodeficiency virus (HIV) infection
- Contraindication or history of allergic reaction to one of the treatment components.
- Previous irradiation (external radiotherapy or brachytherapy) within 30 days prior to study treatment.
- Major surgery within 30 days prior to study treatment.
- Participation in another clinical trial within 30 days prior to study treatment.
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- Concomitant systemic immunotherapy, chemotherapy, antitumor hormone therapy, targeted therapy or any experimental therapy.
- Active uncontrolled infection, peripheral neuropathy grade ≥ 2, acute or subacute bowel obstruction, history of inflammatory bowel disease, interstitial pneumonitis, respiratory failure, renal failure, dysphagia or any malabsorption condition.
- Symptomatic coronary heart disease or myocardial infarction in the past 6 months, congestive heart failure (NYHA class II), prior cerebrovascular accident.
- Uncontrolled hypertension (systolic blood pressure (BP) > 150 mmHg or diastolic pressure > 90 mmHg despite optimal medical management).
- Proteinuria of National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) ≥ grade 2 (i.e. urinary protein ≥ 1.0 g/24 hrs).
- Patients with current or anticipated need for strong Cytochrome P450 3A4 (CYP3A4) inhibitors or inducers.
- Pregnancy (or positive β-HCG dosage at inclusion), breast-feeding, or lack of effective contraception in male or female patients of reproductive potential.
- Other malignancies either currently active or in the last 5 years, except adequately treated in situ carcinoma of the cervix and basal or squamous cell skin carcinoma.
- Legal incapacity or physical, psychological or mental status interfering with the patient's ability to sign the informed consent or to terminate the study
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Activity of Regorafenib in Combination With Modified Gemcitabine - Oxaliplatin Chemotherapy (mGEMOX) in Patients With Advanced Biliary Tract Cancer (BTC): A Phase Ib-II Trial (BREGO)
This study is to determine the Regorafenib Dose (RD) for the phase II trial of Regorafenib administered in combination with mGEMOX in patients with advanced biliary tract cancer.
Read the detailed description
Regorafenib (BAY 73-4506) was assessed in metastatic colorectal cancer in the phase III randomized CORRECT trial. 760 metastatic colorectal cancer patients were recruited after the failure of all standard therapies.
Given the promising efficacy and favorable tolerability profile of mGEMOX and the potential benefits of targeting the VEGF and Ras/Raf pathway, we propose to assess the combination of Regorafenib with mGEMOX in advanced digestive cancer.
This study is to determine the Regorafenib Dose (RD) for the phase II trial of Regorafenib administered in combination with mGEMOX in patients with advanced biliary tract cancer.
The phase I study of Regorafenib in advanced colorectal cancer showed a pronounced interindividual variability of drug exposition. Furthermore, the CORRECT study shows a large pharmacological variability of plasma concentration for Regorafenib and its metabolites. In this study, we propose to explore the pharmacological variability and his potential heritability by the therapeutic drug monitoring of Regorafenib. The objective is to understand and to control the pharmacological variability of Regorafenib and finally to predict the therapeutic response or the toxicity, especially in a population of patients with biliary tract cancer.
In addition, we will complete this study by exploring the gene variants of drug metabolism. The genes are POR (P450 OxidoReductase,) NR1I2 (Nuclear Receptor subfamily 1, group I, member 2) and a part of the regulatory sequences of CYP3A4.
- Conditions
- Digestive Cancer
- Being tested
- Regorafenib, GEMOX
- Medical subject headings
- Gastrointestinal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RegorafenibDrug
Also called Gemcitabin, Oxaliplatin
Regorafenib: X mg/d, PO, from day 1 to day 14; day 15 to day 20: off-treatment
GEMOXDrug
Also called Gemcitabine, Oxaliplatin
mGEMOX: infusion on days 1 and 8: Gemcitabine 900 mg/m² IV in 30 minutes Oxaliplatin 80 mg/m² IV in 120 minutes immediately after Gemcitabine
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | Regorafenib: X mg/d, PO, from day 1 to day 14; day 15 to day 20: off-treatment mGEMOX: infusion on days 1 and 8
* Gemcitabine 900 mg/m² IV in 30 minutes
* Oxaliplatin 80 mg/m² IV in 120 minutes immediately after Gemcitabine Receives: Drug: Regorafenib; Drug: GEMOX |
| Standard treatment | Other | mGEMOX: infusion on days 1 and 8
* Gemcitabine 900 mg/m² IV in 30 minutes
* Oxaliplatin 80 mg/m² IV in 120 minutes immediately after Gemcitabine Receives: Drug: GEMOX |
What is being measured
The primary outcome is the main question the study is designed to answer.
Limiting toxicity
To assess Limiting Toxicities during and within 6 weeks (2 cycles) after the beginning of the treatment.
Measured: up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Mar 2015 (estimated)
- Study startSep 2014
- Primary completionDec 2019
- Study completionDec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Digestive CancerStudies of the same condition, open and under way.
- More trials run by Institut du Cancer de Montpellier - Val d'AurelleThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 66 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- DOMERGUE Jacques, Study director, Institut régional du Cancer - Val d'Aurelle
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02386397
- Sponsor's protocol ID
- ICM2013/09
- Acronym
- BREGO
- Status last verified
- Mar 2026
- First submitted
- 2 Mar 2015
- Last updated
- 12 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Blanc JF, Bouattour M, Gauthier L, Deshayes E, Guillemard S, Touchefeu Y, Portales F, Borg C, Harguem L, Guimbaud R, Mineur L, Ychou M, Mazard T, Assenat E. Regorafenib plus modified gemcitabine-oxaliplatin in patients with advanced biliary tract cancer. The randomized phase Ib/II BREGO study. Oncologist. 2025 Jun 4;30(6):oyaf080. doi: 10.1093/oncolo/oyaf080.
PubMed 40542585
Study at a glance
From the registry record, last updated by the sponsor on 12 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Activity of Regorafenib in Combination With Modified Gemcitabine - Oxaliplatin Chemotherapy (mGEMOX) in Patients With Advanced Biliary Tract Cancer (BTC): A Phase Ib-II Trial (BREGO)
- ClinicalTrials.gov ID
- NCT02386397
- Acronym / sponsor ID
- BREGO / ICM2013/09
- Conditions
- Digestive Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 66 participants (actual)
- Lead sponsor
- Institut du Cancer de Montpellier - Val d'AurelleUniversity, hospital or other
- Study start
- Sep 2014 (actual)
- Primary completion
- Dec 2019 (actual)
- Study completion
- Dec 2019 (actual)
- First posted
- 11 Mar 2015 (estimated)
- 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.
This study is to determine the Regorafenib Dose (RD) for the phase II trial of Regorafenib administered in combination with mGEMOX in patients with advanced biliary tract cancer.
Detailed description
Regorafenib (BAY 73-4506) was assessed in metastatic colorectal cancer in the phase III randomized CORRECT trial. 760 metastatic colorectal cancer patients were recruited after the failure of all standard therapies.
Given the promising efficacy and favorable tolerability profile of mGEMOX and the potential benefits of targeting the VEGF and Ras/Raf pathway, we propose to assess the combination of Regorafenib with mGEMOX in advanced digestive cancer.
This study is to determine the Regorafenib Dose (RD) for the phase II trial of Regorafenib administered in combination with mGEMOX in patients with advanced biliary tract cancer.
The phase I study of Regorafenib in advanced colorectal cancer showed a pronounced interindividual variability of drug exposition. Furthermore, the CORRECT study shows a large pharmacological variability of plasma concentration for Regorafenib and its metabolites. In this study, we propose to explore the pharmacological variability and his potential heritability by the therapeutic drug monitoring of Regorafenib. The objective is to understand and to control the pharmacological variability of Regorafenib and finally to predict the therapeutic response or the toxicity, especially in a population of patients with biliary tract cancer.
In addition, we will complete this study by exploring the gene variants of drug metabolism. The genes are POR (P450 OxidoReductase,) NR1I2 (Nuclear Receptor subfamily 1, group I, member 2) and a part of the regulatory sequences of CYP3A4.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Drug: Regorafenib, Drug: GEMOXRegorafenib: X mg/d, PO, from day 1 to day 14; day 15 to day 20: off-treatment mGEMOX: infusion on days 1 and 8 * Gemcitabine 900 mg/m² IV in 30 minutes * Oxaliplatin 80 mg/m² IV in 120 minutes immediately after Gemcitabine |
| Standard treatment | Other | Drug: GEMOXmGEMOX: infusion on days 1 and 8 * Gemcitabine 900 mg/m² IV in 30 minutes * Oxaliplatin 80 mg/m² IV in 120 minutes immediately after Gemcitabine |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Adenocarcinoma of the biliary tract
- Metastatic disease with no curative surgery option or metastatic recurrence after resection.
- Only for phase II: At least one measurable lesion in a non-irradiated area according to Response Evaluation Criteria in Solid Tumors
- No biliary obstruction.
- Age between 18 and 75 years.
Key exclusion criteria (15 listed)
- Known central nervous system metastases.
- Known history of human immunodeficiency virus (HIV) infection
- Contraindication or history of allergic reaction to one of the treatment components.
- Previous irradiation (external radiotherapy or brachytherapy) within 30 days prior to study treatment.
- Major surgery within 30 days prior to study treatment.
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 |
|---|---|---|
| RegorafenibAlso: Gemcitabin, OxaliplatinRegorafenib: X mg/d, PO, from day 1 to day 14; day 15 to day 20: off-treatment | Drug | Treatment |
| GEMOXAlso: Gemcitabine, OxaliplatinmGEMOX: infusion on days 1 and 8: Gemcitabine 900 mg/m² IV in 30 minutes Oxaliplatin 80 mg/m² IV in 120 minutes immediately after Gemcitabine | Drug | Standard treatment, Treatment |
Primary outcome
Limiting toxicity
Time frame: up to 5 years
To assess Limiting Toxicities during and within 6 weeks (2 cycles) after the beginning of the treatment.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Mar 2026.
- Results publication: PubMed 40542585Blanc JF, Bouattour M, Gauthier L, Deshayes E, Guillemard S, Touchefeu Y, Portales F, Borg C, Harguem L, Guimbaud R, Mineur L, Ychou M, Mazard T, Assenat E. Regorafenib plus modified gemcitabine-oxaliplatin in patients with advanced biliary tract cancer. The randomized phase Ib/II BREGO study. Oncologist. 2025 Jun 4;30(6):oyaf080. doi: 10.1093/oncolo/oyaf080.
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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. This study is not recruiting at the moment.
DOMERGUE Jacques study director
Institut régional du Cancer - Val d'Aurelle
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Regorafenib and GEMOX in people with Digestive Cancer, run by Institut du Cancer de Montpellier - Val d'Aurelle at 1 site 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 12 inclusion and 15 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: finished, as of the sponsor's last update on 12 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Limiting toxicity (time frame: up to 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02386397, which also lists 1 linked publication.
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 12 Mar 2026.