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Biliary Tract Cancer (BTC)Phase 2/3CROCOBILNCT07437287

Testing Mitazalimab in Combination With Standard Chemotherapy in Immunotherapy Resistant Advanced Biliary Tract Cancers

A Phase 2/3 study testing mFOLFOX regimen and Mitazalimab in people with Biliary Tract Cancer (BTC), run by UNICANCER at 22 sites in France.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
Search all trials

Trial summary

The goal of this clinical trial is to etablish whether adding Mitazalimab to standard chemotherapy is more effective than standard chemotherapy alone in people with advanced bile duct cancer. It will also learn about the safety of Mitazalimab. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Biliary Tract Cancer (BTC)
What is being tested?
mFOLFOX regimen and Mitazalimab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
160 participants
Where
22 sitesFrance
Study dates
Jul 2026to Oct 2031
Phase
Phase 2/3
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age ≥18 years
  • Histologically-proven intrahepatic cholangiocarcinoma, extrahepatic (perihilar/distal) cholangiocarcinoma, or gallbladder carcinoma (ampullary carcinoma excluded)
  • Measurable tumor according to RECIST v1.1 classification
  • Non-resectable or metastatic disease or recurrent after surgery (if recurrence more than 6 months after adjuvant treatment stop)
  • Participants having received a standard first-line treatment (CISGEM + durvalumab or pembrolizumab) and eligible for second- or third-line treatment with FOLFOX. Participant could have received a previous targeted therapy in case of targetable alteration, but only one line of chemotherapy is permitted.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
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  • Adequate bone marrow reserve, normal renal and liver functions:
  • Neutrophil count ≥ 1500/mm³
  • Platelet count ≥ 150 000/mm³
  • Hemoglobin ≥ 10 g/dl
  • Estimated glomerular filtration rate (eGFR) value ≥50 mL/min using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation
  • Total bilirubin < 1.5 x ULN (after biliary stent placement in case of biliary obstruction)
  • No dihydropyrimidine dehydrogenase deficiency, as assessed by pre-treatment uracil blood level ≤ 16 ng/mL
  • Women of childbearing potential must have a negative serum or urine pregnancy test done within 7 days before randomization.
  • Participants must agree to use adequate contraception methods for the duration of study treatment and for within 15 months for women and 12 months for men after completing treatment.
  • Participants must be affiliated to a Social Security System (or equivalent).
  • Participant must have signed a written informed consent prior to any trial specific procedures. When the participant is physically unable to give their written consent, a trusted person of their choice, independent from the investigator or the sponsor, can confirm in writing the participant's consent.
  • Participants must be willing and able to comply with the protocol for the duration of the study including scheduled visits, treatment plan, laboratory tests and other study procedures.
  • Have archival tumor tissue sample that has been identified and confirmed as available
  • Participant having consented for a new tumor biopsy at inclusion for ancillary studies (participants with non-contributory new biopsy may still be included in the study).

Who cannot join

  • Participants having received previous treatment with fluoropyrimidine, oxaliplatin or CD40 agonist, except for capecitabine given as adjuvant treatment (if last administered > 6 months).
  • Concurrent malignancy (other than BTC), with the exception of adequately treated cone-biopsied in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin. Cancer survivors, who have undergone potentially curative therapy for a prior malignancy, have no evidence of that disease for 3 years or more and are deemed at negligible risk for recurrence, are eligible for the trial
  • Known CNS metastases or carcinomatous meningitis
  • History of chronic diarrhea, inflammatory disease of the colon or rectum, or unresolved partial or complete intestinal obstruction
  • History of myocardial infarction within 12 months of the first administration of mitazalimab, uncontrolled angina pectoris, unstable cardiac arrhythmias, or congestive heart failure of New York Heart Association class II or greater
  • QTc >450 msec
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  • Known history of HIV, hepatitis B or active hepatitis C infection
  • Toxicities from first-line treatment not resolved to Grade ≤ 1 (according to NCI-CTCAE v6.0) before randomization with the exception of alopecia
  • Contraindication to mitazalimab or to FOLFOX regimen, or their excipients
  • Prior toxicities of grade ≥ 3 with durvalumab or pembrolizumab (except from vitiligo, alopecia, hypothyroidism, adrenal insufficiency and diabetes) or other immune-related toxicities that led to definitive discontinuation
  • Has received attenuated vaccine within 28 days before the first dose of study treatment
  • Any condition which in the Investigator's opinion makes it undesirable for the participant to participate in the trial or which would jeopardize compliance with the protocol (including uncontrolled comorbidities, active infections or untreated central nervous system metastases)
  • Participation in another therapeutic trial within the 30 days prior to randomization
  • Pregnant women or women who are breast-feeding
  • Participant unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial, social, or psychological reasons
  • Individual deprived of liberty or placed under protective custody or guardianship.

Trial locations and contacts

22 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Nicolas DE SOUSA CARVALHO contact

+33 (0)1 71 93 67 09

n-de-sousa@unicancer.fr

22 sites in 1 country

France22 sites

  • Institut de cancérologie de l'Ouest - Site Paul Papin

    Angers, 49933

  • CHU de Bordeaux - Hopital Haut Leveque

    Bordeaux

  • CHU Brest

    Brest

  • Centre François Baclesse

    Caen

  • CHU Estaing

    Clermont-Ferrand

  • CHU de Dijon

    Dijon

  • CHU Grenoble Alpes

    Grenoble

  • CHU Lille

    Lille

  • Centre Léon Bérard

    Lyon

  • CHU de Lyon

    Lyon

  • APHM - CHU La Timone

    Marseille

  • CHU Montpellier - Hôpital Saint Eloi

    Montpellier

  • CHU Hotel Dieu

    Nantes

  • Hopital du Confluent

    Nantes

  • APHP - Hopital Beaujon

    Paris

  • Institut Curie

    Paris

  • CHU Poitiers

    Poitiers

  • Institut Jean Godinot

    Reims

  • Centre Eugène Marquis

    Rennes

  • Centre Paul Strauss

    Strasbourg

  • CHU Tours

    Tours

  • Institut de Cancérologie de Lorraine

    Vandœuvre-lès-Nancy

Other trials in France

About this study

Official title: Countering Immunotherapy Resistance With Novel Combinations in Advanced Biliary Tract Cancers

The goal of this clinical trial is to etablish whether adding Mitazalimab to standard chemotherapy is more effective than standard chemotherapy alone in people with advanced bile duct cancer. It will also learn about the safety of Mitazalimab.

The main questions it aims to answer are:

Read more
  • Does the addition of Mitazalimab enhance efficacy?
  • What medical problems do participants have when taking Mitazalimab + mFOLFOX?

Participants will:

  • Take drug mFOLFOX every two weeks until disease progression or mFOLFOX every two weeks plus mitazalimab in addition to mFOLFOX, with a first injection 7 days before the first mFOLFOX chemotherapy and then 3 days after the start of each mFOLFOX cycle.
  • Visit the clinic once every 2 weeks for checkups and tests
  • Have a radiological assessment every 8 weeks during treatment. After stopping treatment, participants will be monitored at the hospital every 8 weeks if no progression is observed, or every 12 weeks after disease progression.
Read the detailed description

Multicenter, open-label, randomized phase II/III trial evaluating the efficacity of mitazalimab in combination with mFOLFOX compared to mFOLFOX alone in participant advanced BTC

Being tested
mFOLFOX regimen, Mitazalimab
Keywords
Biliary Tract Cancer, Mitazalimab, Resistance to immunotherapy
Medical subject headings
Biliary Tract Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • mFOLFOX regimenDrug

    Also called Oxaliplatin, folinic acid and 5-FU

    oxaliplatin 85 mg/m² intravenous infusion (IV), folinic acid 400 mg/m² IV (or L-folinic acid 200 mg/m²), and fluorouracil (5-FU) 400 mg/m² IV bolus; followed by 5 FU 2400 mg/m² as a 46-hours continuous IV infusion:

    • every two week (14-day cycles) until disease progression on control arm
    • at D8 the first cycle and at D1 for subsequent cycles (14-day cycles) until disease progression on experimental arm

  • MitazalimabDrug

    Also called ADC-1013, JNJ-64457107

    The first cycle of treatment (21-day cycle): Mitazalimab 900 µg/kg by intravenous infusion (IV) at D1 and D10 Subsequent cycles (14-day cycles): Mitazalimab 900 µg/kg by intravenous infusion (IV) at D3 of each cycle until disease progression

Study groups in NCT07437287
Study groupRoleWhat they receive
Mitazalimab + mFOLFOXExperimentalNot described
Receives: Drug: mFOLFOX regimen; Drug: Mitazalimab
mFOLFOXActive comparatorNot described
Receives: Drug: mFOLFOX regimen

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 6 months overall survival rate of participants

    Proportion of participant still alive 6 months after randomisation

    Measured: From randomisation to 6 months after randomisation

Secondary outcomes (9)

  1. Safety of the treatments

    Adverse events will be collected and scored according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) common criteria v 6.0.

    This scale, divided into 5 grades (1 = "mild", 2 = "moderate", 3 = "severe", 4 = "life-threatening", and 5 = "death") determined by the investigator, will make it possible to assess the severity of the disorders.

    Measured: From inclusion to completion of the study, up to 64 months

  2. Objective response rate of participants (ORR)

    The objective response rate is defined as the percentage of participants with a complete response (CR) or a partial response (PR) on CT-scan for a given treatment

    Measured: Time from randomisation to disease progression, up to 64 months

  3. Disease control rate (DCR)

    Proportion of participants with stable disease, or partial response or complete response on CT-Scan

    Measured: Time from randomisation to disease progression, up to 64 months

  4. Progression-free survival (PFS)

    The Progression free survival is the lengh of time during and after the treatment of a disease that a patient lives with the disease but it does not get worse

    Measured: Time from randomisation to disease progression or death, up to 64 months

  5. Duration of overall response (DOR)

    Time from first documented response (compared to baseline measurement taken at randomisation) until the date of disease progression or death from any cause, whichever occurs first

    Measured: Time from randomisation to disease progression or death, up to 64 months

  6. Overall survival (OS)

    The overall survival is the length of time from randomization that patients enrolled in the study are still alive.

    Measured: From randomisation to death from any cause, up to 64 months

  7. Quality of life questionnaire - Core Function 17 (QLQ-F17)

    Developed by the EORTC, this self-reported questionnaire assesses the health-related quality of life of cancer patients in clinical trials. The questionnaire contains 15 items organized into five functional scales (physical, everyday activity, cognitive, emotional, and social) and 2 items for health/quality of life overall scale.

    The 15 items are rated on a four-point Likert-type scale (1 = "not at all", 2 = "a little", 3 = "quite a bit", and 4 = "very much") and are linearly transformed to a 0-100 scale, with higher scores indicating more severe symptoms.

    The 2 last items for health/quality of life overall are rated on 7 point scale (from 1 = "very poor" to 7 = "excellent")

    Measured: Baseline and every 2 months during the first year after randomisation

  8. Quality of life Questionnaire - Biliary tract cancer module (QLQ-BIL21)

    This EORTC cholangiocarcinoma and gallbladder cancer specific questionnaire is intended to supplement the QLQ-C30.

    The QLQ-BIL21 contains 21 items to assess symptoms. 3 single-item assessments relating to treatment side effects, difficulties with drainage bags/tubes and concerns regarding weight loss, and 18 items grouped into 5 scales: eating symptoms (4 items), jaundice symptoms (3 items), tiredness (3 items), pain symptoms (4 items) and anxiety symptoms (4 items). All items are rated on a four-point Likert-type scale (1 = "not at all", 2 = "a little", 3 = "quite a bit", and 4 = "very much"), and are linearly transformed to a 0-100 scale, with higher scores indicating more severe symptoms.

    Measured: Baseline and every 2 months during the first year after randomisation

  9. The Developed 5-level version of EQ-5D (EQ-5D-5L) questionnaire

    Developed by the EuroQol group, the self-reported questionnaire assesses the health-related quality of life of cancer patients in clinical trials consists of a descriptive system and a visual analogue scale (VAS).

    The EQ-5D-5L descriptive system comprises five dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), each dimension has 5 levels (1 = "no problems", 2 = "slight problems", 3 = "moderate problems", 4 = "severe problems", and 5 = "extreme problems"). This questionnaire provide a 5-digit score which generate a health state profile. The VAS records the patient's self-rated health on a vertical visual analogue scale where the score range from 0 (The best health you can image) to 100 (The worst health you can image). The VAS is used as a quantitative measure of health outcome that reflects the patient's own judgement.

    Measured: At Baseline and every 2 months during the first year after randomisation

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Feb 2026
  2. Study startJul 2026 (estimated)
  3. Primary completionApr 2030 (estimated)
  4. Study completionOct 2031 (estimated)

Resources

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 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
160 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07437287
Sponsor's protocol ID
UC-GIG-2519
Acronym
CROCOBIL
Status last verified
Feb 2026
First submitted
20 Feb 2026
Last updated
27 Feb 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing mFOLFOX regimen and Mitazalimab in people with Biliary Tract Cancer (BTC), run by UNICANCER at 22 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 20 inclusion and 16 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: opening soon, as of the sponsor's last update on 27 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 22 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 combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 Nicolas DE SOUSA CARVALHO (+33 (0)1 71 93 67 09, n-de-sousa@unicancer.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

6 months overall survival rate of participants (time frame: From randomisation to 6 months after randomisation). 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 NCT07437287.

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 27 Feb 2026.

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