Trial Title:
Testing Ivonescimab Versus FOLFOX in Advanced Biliary Tract Cancer Patients
NCT ID:
NCT06529718
Condition:
Biliary Tract Cancer
Conditions: Official terms:
Biliary Tract Neoplasms
Conditions: Keywords:
Biliary tract cancer
Gallbladder
Cholangiocarcinoma
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Ivonescimab
Description:
20 mg/kg IV infusion every 3 weeks
Arm group label:
Experimental
Intervention type:
Drug
Intervention name:
FOLFOX regimen
Description:
oxaliplatin 85 mg/m² IV, leucovorin 200 mg/m² IV (or folinic acid 400 mg/m²), and
fluorouracil (5-FU) 400 mg/m² IV bolus; followed by 5 FU 2400 mg/m² as a 46 hour
continuous IV infusion, every 2 weeks
Arm group label:
Control
Summary:
The object of this trial is to test whether ivonescimab is superior to standard
chemotherapy (FOLFOX regimen) for the treatment of patients with advanced biliary tract
cancer after failure of a first line of chemotherapy. It is only open to patients who
participated in the SAFIR-ABC10 trial (NCT05615818) but did not receive experimental
treatment.
Eligible patients will be randomised (2:1) to receive either ivonescimab or FOLFOX.
Treatment will be continued until disease progression, or a maximum of 34 cycles of
ivonescimab (experimental arm), whichever occurs first.
Detailed description:
This is a Phase 2, multicentre, randomised, two-arm, open-label trial to evaluate whether
ivonescimab is superior to standard second-line chemotherapy in the treatment of patients
with advanced biliary tract cancer.
The trial will be open to patients who participated in the screening phase of the
SAFIR-ABC10 protocol (NCT05615818) and who experienced disease progression on or
following the first-line standard of care (CISGEM regimen).
A total of 72 patients will be enrolled and randomly assigned (2:1) to receive treatment
with either:
- Experimental arm: Ivonescimab 20 mg/kg by intravenous infusion (IV) once every 3
weeks (Q3W).
- Control arm: Standard second-line chemotherapy - FOLFOX regimen Response to
treatment will be assessed according to RECIST v1.1 by radiographic exams performed
every 42 (±7) days. Patients will continue treatment until disease progression or
for a maximum of 34 cycles of ivonescimab (experimental arm), whichever occurs
first.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Signed a written informed consent form prior to any trial specific procedures.
2. Histologically-proven intrahepatic cholangiocarcinoma, perihilar / distal
cholangiocarcinoma, or gallbladder carcinoma (ampullary carcinoma excluded).
3. Locally advanced (non-resectable) or metastatic disease.
4. Participated in the Screening phase of the SAFIR-ABC10 trial.
5. Progression after first line standard of care (1L-SoC) regimen (CISGEM ±
immunotherapy) as assessed by the investigator.
6. Eligible for second-line treatment with FOLFOX.
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
8. Presence of at least one evaluable lesion according to RECIST v1.1.
9. Age ≥18 years.
10. Adequate bone marrow function: absolute neutrophil count (ANC) ≥2 × 10⁹/L, platelet
count ≥100 × 10⁹/L, and haemoglobin ≥9 g/dL.
Note: Blood transfusion or growth factor therapy should not be performed within 7
days prior to the screening haematology analysis.
11. Adequate liver function: total bilirubin level ≤1.5 × the upper limit of normal
(ULN) range (≤3 x ULN for patients with liver metastases or confirmed/suspected
Gilbert syndrome, and aspartate aminotransferase (AST) and alanine aminotransferase
(ALT) levels ≤2.5 × ULN (AST and ALT ≤5 x ULN when documented liver metastasis).
12. Adequate renal function: estimated creatinine clearance ≥50 mL/min according to the
Cockcroft-Gault formula, or estimated glomerular filtration rate value ≥50 mL/min
using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, and
urine protein < 2+ or 24 hour urine protein quantification < 1.0 g.
13. Coagulation: prothrombin time (PT) or international normalized ratio (INR) ≤ 1.5 x
ULN, and partial prothrombin time (PTT) or activated PTT ≤ 1.5 × ULN (unless
abnormalities are unrelated to coagulopathy,or prophylactic coagulation).
14. Adequate cardiac function: left ventricular ejection fraction (LVEF) ≥50% at
baseline as determined by either echocardiogram or multigated acquisition (MUGA)
scan.
15. Documented virology status of hepatitis, as confirmed by screening hepatitis B virus
(HBV) and hepatitis C virus (HCV) tests: For patients with active HBV: HBV DNA <500
IU/ml during screening, initiation of anti-HBV treatment at least 14 days prior to
randomization and willingness to continue anti-HBV treatment during the study (per
local standard of care; e.g., entecavir). For patients with HCV, either with
resolved infection (as evidenced by detectable antibody) or chronic infection (as
evidence by detectable HCV RNA), are eligible.
16. Performance of an esophagogastroduodenoscopy within 6 months of inclusion and
assessment and treatment of varices of all sizes per local standard of care prior to
randomisation.
17. Biliary tract obstruction has been relieved.
18. Adequate biliary drainage, with no evidence of ongoing infection.
19. Women of childbearing potential (WOCBP) having sex with an unsterilized male partner
and unsterilized males having sex with a female partner of childbearing potential,
must agree to use an effective method of contraception for the duration of trial
participation and as required after completing study treatment. Men must also agree
to not donate sperm and women must agree to not donate oocytes during the specified
period.
20. WOCBP must have a negative serum pregnancy test performed within 3 days before
randomisation and a negative urine pregnancy test on the day of first dose, prior to
treatment administration.
21. 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.
22. Affiliated to a social security system or in possession of equivalent private health
insurance (according to local regulations for participation in clinical trials).
Exclusion Criteria:
1. Toxicities from 1L-SoC not resolved to Grade ≤ 1 (according to version 5.0 of the
National Cancer Institute - Common terminology criteria for adverse events
[NCI-CTCAE v5.0]) before randomisation with the exception of alopecia.
2. Received first-line maintenance therapy with a matched target therapy proposed in
SAFIR ABC10, or any second-line treatment.
3. Contraindication to ivonescimab.
4. Proven complete deficiency of dihydropyrimidine dehydrogenase (DPD).
5. Treatment with brivudine, sorivudine or their chemical analogues in the 4 weeks
prior to randomisation.
6. Major surgical procedures or serious trauma within 4 weeks prior to randomisation,
or plans for major surgery within 4 weeks after the first dose (as determined by the
investigator). Minor local procedures (excluding central venous catheterisation and
port implantation) within 3 days prior to randomisation.
7. History of bleeding tendencies or coagulopathy and/or clinically significant
bleeding symptoms or risk within 4 weeks prior to randomisation, including but not
limited to:
1. Gastrointestinal bleeding.
2. Haemoptysis (defined as coughing up ≥ 0.5 teaspoon of fresh blood or small
blood clots).
Note: transient haemoptysis associated with diagnostic bronchoscopy is allowed.
3. Nasal bleeding /epistaxis (bloody nasal discharge is allowed).
4. Need for therapeutic anticoagulant therapy within 14 days prior to
randomization.
Note: Prophylactic anticoagulation for deep vein thrombosis or pulmonary embolism or
to maintain venous patency is allowed.
8. Current hypertension with systolic blood pressure ≥ 150 mmHg or diastolic blood
pressure ≥ 100 mmHg after oral antihypertensive therapy.
9. History of major diseases before randomization, specifically:
1. Unstable angina, myocardial infarction, congestive heart failure (New York
Heart Association classification ≥ grade 2) or vascular disease (eg, aortic
aneurysm at risk of rupture) that required hospitalization within 12 months
prior to randomization, or other cardiac impairment that may affect the safety
evaluation of the study drug (eg, poorly controlled arrhythmias, myocardial
ischemia),
2. History of oesophageal gastric varices, severe ulcers, wounds that do not heal,
abdominal fistula, intra-abdominal abscesses, or acute gastrointestinal
bleeding within 6 months before randomisation,
3. History of arterial thromboembolic event, venous thromboembolic event of Grade
3 and above as specified in NCI-CTCAE v5.0, transient ischemic attack,
cerebrovascular accident, hypertensive crisis, or hypertensive encephalopathy
within 6 months prior to randomization,
4. Acute exacerbation of chronic obstructive pulmonary disease within 4 weeks
before randomisation,
5. History of perforation of the gastrointestinal tract and/or fistula, history of
gastrointestinal obstruction (including incomplete intestinal obstruction
requiring parenteral nutrition), extensive bowel resection (partial colectomy
or extensive small bowel resection) within 6 months prior to randomisation.
10. Imaging during the screening period shows that the patient has:
1. Radiologically documented evidence of major blood vessel invasion or encasement
by cancer,
2. Radiographic evidence of intra-tumour cavitation.
11. Microsatellite instability positive disease.
12. Concurrent malignancy (other than advanced biliary tract cancer), 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 5 years or more and are deemed at negligible risk for recurrence, are
eligible for the trial.
13. HIV positive (HIV 1/2 antibodies patients), or a known history of active
Tuberculosis bacillus.
14. Any immunosuppressive therapy (i.e. corticosteroids >10mg of hydrocortisone or
equivalent dose) within 14 days before the planned start of study therapy.
15. Active autoimmune disease that has required a systemic treatment in past 2 years
(i.e. corticosteroids or immunosuppressive drugs). Replacement therapy (e.g.
thyroxine, insulin) is allowed active or history of autoimmune disease or immune
deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune
hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel
disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren
syndrome, Guillain-Barré syndrome, or multiple sclerosis, with the following
exceptions:
1. Patients with a history of autoimmune-related hypothyroidism who are on thyroid
replacement hormone are eligible for the study,
2. Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen
are eligible for the study,
3. Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with
dermatologic manifestations only (e.g., patients with psoriatic arthritis are
excluded) are eligible for the study provided all of following conditions are
met:
- Rash must cover < 10% of body surface area,
- Disease is well controlled at baseline and requires only low-potency
topical corticosteroids,
- No occurrence of acute exacerbations of the underlying condition requiring
psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic
agents, oral calcineurin inhibitors, or high potency or oral
corticosteroids within the previous 12 months.
16. Prior allogeneic bone marrow transplantation or prior solid organ transplantation.
17. Any condition which in the Investigator's opinion makes it undesirable for the
subject to participate in the trial or which would jeopardize compliance with the
protocol.
18. Pregnant or breast-feeding females.
19. Participation in another therapeutic trial within the 30 days prior to entering the
study. Participation in an observational trial would be acceptable.
20. Patients unwilling or unable to comply with the medical follow-up required by the
trial because of geographic, familial, social, or psychological reasons.
21. Individuals deprived of liberty or placed under protective custody or guardianship.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Cliniques universitaires Saint-Luc
Address:
City:
Brussels
Country:
Belgium
Facility:
Name:
Institute Mutualiste Montsouris
Address:
City:
Paris
Country:
France
Facility:
Name:
Centre Eugène Marquis
Address:
City:
Rennes
Country:
France
Facility:
Name:
University College London
Address:
City:
London
Country:
United Kingdom
Start date:
January 30, 2025
Completion date:
January 30, 2029
Lead sponsor:
Agency:
UNICANCER
Agency class:
Other
Collaborator:
Agency:
Cancer Research UK & UCL Cancer Trials Centre
Agency class:
Other
Collaborator:
Agency:
Belgian Group of Digestive Oncology
Agency class:
Other
Collaborator:
Agency:
Summit Therapeutics
Agency class:
Industry
Source:
UNICANCER
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06529718
