Hepatic Arterial Infusion of Gemcitabine-Oxaliplatin for Second-Line Therapy in Non-Metastatic Unresectable Intra-Hepatic Cholangiocarcinoma: a Multicentric Single-Arm Phase Ii Study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Montpellier

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

29 Jan 2025 → ongoing

Decision date (initial)

2025-01-29

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-519132-17-00

EudraCT number

2017-002330-23

ClinicalTrials.gov

NCT03364530

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety

Evaluate the objective response rate (complete or partial response) 4 months after inclusion using RECIST 1.1 evaluation

Secondary objectives 5

1. • Safety (NCI-CTCAE )
2. • Quality of life (QLQ-C30)
3. Secondary resectability rate
4. • Overall survival
5. • Progression-free survival

Conditions and MedDRA coding

NON-METASTATIC UNRESECTABLE INTRA-HEPATIC CHOLANGIOCARCINOMA

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Histologically-proven intrahepatic cholangiocarcinoma previously treated by first-line systemic therapy
2. Absence of extra-hepatic metastasis or peritoneal carcinomatosis (as demonstrated by CTscan)
3. Age 18 years - General health status WHO PS 0 or 1 - Estimated life expectancy > 3 months
4. Disease that is not suitable for resection with a curative intent, as validated by a multidisciplinary committee with at least one senior hepatic surgeon
5. At least one measurable lesion according to RECIST 1.1 criteria
6. Platelets ≥100,000/mm3, polynuclear neutrophils ≥ 2000/mm3 , hemoglobin ³ 9g/dL (even transfused patients can be included) UF9794 CHU of MONTPELLIER Pr Boris GUIU Clinical Trial Protocol – Version 8, 03/01/2023 Page 13 sur 44 · Creatininemia < 1.5N · Creatinine clearance > 30mL/min · Bilirubinemia ≤2 N (after biliary drainage if necessary) · ASAT and ALAT ≤ 5N
7. Reference hepatic MRI (according to the foreseen protocol) done during the 30 days preceding the 1st cycle of treatment
8. · Women of child-bearing age using an adequate method of contraception throughout treatment and at least 4 months after discontinuation of Oxaliplatin · Women of childbearing age using an adequate method of birth control during treatment with Gemcitabine. · Men using an adequate method of contraception throughout the treatment and at least 6 months after the end of Oxaliplatin and after the end of Gemcitabine
9. · Written informed consent · National health insurance cover

Exclusion criteria 11

1. Patients with cholangiocarcinoma of the gallbladder or common bile duct or those with hepatocholangiocarcinoma or a Klatskin tumor
2. Patients who are eligible for surgical resection or liver transplantation · Extra-hepatic metastases [Pulmonary micronodules <7mm without uptake on PET are not a contra-indication] · Presence of clinical ascites
3. History of intra-arterial therapy or more than one line of systemic treatment
4. Contra-indication or grade 3-4 allergy to any of the treatment drugs Gemcitabine, Oxaliplatin (notably myelosuppression developped before the beginning of the first cycle of therapy, peripheral sensory neuropathy before the first cycle of therapy, severe renal failure)
5. peripheral neuropathy of grade 2 or higher · Patients with kalemia < lowest limit of normal · Patient withhypocalcemia · Patient with hypomagnesemia.
6. Ongoing participation or participation within the 21 days prior to inclusion in the study in another therapeutic trial with an experimental drug · Concomitant systemic treatment with immunotherapy, chemotherapy or hormone therapy · Serious non-stabilized disease, active uncontrolled infection or other serious underlying disorder likely to prevent the patient from receiving the treatment
7. Pregnancy (βHCG positive), breast-feeding or the absence of effective contraception for women of child-bearing age
8. Another cancer in the 5 years preceding or at the time of inclusion in the trial (except for in situ cervical cancer or basal cell carcinoma of the skin) · Allergy or contra-indication to iodine contrast agents (thyrotoxicosis, allergy to the active substance or excipients) · Treatment with anticoagulants (heparin or AVK) that cannot be interrupted for 12 hours · Treatment with anti-platelets that cannot be interrupted for 5 days for aspirin or Plavix.
9. Contra-indication for use of an intra-arterial approach (severe arteriopathy) · Contra-indication for implantation of the catheter: o Known infection: bacteremia or septicemia o Known allergy to any of the materials contained in the access port or catheter. o If the medications to be used in the access port are incompatible with any of the materials contained in the access port or catheter. o If the patient’s anatomy does not allow the insertion of the catheter into the chosen access site or if the patient has had previous radiotherapy in the chosen area. o Previous venous thrombosis. o Heparin induced thrombocytopaenia
10. Legal incapacity (persons in custody or under guardianship) · Deprived of liberty Subject (by judicial or administrative decision) · Impossibility to sign the informed consent document or to adhere to the medical follow-up of the trial for geographical, social or psychological reasons
11. Contraindication for the MRI: Pacemaker or neurosensorial stimulator or implantable defibrillator, cochlear implant, forromagnetic foreign body similar to the nervous structure. · The yellow fever vaccine and others live attenuated vaccines · ECG performed at baseline with a QT/QTc interval greater than 450 msec for men and greater than 470 msec for women

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is the percentage of patients with an objective response (defined as partial or complete response) 4 months after inclusion (using RECIST v1.1 criteria)

Secondary endpoints 5

1. Safety :NCI-CTCAE
2. Quality of life (QLQ-C30 questionnaire). The time to a final deterioration in the global health score (decrease of 5 points or more with no further improvement before death). The delay will be calculated from date of the first cycle to QoL evaluation or date of death or date of last news if the patient has no deterioration
3. Secondary resectability rate (as evaluated by an experienced hepatic surgeon)
4. Overall survival (estimated by the time between the date of inclusion and the date of death or date of last news for alive patients)
5. Progression-free survival by CT-scan/MRI according to the investigator's opinion (defined as the time between the date of inclusion and the date of first progression or death [whichever occurs first] or date of last news for patients alive without any progression)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Montpellier

Sponsor organisation

Centre Hospitalier Universitaire De Montpellier

Address

39 Avenue Charles Flahault

City

Montpellier Cedex 5

Postcode

34295

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Montpellier

Contact name

GUIU

Public contact point

Organisation

Centre Hospitalier Universitaire De Montpellier

Contact name

CADENE

Locations

1 EU/EEA country · 12 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications