Phase 2 Study of Preoperative Gemcitabine Plus Cisplatin with Durvalumab (MEDI4736) and Tremelimumab in intrahepatic cholangiocarcinoma (NeoTreme)

Trial details

Who runs it

Universitaetsklinikum Schleswig-Holstein AöR

Trial code

EU 2024-515660-31-00

Record updated

2025. december 18.

Original description

To demonstrate safety and feasibility of neoadjuvant Gemcitabine plus Cisplatin with Durvalumab and Tremelimumab in intrahepatic Cholangiocarcinoma by a R0/R1 resection rate > 65%.Read full original descriptionShow less

To demonstrate safety and feasibility of neoadjuvant Gemcitabine plus Cisplatin with Durvalumab and Tremelimumab in intrahepatic Cholangiocarcinoma by a R0/R1 resection rate > 65%.

Inclusion: Must have a life expectancy of at least 12 weeks; Body weight >30 kg; Adequate normal organ and marrow function as defined in the protocol; Women post-menopausal for more than two years can participate in the trial. Women with childbearing potential can only participate, if they are surgically sterile or a negative pregnancy test (serum) is available within 7 days before trial and they are willing to either be totally sexually abstinent OR practice at least one highly effective and medically accepted contraception method during trial (see chapter 7.1). They should have been stable on their chosen method of birth control for a minimum of 3 months before entering the study and continue to use it throughout the total duration of the drug treatment and the drug washout period (180 days after the last dose of durvalumab + tremelimumab and Gemcitabine/Cisplatin combination therapy); Men must agree to remain abstinent or use contraceptive measures, and agree to refrain from donating sperm, as defined: With female partners of childbearing potential or pregnant female partners, men must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of 1% per year during the treatment period and for at least 180 days after the last dose of study treatment to avoid exposing the embryo. Vasectomised males are considered fertile and should still use a male condom plus spermicide as indicated above during the clinical study; Ability of patient to understand nature, importance and individual consequences of clinical trial; Sufficient language skills to comprehend verbal and written information and capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol; Age >18 years; Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1; At least 1 lesion, not previously treated, that qualifies as a RECIST 1.1 target lesion (TL) at baseline. Tumor assessment by computed tomography (CT) scan or magnetic resonance imaging (MRI) must be performed within 28 days prior to treatment start; Histologically confirmed diagnosis of iCCA and available tumor tissue for translational research; Technical resectability of the primary tumor; No prior systemic or local therapy and no prior partial or complete tumor resection for iCCA.

Exclusion: Concurrent enrolment in another clinical study, unless it is an observational (non- interventional) clinical study prior to inclusion and during the study; Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.]). Few exceptions to this criterion are defined in the protocol; Any arterial thromboembolic events, including but not limited to myocardial infarction, transient ischemic attack, cerebrovascular accident, or unstable angina, within 6 months prior to enrollment. History of deep vein thrombosis, pulmonary embolism, or any other significant thromboembolism (venous port or catheter thrombosis or superficial venous thrombosis are not considered "significant") within 3 months of enrollment; Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab or tremelimumab. Few expeptions to this rule are described in the protocol; Receipt of live attenuated vaccine within 30 days prior to the first dose of IMP. Note: Patients, if enrolled, should not receive live vaccine whilst receiving IMP and up to 30 days after the last dose of IMP; Brain metastases or spinal cord compression. Patients with suspected brain metastases at screening should have a CT/ MRI of the brain prior to study entry; Any other concurrent antineoplastic treatment including chemotherapy, biologic or hormonal therapy or irradiation; Major surgical procedures, open biopsy or significant traumatic injury within 4 weeks prior to treatment start (minor procedures within 1 week); Prior radiation therapy within 14 days prior to study entry; Uncontrolled intercurrent illness, including but not limited to, symptomatic congestive heart failure (New York Heart Association Class III or IV), uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent or could compromise protocol objectives in the opinion of the Investigator and/or Sponsor; History of another primary malignancy (for exceptions see protocol); History of leptomeningeal carcinomatosis; History of active primary immunodeficiency; Active, uncontrolled bacterial, viral, or fungal infections, within 7 days of study entry requiring systemic therapy; Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen [HBsAg) result], hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA; Medical or psychological conditions that would jeopardize an adequate and orderly completion of the trial; Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients; Any co-existing medical condition that in the investigator’s judgement will substantially increase the risk associated with the patient’s participation in the study; Preexisting hearing impairment; History of allogenic organ transplantation; History of autologous/allogenic bone marrow transplant; Have Fridericia-corrected QT interval (QTcF) >470 msec (female) or >450 msec (male), or history of congenital long QT syndrome. Any ECG abnormality that in the opinion of the Investigator would preclude safe participation in the study; patients with pacemakers where QTc is not a reliable measure will require an evaluation by a cardiologist to exclude co-existing cardiac conditions which would prohibit safe participation in the study; Prior immunotherapy or use of other investigational agents, including prior treatment with an anti-Programmed Death receptor-1 (PD-1), anti-Programmed Death-1 ligand-1 (PD-L1), anti-PD-L2, or anti-cytotoxic T-lymphocyte associated antigen4 (anti-CTLA- 4) antibody, therapeutic cancer vaccines; Any unresolved toxicity NCI CTCAE (V5.0) Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria; Cirrhosis at a level of Child-Pugh B (or worse) or cirrhosis (any degree) and a history of hepatic encephalopathy or ascites; Female patients who are pregnant or breastfeeding; Distant metastases by CT or MRI of abdomen, pelvis, and thorax, bone scan or MRI (if bone metastases are suspected due to clinical signs). Infiltration of any adjacent organs or structures by CT or MRI, indicating an unresectable situation.

EU CTIS 2024-515660-31-00