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

Phase 2

Active, not recruiting

• Conditions: intrahepatic cholangiocarcinoma

• Registration Number: 2024-515660-31-00
• Lead Sponsor: Universitaetsklinikum Schleswig-Holstein AöR

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study First Posted: 2024-10-24
• Last Update Posted: 2025-04-29

Recruitment & Eligibility

• Status: Ongoing, recruitment ended
• Sex: Not specified
• Target Recruitment: 31

Inclusion Criteria

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 Criteria

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

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

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

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

Cirrhosis at a level of Child-Pugh B (or worse) or cirrhosis (any degree) and a history of hepatic encephalopathy or ascites

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

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

Female patients who are pregnant or breastfeeding

Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients

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

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 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

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 other concurrent antineoplastic treatment including chemotherapy, biologic or hormonal therapy or irradiation

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

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

History of allogenic organ transplantation

History of autologous/allogenic bone marrow transplant

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
R0/R1-resection rates		R0/R1-resection rates

Secondary Outcome Measures

Name	Time	Method
Pathological response rates, radiological resectability and response, safety and toxicity, 90-day perioperative morbidity, mortality and QoL		Pathological response rates, radiological resectability and response, safety and toxicity, 90-day perioperative morbidity, mortality and QoL

Trial Locations

Locations (5)

Universitaetsklinikum Regensburg AöR; 🇩🇪 Regensburg, Germany

Universitaetsklinikum Schleswig-Holstein AöR; 🇩🇪 Kiel, Germany

Uniklinik RWTH Aachen; 🇩🇪 Aachen,, Germany

University Medical Center Hamburg-Eppendorf; 🇩🇪 Hamburg, Germany

Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz KöR; 🇩🇪 Mainz, Germany

Universitaetsklinikum Regensburg AöR

🇩🇪Regensburg, Germany

Hans-Jürgen Schlitt

Site contact

00499419446801

hans.schlitt@ukr.de