Phase 2 Study of Preoperative Gemcitabine Plus Cisplatin with Durvalumab(MEDI4736) and Tremelimumab in intrahepatic cholangiocarcinoma(NeoTreme)
- Conditions
- C22.1Intrahepatic bile duct carcinoma
- Registration Number
- DRKS00032093
- Lead Sponsor
- niversitätsklinikum Schleswig-Holstein
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 31
1. Must have a life expectancy of at least 12 weeks.
2. Ability of patient to understand nature, importance and individual consequences of clinical trial.
3. Sufficient language skills to comprehend verbal and written information and capable of giving signed informed consent
4. Age >18 years.
5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
6. 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 treatment start
7. Histologically confirmed diagnosis of iCCA and available tumor tissue for translational research.
8. Technical resectability of the primary tumor.
9. No prior systemic or local therapy and no prior partial or complete tumor resection for iCCA.
10. Body weight >30 kg
11. Adequate normal organ and marrow function as defined below:
Absolute neutrophil count (ANC =1.5 × 109 /L), Hemoglobin =9 g/dL (transfusion permitted within 30 days of study entry), Platelet count =100 × 109/L, Serum bilirubin =2.0 x institutional upper limit of normal (ULN), Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =3x ULN, Creatinine normal for age: if serum creatinine is abnormal for age the patient must have a calculated creatinine clearance =50 mL/min using the CKD-EPI formula., Quick =70% or International normalized ratio (INR) = 1.2 x ULN
12. 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.
13. Men must agree to remain abstinent or use contraceptive measures, and agree to refrain from donating sperm, as defined in the protocol
1. Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study prior to inclusion and during the study.
2. Medical or psychological conditions that would jeopardize an adequate and orderly completion of the trial.
3. 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.
4. Any other concurrent antineoplastic treatment including chemotherapy, biologic or hormonal therapy or irradiation
- Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to study entry. Concurrent use of hormonal therapy for non-cancer-related conditions (eg, hormone replacement therapy) is acceptable.
5. 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
- Patients with Grade =2 neuropathy will be evaluated on a case-by-case basis after consultation with the medical monitor.
- Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab or tremelimumab may be included only after consultation with the medical monitor.
6. Major surgical procedures, open biopsy or significant traumatic injury within 4 weeks prior to treatment start (minor procedures within 1 week)
7. Prior radiation therapy within 14 days prior to study entry.
8. History of allogenic organ transplantation.
9. History of autologous/allogenic bone marrow transplant.
10. 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.]). The following are exceptions to this criterion:
a) Patients with vitiligo or alopecia
b) Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
c) Any chronic skin condition that does not require systemic therapy
d) Patients without active disease in the last 5 years may be included but only after consultation with the study physician
e) Patients with celiac disease controlled by diet alone
11. 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, 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.
12. Any arterial thromboembolic events, including but not limited to myocardial infarction, transient ischemic attack, cerebrovascular accident, or unstable angina, within 6 months prior to enrolment. History of deep vein thrombosis, pulmonary embolism, or any other significant thromboembolism (venous port or ca
Study & Design
- Study Type
- interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method resection rates (R0/R1) according to RECIST v1.1
- Secondary Outcome Measures
Name Time Method pathological response rates, impact on radiological resectability, radiological response, safety and toxicity, 90-day perioperative morbidity and mortality, quality of life