Trial Title:
Neo-adjuvant Chemo and Immunotherapy in the Pre-operAtive Treatment of Locally Advanced CholangIOcarciNoma
NCT ID:
NCT06341764
Condition:
Cholangiocarcinoma
Conditions: Official terms:
Cholangiocarcinoma
Gemcitabine
Durvalumab
Tremelimumab
Antibodies, Monoclonal
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Durvalumab 1120 mg
Description:
Durvalumab 1120 mg day 1 i.v
Arm group label:
Single arm
Intervention type:
Drug
Intervention name:
Durvalumab 1500 mg
Description:
Durvalumab i.v. at 1500 mg once every 4 weeks
Arm group label:
Single arm
Intervention type:
Drug
Intervention name:
Tremelimumab i.v. at 300 mg
Description:
Single dose
Arm group label:
Single arm
Intervention type:
Combination Product
Intervention name:
Cisplatin (CDDP) 25 mg/mq i.v
Description:
Four cycles
Arm group label:
Single arm
Intervention type:
Combination Product
Intervention name:
Gemcitabine (GEM) 1000 mg/mq i.v.
Description:
Days 1 and 8 every 21 days
Arm group label:
Single arm
Summary:
Neoadjuvant chemo- and immunotherapy ameliorate the recurrence rate of cholangiocarcinoma
(CCA) at 12 months after surgery.
Detailed description:
Multicenter, single arm, phase II study
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- 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. Written informed consent and any locally required authorization (e.g.,
Health Insurance Portability and Accountability Act in the US, European Union [EU]
Data Privacy Directive in the EU) obtained from the patient/legal representative
prior to performing any protocol-related procedures, including screening
evaluations.
- Histologically or pathologically confirmed CCA
- Age >18 years at time of study entry.
- Eastern Cooperative Oncology Group (ECOG) 0 or 1.
- Locally advanced disease (as assessed in multidisciplinary sessions).
- Life expectancy of at least 16 weeks.
- Body weight >30 kg
- Adequate normal organ and marrow function as defined below: Haemoglobin ≥9.0 g/dL
- Absolute neutrophil count (ANC ≥1.5 × 109 /L)
- Platelet count ≥100 × 109/L
- Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN). This will not
apply to patients with confirmed Gilbert's syndrome (persistent or recurrent
hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or
hepatic pathology), who will be allowed only in consultation with their physician.
- AST (SGOT)/ALT (SGPT) ≤2.5 x institutional upper limit of normal unless liver
metastases are present, in which case it must be ≤5x ULN
- Measured creatinine clearance (CL) >40 mL/min or Calculated creatinine clearance
CL>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour
urine collection for determination of creatinine clearance.
- At least 1 lesion 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 randomization.
- No previous systemic or local treatments including radiation therapy, radiofrequency
ablations, electro-chemotherapy.
Exclusion Criteria:
- Any previous participation in another clinical interventional study.
- Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone
replacement therapy) is acceptable.
- History of allogenic organ transplantation.
- 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, interstitial lung disease, etc.]). The
following are exceptions to this criterion:
1. Patients with vitiligo or alopecia
2. Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on
hormone replacement
3. Any chronic skin condition that does not require systemic therapy
4. Patients without active disease in the last 5 years may be included but only
after consultation with the study physician
5. Patients with celiac disease controlled by diet alone
- Uncontrolled intercurrent illness, including but not limited to, ongoing or active
infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable
angina pectoris, history of myocardial infarction within 12 months, 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
- History of bowel obstruction, refractory ascites, or bowel perforation due to
advanced disease within the past 3 months from start of study treatment.
- Significant bleeding diathesis or coagulopathy. Serious, nonhealing wound, ulcer, or
current healing fracture.
- History of another primary malignancy except for
1. Malignancy treated with curative intent and with no known active disease ≥5
years before the first dose of IP and of low potential risk for recurrence
2. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence
of disease
3. Adequately treated carcinoma in situ without evidence of disease
- History of leptomeningeal carcinomatosis
- Brain metastases or spinal cord compression. Patients with suspected brain
metastases at screening should have an MRI (preferred) or CT each preferably with IV
contrast of the brain prior to study entry.
- History of active primary immunodeficiency.
- Known active hepatitis infection, positive hepatitis C virus (HCV) antibody,
hepatitis B virus (HBV) surface antigen (HBsAg) or HBV core antibody (anti-HBc), at
screening. Participants with a past or resolved HBV infection (defined as the
presence of anti HBc and absence of HBsAg) are eligible. Participants positive for
HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
- Known to have tested positive for human immunodeficiency virus (HIV) (positive HIV
1/2 antibodies) or active tuberculosis infection (clinical evaluation that may
include clinical history, physical examination and radiographic findings, or
tuberculosis testing in line with local practice).
- Current or prior use of immunosuppressive medication within 14 days before the first
dose of durvalumab or tremelimumab. The following are exceptions to this criterion:
Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra
articular injection
- Systemic corticosteroids at physiologic doses not to exceed <<10 mg/day>> of
prednisone or its equivalent
- Steroids as premedication for hypersensitivity reactions (e.g., CT scan
premedication)
- Receipt of live attenuated vaccine within 30 days prior to the first dose of IP.
- Female patients who are pregnant or breastfeeding or male or female patients of
reproductive potential who are not willing to employ effective birth control from
screening to 90 days after the last dose of durvalumab monotherapy or180 days after
the last dose of durvalumab and tremelimumab combination therapy.
- Known allergy or hypersensitivity to any of the study drugs or any of the study drug
excipients.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Istituto Nazionale Tumori di Napoli - IRCCS - Fondazione G. Pascale
Address:
City:
Napoli
Zip:
80131
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Alessandro Ottaiano
Phone:
08117770344
Email:
a.ottaiano@istitutotumori.na.it
Contact backup:
Last name:
Alessandro Ottaiano
Contact backup:
Last name:
Guglielmo Nasti
Contact backup:
Last name:
Francesco Izzo
Contact backup:
Last name:
Andrea Belli
Facility:
Name:
Ospedale Cardarelli, Napoli
Address:
City:
Napoli
Zip:
80131
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
Giovanni Vennarecci
Phone:
0817472372
Email:
giovanni.vennarecci@aocardarelli.it
Contact backup:
Last name:
Giovanni Vennarecci
Facility:
Name:
Università di Napoli "Federico II", Napoli
Address:
City:
Napoli
Zip:
80131
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
Roberto Bianco
Phone:
0817462061
Email:
robianco@unina.it
Contact backup:
Last name:
Roberto Bianco
Facility:
Name:
Ospedale san Camillo Forlanini/Spallanzani, Roma
Address:
City:
Roma
Zip:
00152
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
Viola Barucca
Phone:
3391333211
Email:
viola.barucca.scf@gmail.com
Contact backup:
Last name:
Viola Barucca
Facility:
Name:
Ospedale Mauriziano, Umberto I°
Address:
City:
Torino
Zip:
10128
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
Massimo Di Maio
Phone:
0115082032
Email:
massimo.dimaio@unito.it
Contact backup:
Last name:
Massimo Di Maio
Facility:
Name:
Università di Verona, Ospedale Borgoroma, Verona
Address:
City:
Verona
Zip:
37134
Country:
Italy
Status:
Not yet recruiting
Contact:
Last name:
Alessandra Auriemma
Phone:
3483148292
Email:
alessandra.auriemma@aovr.veneto.it
Contact backup:
Last name:
Alessandra Auriemma
Start date:
September 1, 2023
Completion date:
September 2025
Lead sponsor:
Agency:
National Cancer Institute, Naples
Agency class:
Other
Source:
National Cancer Institute, Naples
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06341764
