Trial Title:
Durvalumab + Intraductal Radiofrequency Ablation (ID-RFA) in Extrahepatic Cholangiocarcinoma
NCT ID:
NCT06440993
Condition:
Extrahepatic Cholangiocarcinoma
Unresectable Perihilar or Ductal CCA
Conditions: Official terms:
Cholangiocarcinoma
Gemcitabine
Durvalumab
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:
Gemcitabine
Description:
Gemcitabine, 1,000 mg/m2 IV
Arm group label:
systemic plus ID-RFA
Intervention type:
Drug
Intervention name:
Cisplatin
Description:
Cisplatin, 25 mg/m2 IV
Arm group label:
systemic plus ID-RFA
Intervention type:
Drug
Intervention name:
Durvalumab
Description:
Durvalumab, 1,500 mg IV
Arm group label:
systemic plus ID-RFA
Intervention type:
Procedure
Intervention name:
ID-RFA
Description:
endoscopic intraductal RFA
Arm group label:
systemic plus ID-RFA
Summary:
The present clinical trial is a prospective, investigator-initiated, single-arm,
open-label, multicenter phase II trial. Patients with unresectable perihilar and/or
ductal CCA with indication for bile duct stenting and palliative systemic therapy as
determined by the local multidisciplinary team (MDT), who already resolved cholestasis
due to RFA + Stent will be enrolled.
We hypothesize that in patients with extrahepatic cholangiocarcinoma, the use of a
combination radiofrequency ablation followed by systemic treatment with chemotherapy plus
durvalumab might further increase the anti-tumor activity.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Patient* has given written informed consent.
2. Patient is ≥ 18 years of age at time of signing the written informed consent.
3. Patient is willing and able to comply with the protocol for the duration of the
study including undergoing treatment and scheduled visits and examinations including
follow up.
4. Patient has been diagnosed with histologically or cytologically confirmed
1. histologically or cytologically confirmed cholangiocarcinoma as adenocarcinoma
of pancreatobiliary type
2. unresectable perihilar and/or ductal cholangiocarcinoma with indication for
bile duct stenting and palliative systemic therapy as determined by the local
multidisciplinary team (MDT) and already resolved cholestasis due to RFA +
stent
5. Patient tolerated RFA prior to inclusion and is eligible for repeat RFA during the
study (does not have any contraindications) as determined by investigator.
6. Patient is eligible for palliative systemic therapy based on clinical and laboratory
parameters (except hyperbilirubinemia) as determined by the local MDT
7. Patient has a ECOG ≤ 1.
8. Patient has life expectancy of ≥ 12 weeks
9. Patient has body weight > 30 kg
10. Adequate blood count, liver-enzymes, and renal function:
1. ANC > 1,500 cells/μL without the use of hematopoietic growth factors
2. Platelet count ≥ 100 x 109/L (>100,000 per mm3)
3. Hemoglobin ≥ 9 g/dL
4. Serum total bilirubin ≤ 3x upper normal limit (ULN) (biliary drainage is
allowed for biliary obstruction; elevated bilirubin should be caused by
obstruction not impaired liver function as assessed by albumin and INR values)
5. Albumin levels ≥ 2.8 g/dL
6. Patients not receiving therapeutic anticoagulation must have an INR< 2.0 ULN
and PTT < 1.5 ULN within 7 days prior to randomization. The use of full dose
anticoagulants is allowed as long as the INR or PTT is within therapeutic
limits (according to the medical standard in the institution) and the patient
has been on a stable dose for anticoagulants for at least three weeks at the
time of inclusion
7. AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional ULN unless liver metastases are
present, in which case it must be ≤ 5x ULN
8. Serum Creatinine ≤ 1.5 x ULN and a calculated creatinine clearance rate ≥ 60 mL
/min
11. Female patients defined as women of childbearing potential (WOCBP) or male patients
with WOCBP partners must agree to remain abstinent (refrain from heterosexual
intercourse) or use contraceptive methods that result in a failure rate of <1% per
year during the treatment period and for at least 6 months after the last dose of
chemotherapy or for at least 3 months after last dose of durvalumab, whatever
happens last. Male patients must refrain from donating sperm during this same
period. Male patients with a pregnant partner must agree to remain abstinent or to
use a condom for the duration of the pregnancy.
Exclusion Criteria:
1. Patient received previous or simultaneous endobiliary treatment other than RFA (e.g.
PDT or brachytherapy)
2. Patient received previous systemic therapy with a PD-1, PD-L1 inhibitor (including
durvalumab) or CTLA4 inhibitor or classical chemotherapy agents like platinum,
fluoropyrimidine or gemcitabine-based regimens.
3. Patient receives any concurrent chemotherapy, investigational product or hormonal
therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer
related conditions (e.g., hormone replace therapy) is acceptable.
4. Patient has known hypersensitivity to any component of the durvalumab formulation as
well as a known history of severe allergic, anaphylactic, or other hypersensitivity
reactions to chimeric or humanized antibodies or fusion protein and/or any known
contraindication (including hypersensitivity) to gemcitabine or cisplatin.
5. Patient has history of primary immunodeficiency
6. Patient has stage B cirrhosis according to Child-Pugh criteria (or worse) or
cirrhosis (of any grade) with a history of hepatic encephalopathy or clinically
significant ascites resulting from cirrhosis. Clinically significant ascites is
defined as ascites resulting from cirrhosis requiring diuretics or paracentesis.
7. Patient has any unresolved NCI CTCAE grade ≥ 2 from previous anticancer therapy with
the exception of alopecia, vitiligo, and laboratory values defined in the inclusion
criteria
1. Patients with grade ≥ 2 neuropathy will be evaluated on a case-by-case basis
after consultation with the Lead Investigator
2. Patients with irreversible toxicity not reasonably expected to be exacerbated
by treatment with durvalumab may be included only after consultation with the
Lead Investigator.
8. Patient had a prior allogeneic bone marrow transplantation or prior solid organ
transplantation.
9. Patient has active or history of autoimmune or inflammatory disorders (including,
but not limited to, 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]) . The following are
exceptions:
1. Patients with vitiligo or alopecia
2. Patients with hypothyroidism (e.g. following Hashimoto syndrome) stable on
hormone replacement
3. Patients with any chronic skin condition that does not require systemic therapy
4. Patients with celiac disease controlled by diet alone
5. Patients without active disease in the last 5 years may be included but only
after consultation with the Lead Investigator
10. Uncontrolled intercurrent illness, including but not limited to, ongoing or active
infection, symptomatic congestive heart failure, 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
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Universitätsklinikum Düsseldorf
Address:
City:
Düsseldorf
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Christoph Roderburg, Prof. Dr.
Facility:
Name:
Krankenhaus Nordwest
Address:
City:
Frankfurt
Zip:
60488
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Thorsten O Goetze, Prof. Dr.
Email:
goetze.thorsten@khnw.de
Facility:
Name:
Universitätsklinikum Köln
Address:
City:
Köln
Country:
Germany
Status:
Not yet recruiting
Contact:
Last name:
Dirk Waldschmidt, Dr.
Start date:
August 23, 2024
Completion date:
April 2028
Lead sponsor:
Agency:
Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
Agency class:
Other
Collaborator:
Agency:
Universitätsklinikum Düsseldorf, Germany
Agency class:
Other
Collaborator:
Agency:
Universitätsklinikum Köln, Germany
Agency class:
Other
Collaborator:
Agency:
AstraZeneca
Agency class:
Industry
Source:
Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06440993
