CholangiocarcinomaPhase 2NCT06341764
Neo-adjuvant Chemo and Immunotherapy in the Pre-operAtive Treatment of Locally Advanced CholangIOcarciNoma
A Phase 2 study testing Durvalumab 1120 mg, Durvalumab 1500 mg and Tremelimumab i.v. at 300 mg in people with Cholangiocarcinoma, run by National Cancer Institute, Naples at 6 sites in Italy.
Trial summary
Neoadjuvant chemo- and immunotherapy ameliorate the recurrence rate of cholangiocarcinoma (CCA) at 12 months after surgery. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cholangiocarcinoma
- What is being tested?
- Durvalumab 1120 mg, Durvalumab 1500 mg and Tremelimumab i.v. at 300 mg
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- 6 sitesItaly
- Study dates
- 1 Sep 2023to Sep 2025
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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:
- Patients with vitiligo or alopecia
- Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
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- Any chronic skin condition that does not require systemic therapy
- Patients without active disease in the last 5 years may be included but only after consultation with the study physician
- 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
- 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
- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
- 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.
Trial locations and contacts
6 sites in 1 country. Contact the study team or a site near you to ask about taking part.
6 sites in 1 country
Italy6 sites, 6 recruiting
- Recruiting
Istituto Nazionale Tumori di Napoli - IRCCS - Fondazione G. Pascale
Naples, Italia, 80131
Alessandro Ottaiano, 08117770344, a.ottaiano@istitutotumori.na.it
Alessandro Ottaiano
- Not yet recruiting
Ospedale Cardarelli, Napoli
Naples, Italia, 80131
Giovanni Vennarecci, 0817472372, giovanni.vennarecci@aocardarelli.it
Giovanni Vennarecci
- Not yet recruiting
Università di Napoli "Federico II", Napoli
Naples, Italia, 80131
Roberto Bianco, 0817462061, robianco@unina.it
Roberto Bianco
- Not yet recruiting
Ospedale san Camillo Forlanini/Spallanzani, Roma
Roma, Italia, 00152
Viola Barucca, 3391333211, viola.barucca.scf@gmail.com
Viola Barucca
- Not yet recruiting
Ospedale Mauriziano, Umberto I°
Torino, Italia, 10128
Massimo Di Maio, 0115082032, massimo.dimaio@unito.it
Massimo Di Maio
- Not yet recruiting
Università di Verona, Ospedale Borgoroma, Verona
Verona, Italia, 37134
Alessandra Auriemma, 3483148292, alessandra.auriemma@aovr.veneto.it
Alessandra Auriemma
About this study
Official title: Neo-adjuvant Chemo and Immunotherapy with Durvalumab (MEDI4736) and Tremelimumab (MEDI1123) in the Pre-operAtive Treatment of Locally Advanced CholangIOcarciNoma: an Exploratory and Translational Study.
Neoadjuvant chemo- and immunotherapy ameliorate the recurrence rate of cholangiocarcinoma (CCA) at 12 months after surgery.
Read the detailed description
Multicenter, single arm, phase II study
- Conditions
- Cholangiocarcinoma
- Being tested
- Durvalumab 1120 mg, Durvalumab 1500 mg, Tremelimumab i.v. at 300 mg, Cisplatin (CDDP) 25 mg/mq i.v, Gemcitabine (GEM) 1000 mg/mq i.v.
- Medical subject headings
- Cholangiocarcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Durvalumab 1120 mgDrug
Durvalumab 1120 mg day 1 i.v
Durvalumab 1500 mgDrug
Durvalumab i.v. at 1500 mg once every 4 weeks
Tremelimumab i.v. at 300 mgDrug
Single dose
Cisplatin (CDDP) 25 mg/mq i.vCombination product
Four cycles
Gemcitabine (GEM) 1000 mg/mq i.v.Combination product
Days 1 and 8 every 21 days
| Study group | Role | What they receive |
|---|---|---|
| Single arm | Experimental | Patient will receive four cycles of cisplatin (CDDP) 25 mg/mq i.v. and gemcitabine (GEM) 1000 mg/mq i.v. days 1 and 8 every 21 days, plus durvalumab 1120 mg day 1, followed (one week after the last dose of CDDP/GEM) by two administrations of durvalumab i.v. at 1500 mg once every 4 weeks and one administration of tremelimumab i.v. at 300 mg single dose. Premedication with antihistamines at standard doses can be applied. Receives: Drug: Durvalumab 1120 mg; Drug: Durvalumab 1500 mg; Drug: Tremelimumab i.v. at 300 mg; Combination Product: Cisplatin (CDDP) 25 mg/mq i.v; Combination Product: Gemcitabine (GEM) 1000 mg/mq i.v. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recurrence rate of CCA
To determine whether neoadjuvant chemo- and immunotherapy decrease the recurrence rate of CCA at 12 months after surgery.
Measured: 24 months
Secondary outcomes (6)
Rate of R0 resections
Rate of R0 resections (number of resections with surgical margins free from cancer/total number of resections) as assessed by pathologic examination (R1: microscopic disease.
Measured: 24 months
Radiologic responses
Radiologic responses evaluated through the RECIST v1.1 criteria.
Measured: 24 months
Pathologic responses
Pathologic responses (number of surgically removed tumour specimens with absence of any residual viable neoplastic cells).
Measured: 24 months
Toxicity assessed
Toxicity assessed by the NCI CTCAE v5.0
Measured: 24 months
PFS
Progression free survival (PFS) measured from study enrolment to death
Measured: 24 months
OS
Overall survival (OS) measured from study enrolment to death
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Apr 2024
- Study start1 Sep 2023
- Primary completionSep 2025 (estimated)
- Study completionSep 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CholangiocarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 38 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute, Naples
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Alessandro Ottaiano, Principal investigator, IRCCS I.N.T. "G. Pascale"
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06341764
- Sponsor's protocol ID
- CITATION
- Other IDs
- 7/23
- Status last verified
- Nov 2024
- First submitted
- 30 Oct 2023
- Last updated
- 7 Nov 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neo-adjuvant Chemo and Immunotherapy with Durvalumab (MEDI4736) and Tremelimumab (MEDI1123) in the Pre-operAtive Treatment of Locally Advanced CholangIOcarciNoma: an Exploratory and Translational Study.
- ClinicalTrials.gov ID
- NCT06341764
- Acronym / sponsor ID
- CITATION
- Conditions
- Cholangiocarcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 38 participants (estimated)
- Lead sponsor
- National Cancer Institute, NaplesUniversity, hospital or other
- Study start
- 1 Sep 2023 (actual)
- Primary completion
- Sep 2025 (estimated)
- Study completion
- Sep 2025 (estimated)
- First posted
- 2 Apr 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Neoadjuvant chemo- and immunotherapy ameliorate the recurrence rate of cholangiocarcinoma (CCA) at 12 months after surgery.
Detailed description
Multicenter, single arm, phase II study
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single arm | Experimental | Drug: Durvalumab 1120 mg, Drug: Durvalumab 1500 mg, Drug: Tremelimumab i.v. at 300 mg, Combination Product: Cisplatin (CDDP) 25 mg/mq i.v, Combination Product: Gemcitabine (GEM) 1000 mg/mq i.v.Patient will receive four cycles of cisplatin (CDDP) 25 mg/mq i.v. and gemcitabine (GEM) 1000 mg/mq i.v. days 1 and 8 every 21 days, plus durvalumab 1120 mg day 1, followed (one week after the last dose of CDDP/GEM) by two administrations of durvalumab i.v. at 1500 mg once every 4 weeks and one administration of tremelimumab i.v. at 300 mg single dose. Premedication with antihistamines at standard doses can be applied. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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).
Key exclusion criteria (27 listed)
- 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:
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Durvalumab 1120 mgDurvalumab 1120 mg day 1 i.v | Drug | Single arm |
| Durvalumab 1500 mgDurvalumab i.v. at 1500 mg once every 4 weeks | Drug | Single arm |
| Tremelimumab i.v. at 300 mgSingle dose | Drug | Single arm |
| Cisplatin (CDDP) 25 mg/mq i.vFour cycles | Combination product | Single arm |
| Gemcitabine (GEM) 1000 mg/mq i.v.Days 1 and 8 every 21 days | Combination product | Single arm |
Primary outcome
Recurrence rate of CCA
Time frame: 24 months
To determine whether neoadjuvant chemo- and immunotherapy decrease the recurrence rate of CCA at 12 months after surgery.
6 secondary outcomes
Rate of R0 resections
Time frame: 24 months
Radiologic responses
Time frame: 24 months
Pathologic responses
Time frame: 24 months
Toxicity assessed
Time frame: 24 months
PFS
Time frame: 24 months
OS
Time frame: 24 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Nov 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Alessandro Ottaiano principal investigator
IRCCS I.N.T. "G. Pascale"
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Durvalumab 1120 mg, Durvalumab 1500 mg and Tremelimumab i.v. at 300 mg in people with Cholangiocarcinoma, run by National Cancer Institute, Naples at 6 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 7 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Alessandro Ottaiano (08117770344, a.ottaiano@istitutotumori.na.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Recurrence rate of CCA (time frame: 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Nov 2024.