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.
Overview
- Phase
- Phase 2
- Status
- Recruiting
- Sponsor
- National Cancer Institute, Naples
- Enrollment
- 38
- Locations
- 6
- Primary Endpoint
- Recurrence rate of CCA
Overview
Brief 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
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
- •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
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:
- •Patients with vitiligo or alopecia
- •Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
- •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
Arms & Interventions
Single arm
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.
Intervention: Durvalumab 1120 mg (Drug)
Single arm
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.
Intervention: Durvalumab 1500 mg (Drug)
Single arm
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.
Intervention: Tremelimumab i.v. at 300 mg (Drug)
Single arm
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.
Intervention: Cisplatin (CDDP) 25 mg/mq i.v (Combination Product)
Single arm
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.
Intervention: Gemcitabine (GEM) 1000 mg/mq i.v. (Combination Product)
Outcomes
Primary Outcomes
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.
Secondary Outcomes
- Toxicity assessed(24 months)
- Radiologic responses(24 months)
- Rate of R0 resections(24 months)
- Pathologic responses(24 months)
- PFS(24 months)
- OS(24 months)