Neo-adjuvant Chemo and Immunotherapy in the Pre-operAtive Treatment of Locally Advanced CholangIOcarciNoma

NCT06341764 | Recruiting Phase 2

• 2 other identifiers: CITATION7/23
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 6

Brief Summary

Neoadjuvant chemo- and immunotherapy ameliorate the recurrence rate of cholangiocarcinoma (CCA) at 12 months after surgery.

Conditions

Cholangiocarcinoma

Outcome Measures

Primary Outcomes (1)

• Recurrence rate of CCA

  To determine whether neoadjuvant chemo- and immunotherapy decrease the recurrence rate of CCA at 12 months after surgery.

  24 months

Secondary Outcomes (6)

• Rate of R0 resections

  24 months

• Radiologic responses

  24 months

• Pathologic responses

  24 months

• Toxicity assessed

  24 months

• PFS

  24 months

Other Outcomes (2)

• Exploratory objectives

  24 months

• Exploratory objectives

  24 months

Study Arms (1)

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.

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.

Interventions

Durvalumab 1120 mg DRUG

Durvalumab 1120 mg day 1 i.v

Single arm

Durvalumab 1500 mg DRUG

Durvalumab i.v. at 1500 mg once every 4 weeks

Single arm

Tremelimumab i.v. at 300 mg DRUG

Single dose

Single arm

Cisplatin (CDDP) 25 mg/mq i.v COMBINATION_PRODUCT

Four cycles

Single arm

Gemcitabine (GEM) 1000 mg/mq i.v. COMBINATION_PRODUCT

Days 1 and 8 every 21 days

Single arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• National Cancer Institute, Naples: lead

Study Sites (6)

Istituto Nazionale Tumori di Napoli - IRCCS - Fondazione G. Pascale

Napoli, Italia, 80131, Italy

RECRUITING

Ospedale Cardarelli, Napoli

Napoli, Italia, 80131, Italy

NOT YET RECRUITING

Università di Napoli "Federico II", Napoli

Napoli, Italia, 80131, Italy

NOT YET RECRUITING

Ospedale san Camillo Forlanini/Spallanzani, Roma

Roma, Italia, 00152, Italy

NOT YET RECRUITING

Ospedale Mauriziano, Umberto I°

Torino, Italia, 10128, Italy

NOT YET RECRUITING

Università di Verona, Ospedale Borgoroma, Verona

Verona, Italia, 37134, Italy

NOT YET RECRUITING

MeSH Terms

Conditions

Cholangiocarcinoma

Interventions

durvalumab; Cisplatin; Gemcitabine

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Alessandro Ottaiano

  IRCCS I.N.T. "G. Pascale"

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Alessandro Ottaiano

CONTACT

08117770344; a.ottaiano@istitutotumori.na.it

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 30, 2023
• First Posted: April 2, 2024
• Study Start: September 1, 2023
• Primary Completion: September 1, 2025
• Study Completion: September 1, 2025
• Last Updated: November 7, 2024

Record last verified: 2024-11

Locations

IT (6)