A Study of Sunitinib in Patients With Advanced Cholangiocarcinoma

NCT01718327 | Completed Phase 2

• 2 other identifiers: SUN-CK D09-22011-000073-30
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 6

Brief Summary

For patients with non-resectable cholangiocarcinoma, gemcitabine with cisplatin is considered as the reference treatment in first line chemotherapy. However, the outcomes of these patients remain limited and therefore more effective drugs are warranted. The context of the disease and current data on sunitinib suggest that sunitinib may have activity in patients with advanced non resectable cholangiocarcinoma. Thereby, it is proposed to conduct an open label single arm trial aiming evidencing activity of sunitinib in such a patient population.

Conditions

Unresectable and Advanced Cholangiocarcinoma

Keywords

Cholangiocarcinoma

Outcome Measures

Primary Outcomes (1)

• Overall survival

  to evaluate the overall survival of patients with advanced and unresectable cholangiocarcinoma treated continuously by sunitinib as second line at the dose of 37.5 mg per day, after one line of chemotherapy and to determine whether sunitinib deserves further studies in this indication.

  time interval from first sunitinib dose to the date of death as a result of any cause assessed up to 3 years

Secondary Outcomes (4)

• To evaluate the criteria of efficacy (PFS, ORR)

  time interval from first sunitinib dose to documented disease progression or death due to any cause, assessed up to 3 years after the beginning of the study

• To evaluate the effects of sunitinib on tumor angiogenesis

  Time interval from baseline to the end of treatment, an expected average of 6 months

• To characterize the safety profile of sunitinib (collection of AEs)

  Time interval from study entry to 1 month after last study drug administration, assessed up to 3 years after the beginning of the study, assessed up to 7 months after the beginning of the study

• To identify markers associated with response to sunitinib

  Time interval from baseline to the end of treatment, an expected average of 6 months

Study Arms (1)

open label, single arm

EXPERIMENTAL

single arm: sunitinib until progresion or unacceptable toxicity

Drug: Sunitinib

Interventions

Sunitinib DRUG

sunitinib dose :37.5mg/day

Also known as: sutent

open label, single arm

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent given according to ICH/GCP, and local regulation.
• Histologically or cytologically proven intrahepatic cholangiocarcinoma.
• Disease that is not amenable to surgery, radiation, or combined modality therapy with curative intent.
• Gemcitabine with or without platinum pre-treated patients with documented progression
• Local, locally-advanced or metastatic disease documented as having shown progression on a scan (CT, MRI).
• Measurable tumor according to RECIST criteria with at least one unidimensionally measurable target lesion
• No evidence of biliary duct obstruction unless obstruction controlled by local treatment or, in whom the biliary tree can be decompressed by endoscopic or percutaneous stenting with subsequent reduction in bilirubin £ 1.5xULN.
• Age between 18 and 80 years old
• Eastern Cooperative Oncology Group (ECOG) Performance Status :0-1
• Life expectancy ≥ 3 months.
• Ability to swallow oral compound.
• No acute toxic effects of previous treatment superior to grade to 1.
• Laboratory requirements:
• Hematologic: absolute neutrophil count (ANC) 1.5 x 103/mm3, platelets 100 x 103/mm3, hemoglobin 9 g/dl and Hepatic: Bilirubin \< 1.5 x upper normal limit (ULN), and alkaline phosphatase (AP) 5xULN. AST and ALT may be 5 x ULN Patients with jaundice Prothrombin time and partial thromboplastin time 1.7 xULN, serum albumin 2.8 g/dl. Renal: Serum creatinine 1.5 xULN , and clearance \> 60 ml/min.
• Normal cardiovascular function

You may not qualify if:

• Hilar cholangiocarcinomas, cholangiocarcinomas located in the gall bladder, hepatic capsule effraction, extrahepatic primary cholangiocarcinoma, carcinoma of the Water ampullum.
• Prior treatment with other chemotherapy than gemcitabine and/or platinum.
• Concomitant treatment with any chemotherapy, chemoembolization therapy, immunotherapy, antitumoral hormonotherapy or investigational anticancer agents..
• Prior treatment with any tyrosine kinase inhibitors or anti-VEGF angiogenic inhibitors.
• Diagnosis of any second malignancy within the last 5 years, except for adequately treated basal cell or squamous cell skin cancer, or in situ carcinoma of the cervix uteri.
• Treatment with potent CYP3A4 inhibitors and inducers within 7 and 12 days, respectively prior to study drug administration.
• Pre-existing thyroid abnormality of thyroid function that cannot be maintained in the normal range with medication.
• Concomitant treatment with therapeutic doses of anticoagulants (low dose warfarin (Coumadin) up to 2 mg PO daily for deep vein thrombosis prophylaxis is allowed).
• Unstable systemic diseases including uncontrolled hypertension (\>150/100 mmHg despite optimal medical therapy) or active uncontrolled infections.
• Drug having proarrhythmic potential (terfenadine, quinidine,procainamide, disopyramide, sotalol, probucol, bepridil, haloperidol, risperidone, indapamide and flecainide).
• Any of the following within the 12 months prior to study drug administration: myocardial infarction, severe/unstable angina, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, or pulmonary embolism.
• Abnormal cardiac function with abnormal 12 lead ECG. Ongoing cardiac dysrhythmias of NCI CTC grade2, atrial fibrillation of any grade, or prolongation of the QTc interval to \>450 msec for males or \>470 msec for females.
• Symptomatic brain metastases, spinal cord compression, or new evidence of brain or leptomeningeal disease.
• Current treatment with any other investigational medicinal product.
• Positive test for human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness

Sponsors & Collaborators

• GERCOR - Multidisciplinary Oncology Cooperative Group: lead

Study Sites (6)

Hôpital Beaujon

Clichy, 92118, France

Location

Hôpital privé Jean Mermoz

Lyon, 69008, France

Location

CHU La Timone

Marseille, 13005, France

Location

Hôpital Saint Antoine

Paris, 75012, France

Location

Institut Mutualiste Montsouris

Paris, 75014, France

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

Related Publications (2)

• Gros L, Bouattour M, Dumont C, Dahan L, Malka D, Tijeras-Raballand A, De Gramont A, Ronot M, Dreyer C, Neuzillet C, Bourget P, Hadengue A, Roldan N, Garcia-Larnicol ML, Chibaudel B, Raymond E, Faivre S. Sunitinib as Second-Line Treatment in Advanced Intrahepatic Cholangiocarcinoma: Results From the SUN-CK GERCOR Phase II Trial. Liver Int. 2025 Aug;45(8):e70196. doi: 10.1111/liv.70196.

  PMID: 40631456 DERIVED

• Dreyer C, Sablin MP, Bouattour M, Neuzillet C, Ronot M, Dokmak S, Belghiti J, Guedj N, Paradis V, Raymond E, Faivre S. Disease control with sunitinib in advanced intrahepatic cholangiocarcinoma resistant to gemcitabine-oxaliplatin chemotherapy. World J Hepatol. 2015 Apr 28;7(6):910-5. doi: 10.4254/wjh.v7.i6.910.

  PMID: 25937868 DERIVED

MeSH Terms

Conditions

Cholangiocarcinoma

Interventions

Sunitinib

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Sandrine Faivre, MD/PhD

  Hôpital Beaujon

  PRINCIPAL INVESTIGATOR

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 22, 2012
• First Posted: October 31, 2012
• Study Start: September 1, 2011
• Primary Completion: November 17, 2016
• Study Completion: November 17, 2016
• Last Updated: January 31, 2017

Record last verified: 2017-01

Locations

FR (6)