SIRT Followed by CIS-GEM Chemotherapy Versus CIS-GEM Chemotherapy Alone as 1st Line Treatment of Patients With Unresectable Intrahepatic Cholangiocarcinoma

Intrahepatic Cholangiocarcinoma Clinical Trial

— SIRCCA  

Official title:

Prospective, Multicenter, Randomized, Controlled Study Evaluating SIR-Spheres Y-90 Resin Microspheres Preceding Cisplatin-gemcitabine (CIS-GEM) Chemotherapy Versus CIS-GEM Chemotherapy Alone as First-line Treatment of Patients With Unresectable Intrahepatic Cholangiocarcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02807181
• Other study ID #: STX0115
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: January 2017
• Est. completion date: October 2022

Study information

• Verified date: April 2023
• Source: Sirtex Medical
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study will evaluate the benefit of applying Selective Internal Radiation Therapy (SIRT) using SIR-Spheres Y-90 resin microspheres prior to receiving systemic chemotherapy treatment (cisplatin-gemcitabine, or CIS-GEM) in patients with unresectable intrahepatic cholangiocarcinoma. Half of the patients will be randomized to CIS-GEM chemotherapy plus SIRT, and half of the patients will be randomized to CIS-GEM alone.

Description:

This clinical study is a prospective, multicenter, randomized, controlled study evaluating SIR-Spheres Y-90 resin microspheres followed by cisplatin-gemcitabine (CIS-GEM) chemotherapy vs. CIS-GEM chemotherapy alone as first-line treatment of patients with unresectable intrahepatic cholangiocarcinoma.

Randomized patients will be followed until death, withdrawal of consent, or until end of study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 89
• Est. completion date: October 2022
• Est. primary completion date: October 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Willing, able and mentally competent to provide written informed consent.

• Aged 18 years or older.

• Histologically or cytologically confirmed unresectable and non-ablatable intrahepatic cholangiocarcinoma.

• Liver-only or liver predominant intrahepatic cholangiocarcinoma. Patient are permitted to have loco-regional lymph node involvement defined as: portal LN </= to 2 cm and/or para aortic LN </= to 1.5 cm in longest diameter, and/or up to 2 indeterminate lung lesions < 1 cm if these lung lesions are positron emission tomography (PET) negative.

• Chemotherapy naïve. Adjuvant chemotherapy is not permitted.

• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.

• Adequate hematological function defined as:

Hemoglobin >/= 10g/dL White Blood Cell count (WBC) >/= 3.0 x 10^9/L Absolute neutrophil count (ANC) >/= 1.5 x 10^9/L Platelet count >/= 100,000/mm^3 - Adequate liver function defined as: Total bilirubin </= 30 umol/L (1.75 mg/dL) Albumin >/= 30 g/L

• Adequate renal function defined as: Serum urea and serum creatinine < 1.5 times upper limit of normal (ULN) Creatinine clearance >/= 45 ml/min (calculated with Cockcroft-Gault Equation)

• Life expectancy of at least 3 months without any active treatment

• Female patients must either be postmenopausal, sterile (surgically or radiation- or chemically-induced), or if sexually active use an acceptable method of contraception during the study.

• Male patients must be surgically sterile or if sexually active must use an acceptable method of contraception during the study.

• Considered suitable to receive either regimen in the clinical judgement of the treating investigator.

Exclusion Criteria:

• Patients with only non-measurable lesions in the liver according to RECIST criteria

• Incomplete recovery from previous liver surgery, e.g. unresolved biliary tree obstruction or biliary sepsis or inadequate liver function

• Biliary stent in situ

• Main trunk Portal Vein Thrombosis (PVT)

• Ascites, even if controlled with diuretics. (A minor peri-hepatic rim of ascites detected at imaging is acceptable).

• Mixed hepatocellular carcinoma - intrahepatic cholangiocarcinoma (HCC-ICC) disease

• History of prior malignancy. Exceptions include in-situ carcinoma of the cervix treated by cone-biopsy/resection, non-metastatic basal and/or squamous cell carcinomas of the skin, recurrent intra-hepatic cholangiocarcinoma post local treatment or any early stage (stage 1) malignancy adequately resected with curative intent at least 5 years prior to study entry

• Suspicion of any bone metastasis/metastases or central nervous system metastasis/metastases on clinical or imaging examination.

• Prior internal or external radiation delivered to the liver.

• Pregnancy; breast feeding.

• Participation within 28 days prior to randomization, in an active part of another clinical study that would compromise any of the endpoints of the study.

• Evidence of ongoing active infection that may affect treatment feasibility or outcome.

• Prior Whipple's procedure.

Related Conditions & MeSH terms

• Cholangiocarcinoma
• Intrahepatic Cholangiocarcinoma

Intervention

Drug:
• Cisplatin-gemcitabine
Systemic chemotherapy

Device:
• Radiation: SIRT + chemotherapy (cisplatin-gemcitabine)
SIR-Spheres microspheres followed by systemic chemotherapy

Locations

Country	Name	City	State
Australia	Peter MacCallum Cancer Centre	Melbourne	Victoria
Australia	Macquarie University Hospital	North Ryde	New South Wales
Belgium	Cliniques Universitaires Saint-Luc	Brussels
France	Hopital Beaujon	Clichy
France	CHU Dijon	Dijon
France	CHU de Grenoble	Grenoble
France	CHU Lyon - Hospital de la Croix-Rousse	Lyon
France	Institut Paoli Calmettes	Marseille
France	CHU Montpellier	Montpellier
France	CHU Nice - Hopital l'Archet 2	Nice
France	Hopital Haut-Leveque	Pessac Cedex
France	CHU de Poitiers	Poitiers
France	Centre Eugene Marquis Hospital de Jour	Rennes
France	Hopital Paul Brousse	Villejuif
Italy	U.O. Oncologia Medica 2 Universitaria	Pisa
Netherlands	AMC Academic Medical Center	Amsterdam
Spain	Hospital Clinic Barcelona	Barcelona
Spain	Clinica Universitaria de Navarra	Pamplona
United Kingdom	Hammersmith Hospital Imperial College Healthcare NHS Trust	London
United Kingdom	The Christie NHS Foundation Trust	Manchester
United Kingdom	Southampton General Hospital	Southampton
United Kingdom	The Clatterbridge Cancer Centre NHS Foundation Trust	Wirral
United States	Providence Health Care	Spokane	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Sirtex Medical

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  France,  Italy,  Netherlands,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Survival at 18 months	Survival at 18 months is defined as the proportion of patients still alive 18 months from the date of randomization.	18 months following the date of randomization.
Secondary	Liver-specific progression free survival (PFS)		From date of randomization to the first documented date of progression in the liver or date of death from any cause, assessed up to 36 months..
Secondary	Progression free survival (PFS) at any site		From date of randomization to the date of progression at any site until the first date of documented tumor progression at any site or date of death from any cause, assessed up to 36 months.
Secondary	Objective response rate by RECIST 1.1 and refined RECIST - liver		From the date of first treatment until the date of date of first documented progression in the liver, assessed up to 36 months.
Secondary	Objective response rate by RECIST 1.1 and refined RECIST - at any site		From the date of first treatment until progression at any site, assessed up to 36 months.
Secondary	Overall Survival		From date of randomization until the date of death from any cause, assessed up to 36 months.
Secondary	Liver surgical resection and ablation rate	To assess the number of patients in each arm who are downstaged by protocol therapy and can proceed to liver resection or ablation. The specific assessments will be the classification of resection as R0, R1 or R2, the presence of viable tumor or fibrosis, and the nearest resection margin.	18 months following the date of randomization.
Secondary	Incidence of Adverse Events (Safety and tolerability)	Adverse events as assessed by CTCAE v. 4.0.	Informed consent until 28 days post last dose of protocol chemotherapy.