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

NCT ID: NCT02807181

Last Updated: 2025-05-09

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 89 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-02-14
• Study Completion Date: 2021-04-29

Brief Summary

The study planned to 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 were randomized to CIS-GEM chemotherapy plus SIRT, and half of the patients were randomized to CIS-GEM alone.

Detailed Description

This clinical study was 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 were to be followed until death, withdrawal of consent, or until end of study.

Conditions

Intrahepatic Cholangiocarcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Chemotherapy (Cisplatin-Gemcitabine)

Cisplatin 25mg/m2 in 1000ml 0.9% saline given over 1 hour followed by 500 ml 0.9% saline over 30 minutes, followed by Gemcitabine 1000 mg/m2 in 250-500 ml 0.9% saline over 30 minutes by intravenous infusions on days 1, and 8 of a 21-day cycle.

Group Type: ACTIVE_COMPARATOR

Cisplatin-gemcitabine

Intervention Type: DRUG

Systemic chemotherapy

Radiation: SIRT + chemotherapy (Cisplatin-Gemcitabine)

A single treatment of hepatic arterial injection of SIR-Spheres Y-90 resin microspheres (SIRT) followed 14-16 days later by systemic chemotherapy (ABC-02 CIS-GEM protocol) with an intention to treat with 8 cycles of cisplatin + gemcitabine, or until progression, toxicity or patient choice. Treatment may be continued beyond 8 cycles in the absence of significant disease progression, at the treating clinicians' discretion.

Group Type: EXPERIMENTAL

Cisplatin-gemcitabine

Intervention Type: DRUG

Systemic chemotherapy

Radiation: SIRT + chemotherapy (cisplatin-gemcitabine)

Intervention Type: DEVICE

SIR-Spheres microspheres followed by systemic chemotherapy

Interventions

Cisplatin-gemcitabine

Systemic chemotherapy

Intervention Type: DRUG

Radiation: SIRT + chemotherapy (cisplatin-gemcitabine)

SIR-Spheres microspheres followed by systemic chemotherapy

Intervention Type: DEVICE

Other Intervention Names

CIS-GEM

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sirtex Medical

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jordi Bruix, MD

Role: PRINCIPAL_INVESTIGATOR

Head of the Hepatic Oncology Unit, Hospital Clinic

Harpreet Wasan, MD

Role: PRINCIPAL_INVESTIGATOR

Imperial College Healthcare Hammersmith Hospital

Locations

Providence Health Care

Spokane, Washington, United States

Macquarie University Hospital

North Ryde, New South Wales, Australia

Peter MacCallum Cancer Centre

Melbourne, Victoria, Australia

Cliniques Universitaires Saint-Luc

Brussels, , Belgium

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, , France

CHU de Poitiers

Poitiers, , France

Centre Eugene Marquis Hospital de Jour

Rennes, , France

Hopital Paul Brousse

Villejuif, , France

U.O. Oncologia Medica 2 Universitaria

Pisa, , Italy

AMC Academic Medical Center

Amsterdam, , Netherlands

Hospital Clinic Barcelona

Barcelona, , Spain

Clinica Universitaria de Navarra

Pamplona, , Spain

Hammersmith Hospital Imperial College Healthcare NHS Trust

London, , United Kingdom

The Christie NHS Foundation Trust

Manchester, , United Kingdom

The Clatterbridge Cancer Centre NHS Foundation Trust

Metropolitan Borough of Wirral, , United Kingdom

Southampton General Hospital

Southampton, , United Kingdom

Countries

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

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

STX0115

Identifier Type: -

Identifier Source: org_study_id