Clinical trial NCT02807181: SIRT Followed by CIS-GEM Chemotherapy Versus CIS-GEM Chemotherapy Alone as 1st Line Treatment of Patients With Unresectable Intrahepatic Cholangiocarcinoma
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Intrahepatic Cholangiocarcinoma
Lead sponsor: Sirtex Medical
Sponsor class: INDUSTRY
First posted: 2016-06-21
Enrollment: 89
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Survival at 18 Months
timeFrame: 18 months following the date of randomization.
Secondary outcomes:
measure: Liver-specific Progression Free Survival (PFS)
timeFrame: 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..
measure: Progression Free Survival (PFS) at Any Site
timeFrame: 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.
measure: Objective Response Rate by RECIST 1.1 and Refined RECIST - Liver
timeFrame: From the date of first treatment until the date of date of first documented progression in the liver, assessed up to 36 months.
measure: Objective Response Rate by RECIST 1.1 and Refined RECIST - at Any Site
timeFrame: From the date of first treatment until progression at any site, assessed up to 36 months.
measure: Overall Survival
timeFrame: From date of randomization until the date of death from any cause, assessed up to 36 months.
measure: Liver Surgical Resection and Ablation Rate
timeFrame: 18 months following the date of randomization.
measure: Incidence of Adverse Events (Safety and Tolerability)
timeFrame: Informed consent until 28 days post last dose of protocol chemotherapy.
Other outcomes:
Locations:
city: Spokane
country: United States
facility: Providence Health Care
state: Washington
city: North Ryde
country: Australia
facility: Macquarie University Hospital
state: New South Wales
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Clichy
country: France
facility: Hopital Beaujon
city: Dijon
country: France
facility: CHU Dijon
city: Grenoble
country: France
facility: CHU de Grenoble
city: Lyon
country: France
facility: CHU Lyon - Hospital de la Croix-Rousse
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Montpellier
country: France
facility: CHU Montpellier
city: Nice
country: France
facility: CHU Nice - Hopital l'Archet 2
city: Pessac Cedex
country: France
facility: Hopital Haut-Leveque
city: Poitiers
country: France
facility: CHU de Poitiers
city: Rennes
country: France
facility: Centre Eugene Marquis Hospital de Jour
city: Villejuif
country: France
facility: Hopital Paul Brousse
city: Pisa
country: Italy
facility: U.O. Oncologia Medica 2 Universitaria
city: Amsterdam
country: Netherlands
facility: AMC Academic Medical Center
city: Barcelona
country: Spain
facility: Hospital Clinic Barcelona
city: Pamplona
country: Spain
facility: Clinica Universitaria de Navarra
city: London
country: United Kingdom
facility: Hammersmith Hospital Imperial College Healthcare NHS Trust
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
city: Wirral
country: United Kingdom
facility: The Clatterbridge Cancer Centre NHS Foundation Trust
Study officials:
affiliation: Head of the Hepatic Oncology Unit, Hospital Clinic
name: Jordi Bruix, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Imperial College Healthcare Hammersmith Hospital
name: Harpreet Wasan, MD
role: PRINCIPAL_INVESTIGATOR
References: