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

Primary Purpose

Intrahepatic Cholangiocarcinoma

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Cisplatin-gemcitabine
Radiation: SIRT + chemotherapy (cisplatin-gemcitabine)
Sponsored by
Sirtex Medical
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Intrahepatic Cholangiocarcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Providence Health Care
  • Macquarie University Hospital
  • Peter MacCallum Cancer Centre
  • Cliniques Universitaires Saint-Luc
  • Hopital Beaujon
  • CHU Dijon
  • CHU de Grenoble
  • CHU Lyon - Hospital de la Croix-Rousse
  • Institut Paoli Calmettes
  • CHU Montpellier
  • CHU Nice - Hopital l'Archet 2
  • Hopital Haut-Leveque
  • CHU de Poitiers
  • Centre Eugene Marquis Hospital de Jour
  • Hopital Paul Brousse
  • U.O. Oncologia Medica 2 Universitaria
  • AMC Academic Medical Center
  • Hospital Clinic Barcelona
  • Clinica Universitaria de Navarra
  • Hammersmith Hospital Imperial College Healthcare NHS Trust
  • The Christie NHS Foundation Trust
  • Southampton General Hospital
  • The Clatterbridge Cancer Centre NHS Foundation Trust

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Chemotherapy (Cisplatin-Gemcitabine)

Radiation: SIRT + chemotherapy (Cisplatin-Gemcitabine)

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Survival at 18 months
Survival at 18 months is defined as the proportion of patients still alive 18 months from the date of randomization.

Secondary Outcome Measures

Liver-specific progression free survival (PFS)
Progression free survival (PFS) at any site
Objective response rate by RECIST 1.1 and refined RECIST - liver
Objective response rate by RECIST 1.1 and refined RECIST - at any site
Overall Survival
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.
Incidence of Adverse Events (Safety and tolerability)
Adverse events as assessed by CTCAE v. 4.0.

Full Information

First Posted
May 13, 2016
Last Updated
April 10, 2023
Sponsor
Sirtex Medical
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1. Study Identification

Unique Protocol Identification Number
NCT02807181
Brief Title
SIRT Followed by CIS-GEM Chemotherapy Versus CIS-GEM Chemotherapy Alone as 1st Line Treatment of Patients With Unresectable Intrahepatic Cholangiocarcinoma
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Completed
Study Start Date
January 2017 (Actual)
Primary Completion Date
October 2022 (Actual)
Study Completion Date
October 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sirtex Medical

4. Oversight

Studies a U.S. FDA-regulated Device Product
Yes
Data Monitoring Committee
Yes

5. Study Description

Brief 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.
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Intrahepatic Cholangiocarcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
89 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Chemotherapy (Cisplatin-Gemcitabine)
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Radiation: SIRT + chemotherapy (Cisplatin-Gemcitabine)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Cisplatin-gemcitabine
Other Intervention Name(s)
CIS-GEM
Intervention Description
Systemic chemotherapy
Intervention Type
Device
Intervention Name(s)
Radiation: SIRT + chemotherapy (cisplatin-gemcitabine)
Intervention Description
SIR-Spheres microspheres followed by systemic chemotherapy
Primary Outcome Measure Information:
Title
Survival at 18 months
Description
Survival at 18 months is defined as the proportion of patients still alive 18 months from the date of randomization.
Time Frame
18 months following the date of randomization.
Secondary Outcome Measure Information:
Title
Liver-specific progression free survival (PFS)
Time Frame
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..
Title
Progression free survival (PFS) at any site
Time Frame
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.
Title
Objective response rate by RECIST 1.1 and refined RECIST - liver
Time Frame
From the date of first treatment until the date of date of first documented progression in the liver, assessed up to 36 months.
Title
Objective response rate by RECIST 1.1 and refined RECIST - at any site
Time Frame
From the date of first treatment until progression at any site, assessed up to 36 months.
Title
Overall Survival
Time Frame
From date of randomization until the date of death from any cause, assessed up to 36 months.
Title
Liver surgical resection and ablation rate
Description
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.
Time Frame
18 months following the date of randomization.
Title
Incidence of Adverse Events (Safety and tolerability)
Description
Adverse events as assessed by CTCAE v. 4.0.
Time Frame
Informed consent until 28 days post last dose of protocol chemotherapy.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jordi Bruix, MD
Organizational Affiliation
Head of the Hepatic Oncology Unit, Hospital Clinic
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Harpreet Wasan, MD
Organizational Affiliation
Imperial College Healthcare Hammersmith Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Providence Health Care
City
Spokane
State/Province
Washington
ZIP/Postal Code
99204
Country
United States
Facility Name
Macquarie University Hospital
City
North Ryde
State/Province
New South Wales
ZIP/Postal Code
2109
Country
Australia
Facility Name
Peter MacCallum Cancer Centre
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3000
Country
Australia
Facility Name
Cliniques Universitaires Saint-Luc
City
Brussels
ZIP/Postal Code
1200
Country
Belgium
Facility Name
Hopital Beaujon
City
Clichy
ZIP/Postal Code
92110
Country
France
Facility Name
CHU Dijon
City
Dijon
ZIP/Postal Code
21079
Country
France
Facility Name
CHU de Grenoble
City
Grenoble
ZIP/Postal Code
38043
Country
France
Facility Name
CHU Lyon - Hospital de la Croix-Rousse
City
Lyon
ZIP/Postal Code
69317
Country
France
Facility Name
Institut Paoli Calmettes
City
Marseille
ZIP/Postal Code
13009
Country
France
Facility Name
CHU Montpellier
City
Montpellier
ZIP/Postal Code
34295
Country
France
Facility Name
CHU Nice - Hopital l'Archet 2
City
Nice
ZIP/Postal Code
06202
Country
France
Facility Name
Hopital Haut-Leveque
City
Pessac Cedex
ZIP/Postal Code
33604
Country
France
Facility Name
CHU de Poitiers
City
Poitiers
ZIP/Postal Code
86021
Country
France
Facility Name
Centre Eugene Marquis Hospital de Jour
City
Rennes
ZIP/Postal Code
35042
Country
France
Facility Name
Hopital Paul Brousse
City
Villejuif
ZIP/Postal Code
94800
Country
France
Facility Name
U.O. Oncologia Medica 2 Universitaria
City
Pisa
ZIP/Postal Code
56126
Country
Italy
Facility Name
AMC Academic Medical Center
City
Amsterdam
ZIP/Postal Code
1105
Country
Netherlands
Facility Name
Hospital Clinic Barcelona
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Facility Name
Clinica Universitaria de Navarra
City
Pamplona
ZIP/Postal Code
31008
Country
Spain
Facility Name
Hammersmith Hospital Imperial College Healthcare NHS Trust
City
London
ZIP/Postal Code
W12 0HS
Country
United Kingdom
Facility Name
The Christie NHS Foundation Trust
City
Manchester
ZIP/Postal Code
M20 4BX
Country
United Kingdom
Facility Name
Southampton General Hospital
City
Southampton
ZIP/Postal Code
S016 6YD
Country
United Kingdom
Facility Name
The Clatterbridge Cancer Centre NHS Foundation Trust
City
Wirral
ZIP/Postal Code
CH63 4JY
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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