Selective Internal Radiation Therapy and Capecitabine (Chemotherapy) Treatment for Liver Cancer (SIROCHO)
Primary Purpose
Resectable Intrahepatic Cholangiocarcinoma
Status
Recruiting
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Capecitabine
Selective Internal Radiotherapy (SIRT)
Surgery
Sponsored by
About this trial
This is an interventional treatment trial for Resectable Intrahepatic Cholangiocarcinoma focused on measuring Selective Internal Radiation Therapy
Eligibility Criteria
Inclusion Criteria:
- Age > 18 years-old,
- ECOG Performance Status <2,
- Histologically-proven ICC,
- No previous treatment,
- Tumour deemed resectable by a hepatobiliary surgeon, validated by a Surgical Review Board,
Significant risk of close margins, defined as:
- Resection margin predicted by the surgeon <1 cm
- Tumour >5 cm
- Multifocal lesion deemed resectable, validated by a Surgical Review Board
- Registration with a social security scheme,
- Patient information and signature of informed consent or legal representative.
Non-inclusion Criteria:
- Cirrhosis,
Inadequate haematological, hepatic, renal and coagulation functions:
- Haemoglobin ≤ 8,5 g/dl
- Neutrophils < 1,5 Giga/L
- Platelets < 60 Giga/L
- Bilirubin > 34 µmol/L
- ASAT/ALAT > 5 x ULN
- Creatinine clearance < 30 ml/min (MDRD)
- TP et INR > 2,3 ULN
- TCA > 1,5 x ULN
- Uracil blood level >16 ng/mL,
- Respiratory insufficiency,
- Comorbidity precluding surgical resection, such as severe heart disease,
- Contraindication to hepatic artery catheterization (vascular abnormalities, bleeding diathesis),
- Other invasive malignancies in the past 3 years,
- Patient participate to an interventional study that tests another medical intervention before surgery,
- Pregnant woman or likely to be or breastfeeding, or male or female patients of reproductive potential without effective contraception from screening to 30 days after the end of the treatment adjuvant,
- Minors, individual deprived of liberty, or under any kind of guardianship,
- Patients unable to submit to medical follow-up of the study for social, medical or psychological reasons.
Exclusion Criteria:
- Pulmonary shunt with dose >30Gy,
- Digestive shunting, non-correctible by interventional radiology,
- Absence of fixation of MAA in the tumour.
Sites / Locations
- Centre de Lutte contre le Cancer Eugène MarquisRecruiting
- Hôpital BeaujonRecruiting
- Hôpital Henri - Mondor
- Groupe SUD-Haut-Lévêque - Centre Hospitalier Universitaire de BordeauxRecruiting
- Centre Hospitalier Universitaire de Montpellier
- Centre Hospitalier Universitaire de Poitiers
- Gustave RoussyRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Other
Arm Label
Capecitabine combined with SIRT
Surgery only
Arm Description
Patients in the experimental arm will be treated with capecitabine combined with Selective Internal Radiotherapy (SIRT) before surgery.
Patients in the control group will receive surgery only.
Outcomes
Primary Outcome Measures
Frequency of subjects with adequate surgical margins
The primary endpoint will be the frequency of subjects with adequate surgical margins, defined as the number of resections AND margin ≥ 5mm.
Secondary Outcome Measures
Full Information
NCT ID
NCT05265208
First Posted
January 25, 2022
Last Updated
August 22, 2023
Sponsor
Center Eugene Marquis
1. Study Identification
Unique Protocol Identification Number
NCT05265208
Brief Title
Selective Internal Radiation Therapy and Capecitabine (Chemotherapy) Treatment for Liver Cancer
Acronym
SIROCHO
Official Title
A Multicenter Open-label Randomized Controlled Prospective Phase II Study Evaluating the Efficacy of Selective Internal Radiation Therapy (Yttrium-90 Glass Microspheres) Combined With Capecitabine in the Neoadjuvant Setting of Operable Intrahepatic CHOlangiocarcinoma
Study Type
Interventional
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 4, 2022 (Actual)
Primary Completion Date
September 4, 2025 (Anticipated)
Study Completion Date
February 4, 2028 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Center Eugene Marquis
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Treatment of intrahepatic cholangiocarcinoma (ICC) remains difficult. Many patients have unresectable tumors, and survival after resection was only slightly improved with the use of adjuvant capecitabine. One of the major prognostic factors is the resection margin, patients with invaded (R1) or narrow (<5mm) margins having a higher risk of recurrence.
Selective Internal Radiation Therapy (SIRT) with Yttrium-90 microspheres (also known as SIRT) is an interesting treatment in unresectable ICC. In a phase 2 study, the investigators showed a response rate of 39% and a disease control rate of 98%. Interestingly, 9 of the 41 patients were able to see their tumors downstages to surgery. It was also recently suggested in a retrospective study that patients resected after SIRT had a better prognosis than patients that could be operated upfront, despite less favorable initial tumor characteristics.
Given the absence of validated neoadjuvant treatment, the promising activity of SIRT and chemotherapy combination in the unresectable setting, and the prognostic significance of close surgical margins, the aim of this trial is therefore to study this combination treatment in the neoadjuvant setting of resectable ICC.
Detailed Description
The study plans to randomized eligible and consent patients in two balanced parallel groups, the one defined as the experimental arm while the second consisting in the actual standard of care is defined as the control standard arm.
The experimental arm consists in 12 weeks of capecitabine combined with SIRT as neoadjuvant treatment followed by surgery. After SIRT, patients will be assessed at 10 weeks with thoracic-abdominal and pelvic CT scan and liver MRI. If the tumour is still deemed resectable, surgery will be performed at 16 weeks.
In case of discovery of contra-indication to SIRT after inclusion (such as described in the SIRT exclusion criteria section) patients will stop chemotherapy and proceed to surgery within one month. The concerned patients are still included in the study and continue the post-surgery follow-up as expected by the protocol.
In the control arm, patients will proceed to upfront surgery.
The follow - up period begins just after the surgery in both arm, and the patients are evaluated every 3 months for 2 years, then every 6 months for 3 additional years, clinically by an oncologist and radiologically with thoracic-abdominal and pelvic CT scan.
Whether progression occurred, patients will no longer be followed according to the protocol; only vital status continues to be collected until the end of the study (i.e. the last visit of the last patient).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Resectable Intrahepatic Cholangiocarcinoma
Keywords
Selective Internal Radiation Therapy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
62 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Capecitabine combined with SIRT
Arm Type
Experimental
Arm Description
Patients in the experimental arm will be treated with capecitabine combined with Selective Internal Radiotherapy (SIRT) before surgery.
Arm Title
Surgery only
Arm Type
Other
Arm Description
Patients in the control group will receive surgery only.
Intervention Type
Drug
Intervention Name(s)
Capecitabine
Other Intervention Name(s)
L01BC06
Intervention Description
Capecitabine will given at 1250mg/m², 2 times a day with an interval of about 12 hours between two intakes, 2 weeks on, 1 week off, for 4 pre-surgery cycles.
Intervention Type
Device
Intervention Name(s)
Selective Internal Radiotherapy (SIRT)
Intervention Description
During the first week of cycle 2 of capecitabine, patients will receive SIRT using Yttrium-90 glass microspheres. Treatment with Yttrium-90 glass microspheres requires two steps, one or two weeks apart. Both stages are performed under local anesthesia after a short hospitalization : the treatment simulation and therapeutic angiography.
Intervention Type
Procedure
Intervention Name(s)
Surgery
Intervention Description
Surgery will be performed according to local practice.
Primary Outcome Measure Information:
Title
Frequency of subjects with adequate surgical margins
Description
The primary endpoint will be the frequency of subjects with adequate surgical margins, defined as the number of resections AND margin ≥ 5mm.
Time Frame
through study completion, an average of 5 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age > 18 years-old,
ECOG Performance Status <2,
Histologically-proven ICC,
No previous treatment for ICC,
Tumour deemed resectable by a hepatobiliary surgeon, validated by a Surgical Review Board,
Significant risk of close margins, defined as:
Resection margin predicted by the surgeon <1 cm
Tumour >5 cm
Multifocal lesion deemed resectable, validated by a Surgical Review Board
Registration with a social security scheme,
Patient information and signature of informed consent or legal representative.
Non-inclusion Criteria:
Severe fibrosis (F3) ou cirrhosis (F4),
Inadequate haematological, hepatic, renal and coagulation functions:
Haemoglobin ≤ 8,5 g/dl
Neutrophils < 1,5 Giga/L
Platelets < 60 Giga/L
Bilirubin > 34 µmol/L
ASAT/ALAT > 5 x ULN
Creatinine clearance < 30 ml/min (MDRD)
TP et INR > 2,3 ULN
TCA > 1,5 x ULN
Uracil blood level >16 ng/mL,
Respiratory insufficiency,
Comorbidity precluding surgical resection, such as severe heart disease,
Presence of microvacuolar steatosis > 60% or regenerative nodular hyperplasia, for patients for whom a major hepatectomy is planned,
Contraindication to hepatic artery catheterization (vascular abnormalities, bleeding diathesis),
Previous chemotherapy (including for another cancer),
Previous abdominal (supra-mesocolic) radiotherapy (including for another cancer),
Other invasive malignancies,
Patient participate to an interventional study that tests another medical intervention before surgery,
Pregnant woman or likely to be or breastfeeding, or male or female patients of reproductive potential without effective contraception from screening to 30 days after the end of the treatment adjuvant,
Minors, individual deprived of liberty, or under any kind of guardianship,
Patients unable to submit to medical follow-up of the study for social, medical or psychological reasons.
Exclusion Criteria:
Pulmonary shunt with dose >30Gy,
Digestive shunting, non-correctible by interventional radiology,
Absence of fixation of MAA in the tumour.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Marion Trochet
Phone
02 99 25 31 65
Ext
+33
Email
m.trochet@rennes.unicancer.fr
First Name & Middle Initial & Last Name or Official Title & Degree
Valérie Jolaine
Phone
02 99 25 30 36
Ext
+33
Email
v.jolaine@rennes.unicancer.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Julien Edeline, MD
Organizational Affiliation
Centre de Lutte contre le Cancer Eugène Marquis
Official's Role
Principal Investigator
Facility Information:
Facility Name
Centre de Lutte contre le Cancer Eugène Marquis
City
Rennes
State/Province
Bretagne
ZIP/Postal Code
35042
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Julien Edeline, MD PHD
First Name & Middle Initial & Last Name & Degree
Samuel Lesourd, MD
Facility Name
Hôpital Beaujon
City
Clichy
State/Province
Ile-de-France
ZIP/Postal Code
92118
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mohamed Bouattour, MD
First Name & Middle Initial & Last Name & Degree
Clémence Hollande, MD
Facility Name
Hôpital Henri - Mondor
City
Créteil
State/Province
Ile-de-France
ZIP/Postal Code
94000
Country
France
Individual Site Status
Active, not recruiting
Facility Name
Groupe SUD-Haut-Lévêque - Centre Hospitalier Universitaire de Bordeaux
City
Pessac
State/Province
Nouvelle Aquitaine
ZIP/Postal Code
33604
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jean - Frédéric Bland, MD PHD
First Name & Middle Initial & Last Name & Degree
Bérénice Teulières, MD
Facility Name
Centre Hospitalier Universitaire de Montpellier
City
Montpellier
ZIP/Postal Code
34295
Country
France
Individual Site Status
Active, not recruiting
Facility Name
Centre Hospitalier Universitaire de Poitiers
City
Poitiers
ZIP/Postal Code
86021
Country
France
Individual Site Status
Active, not recruiting
Facility Name
Gustave Roussy
City
Villejuif
ZIP/Postal Code
94805
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lambros Tselikas, MD
First Name & Middle Initial & Last Name & Degree
Michel Ducreux, MD
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Selective Internal Radiation Therapy and Capecitabine (Chemotherapy) Treatment for Liver Cancer
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