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

Purpose

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.

Condition	Intervention	Phase
Intrahepatic Cholangiocarcinoma	Drug: Cisplatin-gemcitabine Device: Radiation: SIRT + chemotherapy (cisplatin-gemcitabine)	Phase 3


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: No masking Primary Purpose: Treatment
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

Resource links provided by NLM:

Genetics Home Reference related topics: cholangiocarcinoma

Drug Information available for: Cisplatin Gemcitabine Gemcitabine hydrochloride

Genetic and Rare Diseases Information Center resources: Bile Duct Cancer Intrahepatic Cholangiocarcinoma

U.S. FDA Resources

Further study details as provided by Sirtex Medical:

Primary Outcome Measures:

Survival at 18 months [ Time Frame: 18 months following the date of randomization. ]
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) [ 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.. ]
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. ]
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. ]
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. ]
Overall Survival [ Time Frame: From date of randomization until the date of death from any cause, assessed up to 36 months. ]
Liver surgical resection and ablation rate [ Time Frame: 18 months following the date of randomization. ]
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) [ Time Frame: Informed consent until 28 days post last dose of protocol chemotherapy. ]
Adverse events as assessed by CTCAE v. 4.0.


Estimated Enrollment:	180
Actual Study Start Date:	January 2017
Estimated Study Completion Date:	December 2019
Estimated Primary Completion Date:	December 2019 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: 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.	Drug: Cisplatin-gemcitabine Systemic chemotherapy Other Name: CIS-GEM
Experimental: 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.	Drug: Cisplatin-gemcitabine Systemic chemotherapy Other Name: CIS-GEM Device: Radiation: SIRT + chemotherapy (cisplatin-gemcitabine) SIR-Spheres microspheres followed by systemic chemotherapy

Arms

Assigned Interventions

Active Comparator: 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.

Drug: Cisplatin-gemcitabine

Systemic chemotherapy

Other Name: CIS-GEM

Experimental: 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.

Drug: Cisplatin-gemcitabine

Systemic chemotherapy

Other Name: CIS-GEM

Device: Radiation: SIRT + chemotherapy (cisplatin-gemcitabine)

SIR-Spheres microspheres followed by systemic chemotherapy

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.

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02807181

Contacts


Contact: Florence Chow	49 228 1840 713	fchow@sirtex-europe.com

Show 35 Study Locations

Sponsors and Collaborators

Sirtex Medical

Investigators


Principal Investigator:	Jordi Bruix, MD	Head of the Hepatic Oncology Unit, Hospital Clinic
Principal Investigator:	Harpreet Wasan, MD	Imperial College Healthcare Hammersmith Hospital

More Information


Responsible Party:	Sirtex Medical
ClinicalTrials.gov Identifier:	NCT02807181 History of Changes
Other Study ID Numbers:	STX0115
Study First Received:	May 13, 2016
Last Updated:	July 13, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

Additional relevant MeSH terms:


Cholangiocarcinoma Adenocarcinoma Carcinoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Gemcitabine Cisplatin Antineoplastic Agents	Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Antiviral Agents Anti-Infective Agents Enzyme Inhibitors Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 25, 2017

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