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

NCT02807181 | Terminated Phase 2 Results DMC FDA Device

• 1 other identifier: STX0115
• Study Type: interventional
• Target: 89
• Locations: 8 countries
• Sites: 23

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.

Conditions

Intrahepatic Cholangiocarcinoma

Outcome Measures

Primary Outcomes (1)

• Survival at 18 Months

  Survival at 18 months is defined as the proportion of patients still alive 18 months from the date of randomization. The outcome was analyzed but the clinical database is not deemed to be reliable.

  18 months following the date of randomization.

Secondary Outcomes (7)

• Liver-specific Progression Free Survival (PFS)

  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

  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

  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

  From the date of first treatment until progression at any site, assessed up to 36 months.

• Overall Survival

  From date of randomization until the date of death from any cause, assessed up to 36 months.

Study Arms (2)

Chemotherapy (Cisplatin-Gemcitabine)

ACTIVE COMPARATOR

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

Radiation: SIRT + chemotherapy (Cisplatin-Gemcitabine)

EXPERIMENTAL

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

Interventions

Cisplatin-gemcitabine DRUG

Systemic chemotherapy

Also known as: CIS-GEM

Chemotherapy (Cisplatin-Gemcitabine); Radiation: SIRT + chemotherapy (Cisplatin-Gemcitabine)

Radiation: SIRT + chemotherapy (cisplatin-gemcitabine) DEVICE

SIR-Spheres microspheres followed by systemic chemotherapy

Radiation: SIRT + chemotherapy (Cisplatin-Gemcitabine)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sirtex Medical: lead

Study Sites (23)

Providence Health Care

Spokane, Washington, 99204, United States

Location

Macquarie University Hospital

North Ryde, New South Wales, 2109, Australia

Location

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

Location

Cliniques Universitaires Saint-Luc

Brussels, 1200, Belgium

Location

Hopital Beaujon

Clichy, 92110, France

Location

CHU Dijon

Dijon, 21079, France

Location

CHU de Grenoble

Grenoble, 38043, France

Location

CHU Lyon - Hospital de la Croix-Rousse

Lyon, 69317, France

Location

Institut Paoli Calmettes

Marseille, 13009, France

Location

CHU Montpellier

Montpellier, 34295, France

Location

CHU Nice - Hopital l'Archet 2

Nice, 06202, France

Location

Hopital Haut-Leveque

Pessac, 33604, France

Location

CHU de Poitiers

Poitiers, 86021, France

Location

Centre Eugene Marquis Hospital de Jour

Rennes, 35042, France

Location

Hopital Paul Brousse

Villejuif, 94800, France

Location

U.O. Oncologia Medica 2 Universitaria

Pisa, 56126, Italy

Location

AMC Academic Medical Center

Amsterdam, 1105, Netherlands

Location

Hospital Clinic Barcelona

Barcelona, 08036, Spain

Location

Clinica Universitaria de Navarra

Pamplona, 31008, Spain

Location

Hammersmith Hospital Imperial College Healthcare NHS Trust

London, W12 0HS, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

The Clatterbridge Cancer Centre NHS Foundation Trust

Metropolitan Borough of Wirral, CH63 4JY, United Kingdom

Location

Southampton General Hospital

Southampton, S016 6YD, United Kingdom

Location

MeSH Terms

Conditions

Cholangiocarcinoma

Interventions

Drug Therapy

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Therapeutics

Limitations and Caveats

SIRCCA enrollment from February 2017 (180 planned) was slow and thus enrollment terminated early in October 2019 (89 treated). Follow-up until 29 April 2021 was to ensure ≥18 months of data although the primary endpoint was underpowered. An audit to the clinical database detected issues leading to a low level of confidence in the trustworthiness of the collected data. Pharmacovigilance case reconciliation was thus also confounded. The results posted cannot be relied upon as accurate.

Results Point of Contact

• Title: Director, Clinical Research Operations
• Organization: Sirtex

info-us@sirtex.com

+1-888-474-7839

Study Officials

• Jordi Bruix, MD

  Head of the Hepatic Oncology Unit, Hospital Clinic

  PRINCIPAL INVESTIGATOR

• Harpreet Wasan, MD

  Imperial College Healthcare Hammersmith Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 13, 2016
• First Posted: June 21, 2016
• Study Start: February 14, 2017
• Primary Completion: April 29, 2021
• Study Completion: April 29, 2021
• Last Updated: May 9, 2025
• Results First Posted: May 9, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

FR (11); AU (2); GB (4); NL (1); ES (2); BE (1); US (1); IT (1)