Efficacy Study of Intra-hepatic Administration of Therasphere® in Association With Intravenous Chemotherapy to Treat Cholangiocarcinoma (MispheC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01912053
Recruitment Status : Completed
First Posted : July 30, 2013
Last Update Posted : May 11, 2018
Information provided by (Responsible Party):
Center Eugene Marquis

Brief Summary:
The purpose of this study is to assess efficacy and tolerance of intra-hepatic administration of Yttrium 90-labelled microsphere (Theraspheres®, Nordion) in association with intravenous chemotherapy with Gemcitabin and Cisplatin for the treatment of intra-hepatic cholangiocarcinoma.

Condition or disease Intervention/treatment Phase
Cholangiocarcinoma Radiation: Therasphere® in association with Gemcitabine and Cisplatin Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 41 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label, Multicenter, Phase II Trial, to Evaluate the Efficacy of Intra-hepatic Administration of Yttrium 90-labelled Microspheres (Therasphere®, Nordion) in Association With Intravenous Chemotherapy With Gemcitabine and Cisplatin for the Treatment of Intra-hepatic Cholangiocarcinoma, First Line.
Actual Study Start Date : September 2013
Actual Primary Completion Date : December 2016
Actual Study Completion Date : November 2017

Arm Intervention/treatment
Experimental: Therasphere®
Therasphere® in association with Gemcitabine and Cisplatin
Radiation: Therasphere® in association with Gemcitabine and Cisplatin
Therasphere® is a radioelement
Other Name: 90-Yttrium theraspheres

Primary Outcome Measures :
  1. Radiological response rate to the treatment with the association of chemotherapy and radioembolization [ Time Frame: 3 months after radioembolization ]
    Evaluation according RECIST 1.1 criteria. Rate will be reassessed every 8 weeks

Secondary Outcome Measures :
  1. Tolerance of intra-hepatic administration of Yttrium 90-labelled microspheres in association with intravenous chemotherapy with Gemcitabine and Cisplatin assessed according NCI/CTC AE version 4. [ Time Frame: Up to 24 months ]
    Grade 3-4 toxicity appearance.Time between 1st treatment administration and date of 1st appearance of a grade 3-4 toxicity or date of last toxicities assessment in case no grade 3-4 toxicity

  2. Tumor markers changes (CA19.9, CEA and AFP) [ Time Frame: Up to 24 months ]
    Markers will be analysed every 8 weeks during treatment period and if applicable every 12 weeks after surgery

  3. Radiological response rate by the CHOI criteria [ Time Frame: Up to 24 months ]
    every 8 weeks and every 12 weeks after surgery if applicable

  4. Change in metabolic activity measured by TEP [ Time Frame: Change from baseline in metabolic activity 15 and 24 weeks after last treatment by microspheres ]
  5. Changes of liver volume [ Time Frame: Up to 24 months ]
    Every 8 weeks during treatment and every 12 weeks after surgery if applicable

  6. Tumoral and non-tumoral dosimetric assessment of the liver [ Time Frame: Up to 6 months ]
    Data obtained from SPECT/CT performed at each hepatic scintigraphy

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

Inclusion Criteria:

  1. Histologically confirmed intra-hepatic cholangiocarcinoma.
  2. Measurable target of at least 2 cm diameter.
  3. Healthy liver or cirrhosis CHILD < B8.
  4. WHO-PS: 0-1.
  5. Age ≥ 18 years.
  6. Non-Metastatic disease in extra-hepatic (are permitted: local lymph nodes < 3 cm, less than 5 lung nodes < 11 mm).
  7. Creatinine clearance (calculated with Cockcroft and Gault formula) ≥ 55 ml/min, polymorphonuclear neutrophils ≥ 1500 G/L, platelets ≥ 80 G/L, prothrombin ≥ 40% (INR ≤ 2.3), serum albumin ≥ 28 g/l, serum bilirubin ≤ 3 x LSN.
  8. Pregnancy test: negative for women of childbearing potential.
  9. Reliable contraception for a childbearing couple, men and woman must have an reliable contraception during the treatment and until 6 months following the end of the treatment by chemotherapy
  10. Signed informed consent form.
  11. Patient with national health insurance.

Exclusion Criteria:

  1. Pancreas cancer or duodenum cancer invading the bile duct or ampullary cancer. Cholangiocarcinoma of the bile ducts: hilar, main duct, gallbladder.
  2. Extra-hepatic metastasis (including local lymph nodes measuring > 30 mm).
  3. Primary sclerosing cholangitis.
  4. History of chemoembolization or radioembolization.
  5. Cirrhose CHILD > B7
  6. Portal vein trunk tumoral thrombosis
  7. History of hepato-biliary neo adjuvant or palliative chemotherapy and/or radiotherapy.
  8. Contra indication of Gemcitabine and/or Cisplatin.
  9. Other invasive active cancer, excepting in situ cervical cancer and basocellular or spino cellular skin cancer treated adequately. Any history of cancer not considered as completely cured for at least one year.
  10. Technical failure of the diagnostic arteriography.
  11. Extra hepatic uptake on the pre-therapeutic scintigraphy not manageable with an arteriography.
  12. Dosimetry study predicting lung exposure > 30 Gy.
  13. Any unstable medical history (diabetes, hypertension …).
  14. History of organ transplant.
  15. Symptomatic grade 1 angina pectoris or grade ≥ 2 angina pectoris.
  16. An evolutive neuropathy.
  17. Patient who already has been involved in a clinical trial with drug intake, whether this drug was experimental or not, within 30 days before.
  18. Pregnant patient or patient with breastfeeding.
  19. Patient under administrative supervision.
  20. Regular follow-up impossible for various reasons (psychological, familial, economical, and social).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01912053

Hôpital Beaujon - Service de Chirurgie
Clichy, France, 92118
Hôpital Henri Mondor
Créteil, France, 94010
Hôpital saint-Eloi
Montpellier, France, 34295
CHU Nancy - Hôpital Brabois
Nancy, France, 54000
CHU- Hotel Dieu
Nantes, France, 44093
CHU Poitiers
Poitiers, France
Centre Eugene Marquis
Rennes, France, 35042
Sponsors and Collaborators
Center Eugene Marquis
Principal Investigator: Eveline Boucher, MD Centre Eugene Marquis

Responsible Party: Center Eugene Marquis Identifier: NCT01912053     History of Changes
Other Study ID Numbers: 2012-EB-CHOL-Th
2012-001213-16 ( EudraCT Number )
A121007-71 ( Registry Identifier: French National Health )
First Posted: July 30, 2013    Key Record Dates
Last Update Posted: May 11, 2018
Last Verified: January 2018

Keywords provided by Center Eugene Marquis:
Intra-hepatic Cholangiocarcinoma treatment

Additional relevant MeSH terms:
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Antineoplastic Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs