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

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.

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.

Study Overview

• Status: Completed
• Conditions: Cholangiocarcinoma
• Intervention / Treatment: Radiation: Therasphere® in association with Gemcitabine and Cisplatin

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Clichy, France, 92118
    • Hôpital Beaujon - Service de Chirurgie
  • Créteil, France, 94010
    • Hopital Henri Mondor
  • Montpellier, France, 34295
    • Hôpital Saint-Eloi
  • Nancy, France, 54000
    • CHU Nancy - Hôpital Brabois
  • Nantes, France, 44093
    • CHU- Hotel Dieu
  • Poitiers, France
    • CHU Poitiers
  • Rennes, France, 35042
    • Centre Eugène Marquis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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 Names: 90-Yttrium theraspheres

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiological response rate to the treatment with the association of chemotherapy and radioembolization	Evaluation according RECIST 1.1 criteria. Rate will be reassessed every 8 weeks	3 months after radioembolization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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	Up to 24 months
Tumor markers changes (CA19.9, CEA and AFP)	Markers will be analysed every 8 weeks during treatment period and if applicable every 12 weeks after surgery	Up to 24 months
Radiological response rate by the CHOI criteria	every 8 weeks and every 12 weeks after surgery if applicable	Up to 24 months
Change in metabolic activity measured by TEP		Change from baseline in metabolic activity 15 and 24 weeks after last treatment by microspheres
Changes of liver volume	Every 8 weeks during treatment and every 12 weeks after surgery if applicable	Up to 24 months
Tumoral and non-tumoral dosimetric assessment of the liver	Data obtained from SPECT/CT performed at each hepatic scintigraphy	Up to 6 months

Collaborators and Investigators

• Sponsor: Center Eugene Marquis
• Investigators: Principal Investigator: Eveline Boucher, MD, Centre Eugène Marquis

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2013
• Primary Completion (Actual): December 1, 2016
• Study Completion (Actual): November 1, 2017

Study Registration Dates

• First Submitted: July 17, 2013
• First Submitted That Met QC Criteria: July 29, 2013
• First Posted (Estimate): July 30, 2013

Study Record Updates

• Last Update Posted (Actual): May 11, 2018
• Last Update Submitted That Met QC Criteria: May 7, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: Intra-hepatic Cholangiocarcinoma treatment
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Cholangiocarcinoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gemcitabine
• Other Study ID Numbers: 2012-EB-CHOL-Th; 2012-001213-16 (EudraCT Number); A121007-71 (Registry Identifier: French National Health)