A Study of GC33 (RO5137382) in Patients With Advanced or Metastatic Hepatocellular Carcinoma

Carcinoma, Hepatocellular Clinical Trial

Official title:

A Randomised, Placebo-controlled, Double-blind, Multicenter Phase II Trial of Intravenous GC33 at 1600 mg Q2W in Previously Treated Patients With Unresectable Advanced or Metastatic Hepatocellular Carcinoma (HCC)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01507168
• Other study ID #: NP27884
• Secondary ID: 2011-003574-84
• Status: Completed
• Phase: Phase 2
• Start date: February 2, 2012
• Est. completion date: August 20, 2015

Study information

• Verified date: April 2020
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This randomized, placebo-controlled, multicenter study will evaluate the efficacy and safety of GC33 (RO5137382) in previously treated patients with unresectable advanced or metastatic hepatocellular carcinoma. Participants will be stratified according to the level of GPC-3 expression in tumors and randomized to receive either GC33 (1600 mg intravenously) or placebo on Days 1 and 8 of Cycle 1 and every 2 weeks thereafter. Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 185
• Est. completion date: August 20, 2015
• Est. primary completion date: August 20, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adult patients, >/= 18 years of age

• Histologically confirmed hepatocellular carcinoma (without fibro-lamellar subtype)

• Prior treatment with at least 1 systemic agent, with documented progressive disease after systemic agent(s), or documented adverse event(s) associated with prior systemic agent(s) that resulted in discontinuance of that (those) agent(s)

• Not a candidate for curative treatments (e.g. resection, transplantation)

• Child-Pugh A (score of 5-6)

• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

• Adequate hematologic, hepatic and renal function

• Ability to provide, for central review, a tumor tissue sample to determine the level of GPC-3 expression by IHC

• Measurable disease by RECIST criteria

Exclusion Criteria:

• Child Pugh B or C

• Known hepatocellular carcinoma with fibro-lamellar histology

• Known brain or leptomeningeal metastases

• Active infectious diseases requiring treatment except for hepatitis B and C

• History of organ allograft including liver transplant

• Anticipated or ongoing administration of anticancer therapies other than those administered in this study

• Anticancer treatment within 2 weeks prior to entering the study

• Patients who have not fully recovered from toxicities associated with previous HCC loco-regional or systemic therapies

• Patients receiving interferon therapy

• Pregnant or lactating women

• Known HIV positivity or AIDS-related illness

• History of significant hypersensitivity to similar agents (monoclonal antibody, protein-included drugs, Chinese hamster ovary products)

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular

Intervention

Drug:
• Placebo
iv Days 1 and 8, and every 2 weeks thereafter
• GC33
1600 mg iv Day 1 and 8, and every 2 weeks thereafter

Locations

Country	Name	City	State
Belgium	Hospital Erasme	Bruxelles
Belgium	UZ Gent	Gent
France	Hotel Dieu; Medecine A	Angers
France	CHU de GRENOBLE; UF de Cancérologie	Grenoble
France	Aphm; Hopital De La Conception	Marseille
France	Hopital de L'Archet; Pole de Reference Hepatite C	Nice
France	Hôpital Saint Antoine; Service Hépathologie	Paris
France	Hopital Purpan;Gastro Enterologie Hepatologie	Toulouse
France	Hôpital d'Adultes; Service hépato-gastro-entérologie	Vandoeuvre-les-nancy
Germany	Charité Uni.-medizin Berlin, Campus Virchow-Klinikum; Med. Klinik m.S. Hepatologie Gastroenterologie	Berlin
Germany	Klinik Johann Wolfgang von Goethe Uni; Zentrum der Inneren Medizin; Medizinische Klinik I	Frankfurt Am Main
Germany	Uni Heidelberg Med. Klinik; Innere Medizin IV	Heidelberg
Germany	Universitätsklinikum Leipzig	Leipzig
Germany	Klinikum rechts der Isar der TU München; Klinikapotheke	Muenchen
Hong Kong	Queen Mary Hospital; Dept of Surgery	Pokfulam
Hong Kong	Prince of Wales Hosp; Dept. Of Clinical Onc	Shatin
Italy	Azienda Ospedaliera G. Rummo; Unità Operativa di Oncologia Medica 1	Benevento	Campania
Italy	Fondazione IRCCS Ospedale Maggiore Policlinico; Gastroenterologia	Milano	Lombardia
Italy	Policlinico Universitario Agostino Gemelli	Roma	Lazio
Japan	National Cancer Center Hospital East	Chiba
Japan	Kanazawa University Hospital	Ishikawa
Japan	Kanagawa Cancer Center	Kanagawa
Japan	Kindai University Hospital	Osaka
Japan	Kyorin University Hospital	Tokyo
Japan	National Cancer Center Hospital	Tokyo
Korea, Republic of	Pusan University Hospital	Busan
Korea, Republic of	National Cancer Center	Gyeonggi-do
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul St Mary's Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
New Zealand	Auckland Hospital; New Zealand Liver Transplant Unit	Auckland
Singapore	National Cancer Centre; Medical Oncology	Singapore
Spain	Hospital Clínic i Provincial; Servicio de Hematología y Oncología	Barcelona
Spain	Hospital Universitari Vall d'Hebron; Servicio de Hepatologia	Barcelona
Spain	Hospital General Universitario Gregorio Marañon	Madrid
Spain	Hospital General Universitario Gregorio Marañon; Servicio de Oncologia	Madrid
Spain	Hospital Universitario 12 de Octubre; Servicio de Oncologia	Madrid
Spain	Hospital Universitario Clínico San Carlos; Servicio de Oncologia	Madrid
Spain	Hospital Universitario Marques de Valdecilla; Servicio de Oncologia	Santander	Cantabria
Spain	Hospital Universitario Miguel Servet; Servicio Hematologia	Zaragoza
Taiwan	Chang Gung Memorial Foundation - Kaohsiung	Kaohsiung
Taiwan	Taichung Veterans Gen Hosp	Taichung
Taiwan	National Cheng Kung Univ Hosp	Tainan
Taiwan	National Taiwan Uni Hospital; Dept of Oncology	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei City
United Kingdom	The Clatterbridge Cancer Ctr NHS Foundation Trust	Bebington
United Kingdom	King'S College Hospital; Haematology	London
United Kingdom	Royal Free Hospital; Dept of Oncology	London
United States	National Cancer Institute; Ctr for Cancer Research	Bethesda	Maryland
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	UCLA Medical Center	Los Angeles	California
United States	Vanderbilt Medical Center	Nashville	Tennessee
United States	Columbia University Medical Center	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Washington Univ School of Med; Barnes-Jewish Hospital; Siteman Cancer Center	Saint Louis	Missouri
United States	Swedish Cancer Inst.	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Belgium,  France,  Germany,  Hong Kong,  Italy,  Japan,  Korea, Republic of,  New Zealand,  Singapore,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival (tumor assessments according to RECIST criteria)		approximately 24 months
Secondary	Overall survival		approximately 32 months
Secondary	Time to progression (TTP): Time from randomization to first documented disease progression		approximately 24 months
Secondary	Disease control rate (DCR): Complete response, partial response or stable disease lasting at least 6 weeks		approximately 24 months
Secondary	Safety: Incidence of adverse events		approximately 24 months
Secondary	Pharmacokinetics: Serum concentrations (Cmax,Cmin)		Multiple sampling pre- and post-dose Days 1 and 8 Cycle 1, Day 1 Cycle 6, pre-dose Day 1 Cycles 2-11
Secondary	GPC-3 expression in tumor tissue (biopsy) by immunohistochemistry (IHC) assay		at screening