Clinical trial NCT01507168: A Study of GC33 (RO5137382) in Patients With Advanced or Metastatic Hepatocellular Carcinoma
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Carcinoma, Hepatocellular
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2012-01-10
Enrollment: 185
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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)

Primary outcomes:
measure: Progression-free survival (tumor assessments according to RECIST criteria)
timeFrame: approximately 24 months
Secondary outcomes:
measure: Overall survival
timeFrame: approximately 32 months
measure: Time to progression (TTP): Time from randomization to first documented disease progression
timeFrame: approximately 24 months
measure: Disease control rate (DCR): Complete response, partial response or stable disease lasting at least 6 weeks
timeFrame: approximately 24 months
measure: Safety: Incidence of adverse events
timeFrame: approximately 24 months
measure: Pharmacokinetics: Serum concentrations (Cmax,Cmin)
timeFrame: Multiple sampling pre- and post-dose Days 1 and 8 Cycle 1, Day 1 Cycle 6, pre-dose Day 1 Cycles 2-11
measure: GPC-3 expression in tumor tissue (biopsy) by immunohistochemistry (IHC) assay
timeFrame: at screening
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA Medical Center
state: California
city: Bethesda
country: United States
facility: National Cancer Institute; Ctr for Cancer Research
state: Maryland
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Saint Louis
country: United States
facility: Washington Univ School of Med; Barnes-Jewish Hospital; Siteman Cancer Center
state: Missouri
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Nashville
country: United States
facility: Vanderbilt Medical Center
state: Tennessee
city: Seattle
country: United States
facility: Swedish Cancer Inst.
state: Washington
city: Bruxelles
country: Belgium
facility: Hospital Erasme
city: Gent
country: Belgium
facility: UZ Gent
city: Angers
country: France
facility: Hotel Dieu; Medecine A
city: Grenoble
country: France
facility: CHU de GRENOBLE; UF de Cancérologie
city: Marseille
country: France
facility: Aphm; Hopital De La Conception
city: Nice
country: France
facility: Hopital de L'Archet; Pole de Reference Hepatite C
city: Paris
country: France
facility: Hôpital Saint Antoine; Service Hépathologie
city: Toulouse
country: France
facility: Hopital Purpan;Gastro Enterologie Hepatologie
city: Vandoeuvre-les-nancy
country: France
facility: Hôpital d'Adultes; Service hépato-gastro-entérologie
city: Berlin
country: Germany
facility: Charité Uni.-medizin Berlin, Campus Virchow-Klinikum; Med. Klinik m.S. Hepatologie Gastroenterologie
city: Frankfurt Am Main
country: Germany
facility: Klinik Johann Wolfgang von Goethe Uni; Zentrum der Inneren Medizin; Medizinische Klinik I
city: Heidelberg
country: Germany
facility: Uni Heidelberg Med. Klinik; Innere Medizin IV
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig
city: Muenchen
country: Germany
facility: Klinikum rechts der Isar der TU München; Klinikapotheke
city: Pokfulam
country: Hong Kong
facility: Queen Mary Hospital; Dept of Surgery
city: Shatin
country: Hong Kong
facility: Prince of Wales Hosp; Dept. Of Clinical Onc
city: Benevento
country: Italy
facility: Azienda Ospedaliera G. Rummo; Unità Operativa di Oncologia Medica 1
state: Campania
city: Roma
country: Italy
facility: Policlinico Universitario Agostino Gemelli
state: Lazio
city: Milano
country: Italy
facility: Fondazione IRCCS Ospedale Maggiore Policlinico; Gastroenterologia
state: Lombardia
city: Chiba
country: Japan
facility: National Cancer Center Hospital East
city: Ishikawa
country: Japan
facility: Kanazawa University Hospital
city: Kanagawa
country: Japan
facility: Kanagawa Cancer Center
city: Osaka
country: Japan
facility: Kindai University Hospital
city: Tokyo
country: Japan
facility: National Cancer Center Hospital
city: Tokyo
country: Japan
facility: Kyorin University Hospital
city: Busan
country: Korea, Republic of
facility: Pusan University Hospital
city: Gyeonggi-do
country: Korea, Republic of
facility: National Cancer Center
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul St Mary's Hospital
city: Auckland
country: New Zealand
facility: Auckland Hospital; New Zealand Liver Transplant Unit
city: Singapore
country: Singapore
facility: National Cancer Centre; Medical Oncology
city: Santander
country: Spain
facility: Hospital Universitario Marques de Valdecilla; Servicio de Oncologia
state: Cantabria
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron; Servicio de Hepatologia
city: Barcelona
country: Spain
facility: Hospital Clínic i Provincial; Servicio de Hematología y Oncología
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon; Servicio de Oncologia
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
city: Madrid
country: Spain
facility: Hospital Universitario Clínico San Carlos; Servicio de Oncologia
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre; Servicio de Oncologia
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet; Servicio Hematologia
city: Kaohsiung
country: Taiwan
facility: Chang Gung Memorial Foundation - Kaohsiung
city: Taichung
country: Taiwan
facility: Taichung Veterans Gen Hosp
city: Tainan
country: Taiwan
facility: National Cheng Kung Univ Hosp
city: Taipei City
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taipei
country: Taiwan
facility: National Taiwan Uni Hospital; Dept of Oncology
city: Bebington
country: United Kingdom
facility: The Clatterbridge Cancer Ctr NHS Foundation Trust
city: London
country: United Kingdom
facility: Royal Free Hospital; Dept of Oncology
city: London
country: United Kingdom
facility: King'S College Hospital; Haematology
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Pradier MF, Reis B, Jukofsky L, Milletti F, Ohtomo T, Perez-Cruz F, Puig O. Case-control Indian buffet process identifies biomarkers of response to Codrituzumab. BMC Cancer. 2019 Mar 28;19(1):278. doi: 10.1186/s12885-019-5472-0.
citation: Abou-Alfa GK, Puig O, Daniele B, Kudo M, Merle P, Park JW, Ross P, Peron JM, Ebert O, Chan S, Poon TP, Colombo M, Okusaka T, Ryoo BY, Minguez B, Tanaka T, Ohtomo T, Ukrainskyj S, Boisserie F, Rutman O, Chen YC, Xu C, Shochat E, Jukofsky L, Reis B, Chen G, Di Laurenzio L, Lee R, Yen CJ. Randomized phase II placebo controlled study of codrituzumab in previously treated patients with advanced hepatocellular carcinoma. J Hepatol. 2016 Aug;65(2):289-95. doi: 10.1016/j.jhep.2016.04.004. Epub 2016 Apr 13.