Phase III Study of Rindopepimut/GM-CSF in Patients With Newly Diagnosed Glioblastoma

Glioblastoma Clinical Trial

— ACT IV  

Official title:

An International, Randomized, Double-Blind, Controlled Study of Rindopepimut/GM-CSF With Adjuvant Temozolomide in Patients With Newly Diagnosed, Surgically Resected, EGFRvIII-positive Glioblastoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01480479
• Other study ID #: CDX110-04
• Status: Completed
• Phase: Phase 3
• First received: November 21, 2011
• Last updated: January 11, 2018
• Start date: November 2011
• Est. completion date: November 2016

Study information

• Verified date: April 2017
• Source: Celldex Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This 2-arm, randomized, phase III study will investigate the efficacy and safety of the addition of rindopepimut (an experimental cancer vaccine that may act to promote anti-cancer effects in patients who have tumors that express the EGFRvIII protein) to the current standard of care (temozolomide) in patients with recently diagnosed glioblastoma, a type of brain cancer.

All patients will be administered temozolomide, the standard treatment for glioblastoma. Half the patients will be randomly assigned to receive rindopepimut and half the patients will be randomly assigned to receive a control called keyhole limpet hemocyanin.

Patients will be treated in a blinded fashion (neither the patient or the doctor will know which arm of the study the patient is on). Patients will be treated until disease progression or intolerance to therapy and all patients will be followed for survival.

Description:

The purpose of this research study is to find out whether adding an experimental vaccine called rindopepimut (also known as CDX-110) to the commonly used chemotherapy drug temozolomide can help improve the life expectancy of patients with newly diagnosed, resected EGFRvIII positive glioblastoma.

The duration of participation in this study may be up to 5 years. After you are screened and enrolled in the study, you will be administered temozolomide and either rindopepimut/GM-CSF or KLH until either disease progression or intolerance to the medications. If your tumor progresses while on this study, your doctor may treat you with other therapies that are not part of the study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 745
• Est. completion date: November 2016
• Est. primary completion date: November 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria-

Among other criteria, patients must meet the following conditions to be eligible for the study:

1. Adult patients, = 18 years old

2. Newly diagnosed glioblastoma

3. Attempted surgical resection followed by conventional chemoradiation

4. Documented EGFRvIII positive tumor status by a Sponsor designated laboratory

5. No evidence of progressive disease from the post-operative period to the post-chemoradiation period

6. Candidate for, and agrees to receive, adjuvant (maintenance) temozolomide therapy

7. Systemic corticosteroid therapy at =2 mg of dexamethasone or equivalent per day for at least 3 days prior to randomization

8. WHO-ECOG Performance Status = 2

9. Patients of childbearing/reproductive potential will be instructed to use birth control as defined by your doctor.

Exclusion Criteria-

Among other criteria, patients who meet the following conditions are NOT eligible for the study:

1. Stereotactic biopsy only (without further surgical resection)

2. Presence of diffuse leptomeningeal disease, gliomatosis cerebri, or infratentorial disease.

3. History, presence, or suspicion of metastatic disease

4. Patients who have received any additional treatment for glioblastoma, aside from surgical resection and chemoradiation with temozolomide

5. Active systemic infection requiring treatment

6. History of any malignancy (other than glioblastoma) during the last three years except non-melanoma skin cancer, in situ cervical cancer, treated superficial bladder cancer, cured, early-stage prostate cancer in a patient with PSA level less than ULN,or other carcinoma in situ that has been adequately treated and cured.

7. Planned major surgery

8. Evidence of current drug or alcohol abuse

9. Known allergy or hypersensitivity to keyhole limpet hemocyanin (KLH), GM-CSF (sargramostim; LEUKINE®), polysorbate 80 or yeast derived products, or a history of anaphylactic reactions to shellfish proteins

10. Severe acute or chronic medical or psychiatric condition or laboratory abnormality that could increase the risk associated with participating in a clinical trial

11. Women who are pregnant or lactating

Related Conditions & MeSH terms

• Giant Cell Glioblastoma
• Glioblastoma
• Glioblastoma With Oligodendroglial Component
• Gliosarcoma
• Small Cell Glioblastoma

Intervention

Drug:
• Rindopepimut (CDX-110) with GM-CSF
Two intradermal injections two weeks apart, followed by monthly injections until tumor progression or intolerance. Each dose will be 0.8 mL containing approximately 500 mcg CDX-110 and 150 mcg GM CSF.
• Temozolomide
150 to 200 mg/m2 for 5 days during each 28-day cycle for a minimum of six cycles or a maximum of 12 cycles, or until intolerance or progression.
• KLH
Two intradermal injections two weeks apart, followed by monthly injections until tumor progression or intolerance. Each dose will be 0.8mL containing approximately 100mcg of KLH.

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Monash Medical Centre	Clayton	Victoria
Australia	Austin Health	Heidelberg	Victoria
Australia	Royal Brisbane and Women's Hospital	Herston	Queensland
Australia	Royal Hobart Hospital	Hobart	Tasmania
Australia	Launceston General Hospital	Launceston	Tasmania
Australia	Liverpool Hospital	Liverpool
Australia	Sir Charles Gairdner Hospital	Nedlands	Western Australia
Australia	Calvary North Adelaide Hospital	North Adelaide	South Australia
Australia	Prince of Wales Hospital	Randwick	New South Wales
Australia	Epworth Healthcare	Richmond	Victoria
Australia	Mater Adult Hospital, Mater Misericordiae Health Services Brisbane Limited	South Brisbane	Queensland
Australia	Royal North Shore Hospital	St Leonards	New South Wales
Australia	The Crown Princess Mary Cancer Centre, Westmead Hospital	Westmead	New South Wales
Austria	Medical University Innsbruck, Dept of Neurology, Anichstrabe 35	Innsbruck
Austria	Medizinische Universität Wien, Innere Medizin I, Onkologie	Vienna
Belgium	ZNA Middelheim	Antwerpen
Belgium	Universitair Ziekenhuis Antwerpen	Edegem	Antwerp
Belgium	Ghent University Hospital	Ghent
Brazil	Centro de Pesquisas Clinicas da Fundação Dr Amaral Carvalho	Jaú	São Paulo
Brazil	Hospital Mae de Deus-Centro de Pesquisa em Oncologia Clinica	Porto Alegre	Rio Grande Do Sul
Brazil	Instituto Nacional do Cancer (INCA)	Rio de Janeiro
Brazil	Fundação Faculdade Regional de Medicina de de São José do Rio Preto - Hospital de Base	São José do Rio Preto	São Paulo
Brazil	Hospital Albert Einstein	Sao Paulo
Brazil	Hospital A C Camargo	São Paulo
Brazil	Instituto do Câncer do Estado de São Paulo - ICESP	São Paulo
Brazil	Real e Benemerita Associação Portuguesa de Beneficiência/ Hospital São José	São Paulo
Canada	Foothills Hospital Medical Centre	Calgary	Alberta
Canada	QEII Health Sciences Centre	Halifax	Nova Scotia
Canada	Juravinski Cancer Centre	Hamilton	Ontario
Canada	London Regional Cancer Program, London Health Sciences Centre	London	Ontario
Canada	Centre Hospitalier de l'Universite de Montreal (CHUM) - Hopital Notre-Dame	Montreal	Quebec
Canada	Montreal Neurological Institute and Hospital	Montreal	Quebec
Canada	Ottawa Hospital, Regional Cancer Centre	Ottawa	Ontario
Canada	CHUQ L'Hotel Dieu de Qujebec	Quebec
Canada	CHUS Hôpital Fleurimont	Shenbrooke	Quebec
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario
Canada	British Columbia Cancer Agency, Vancouver Clinic	Vancouver	British Columbia
Canada	BC Cancer Agency - Vancouver Island Centre	Victoria	British Columbia
Canada	University of Manitoba-Cancer Care Manitoba	Winnipeg	Manitoba
Colombia	Fundacion Santa Fe	Bogota	Bogota D.C
Czechia	Hospital Ceske Budejovice	Ceske Budejovice
Czechia	Hospital Na Homolce	Prague
Czechia	Umiversity Hospital (Fakultni Nemocnice)	Prague
Czechia	Multiscan s.r.o.	Praha 5
Czechia	Masaryk´s Hospital Usti nad Labem	Usti nad Labem
France	Institut de Cancerologie de I'Quest-Paul Papin	Angers
France	Institute Bergonie	Bordeaux
France	Centre Leon Berard de Lyon	Lyon
France	ICM Val d'Aurel Montpellier	Montpellier
France	Institut de Cancerologie de L'Quest-Center Rane Gauducheau	Nantes
France	Service de Neurologie-GH	Paris
France	Centre Eugene Marquis	Rennes
France	Institut de Cancerologie de l'ouest-Center Rene Gauducheau	St Herblain
France	Institut Gustave Roussy	Villejuif
Germany	Strahlenklinik Universitatsklinikum Erlangen	Erlangen
Germany	Dr. Senchkenbergisches Institut fur Neuroonkologie	Frankfurt
Germany	University Hospital Hamburg Kopf und Neurozentrum	Hamburg
Germany	Universitaetsklinikum Heidelberg, Neurologische Klinik, IM Neuenheimer Feld 672	Heidelberg
Germany	University Medical Centre	Kiel
Germany	Universitaetsklinikum Muenster	Muenster
Germany	LMU Munich	Munich
Germany	Klinik und Poliklinik fur Neurologie der Universitat Regensburg	Regensburg	Bavaria
Greece	NNA	Athens	Attiki
Greece	"HYGEIA" Hospital	Marousi	District Of Attica
Hungary	Országos Onkológiai Intézet Sugárterápiás Osztály	Budapest
Hungary	Debreceni Egyetem Orvos- és Egészségtudományi Centrum Onkológiai Intézet	Debrecen
Hungary	Borsod-Abaúj-Zemplén Megyei Kórház és Egyetemi Oktató Kórház, Sugárterápiás Osztály	Miskolc
Hungary	Pécsi Tudományegyetem Általános Orvostudományi Kar	Pécs
Hungary	Szegedi Tudományegyetem Onkoterápiás Klinika	Szeged
Hungary	Vas Megyei Markusovszky Lajos Általános Rehabilitációs és Gyógyfürdo Kórház, Egyetemi Oktatókórház Nonprofit Zrt	Szombathely
India	Kokilaben Dhirubhai Ambani Hospital and Medical Research Institute	Andheri-West	Mumbai
India	Marathwada Regional Cancer Centre and Research Institute - Government	Aurangabad	Maharashtra
India	HCG - Bangalore Institute of Oncology, Bangalore	Bengaluru	Karnataka
India	Dr. Rai Memorial Medical Centre, Chennai	Chennai	Tamil Nadu
India	HCG Shanti Mukand Hospital - Curie Cancer Centre, Delhi	Delhi
India	Sahyadri Hospitals Limited	Erandauame	Pune
India	Indraprastha Apollo Hospital, New Delhi	Jasola Viha	New Delhi
India	Amrita Institute of Medical Sciences and Research Centre, Kochi	Kochi	Kerala
India	Tata Memorial Hospital , Mumbai	Parel	Mumbai
India	Sree Chitra Tirunal Institute for Medical Sciences & Technology, Thiruvananthapuram	Thiruvananthapuram	Kerala
India	City Cancer Centre, Vijayawada	Vijayawada	Andhra Pradesh
Israel	Soroka University M.C.	Beer-Sheva
Israel	Rambam Health Care Campus	Haifa
Israel	Hadassah Medical Center	Jerusalem
Israel	SHEBA Medical Center	Tel Hashomer
Israel	Tel-Aviv Sourasky Medical Center	Tel-Aviv
Italy	UO Oncologie Medica Dipartimento Oncologico	Bologna
Italy	Fondazione IRCCS Instituto Neurologico Carlo Besta	Milano
Italy	Sacred Heart Catholic University	Rome
Italy	Universita e AO Citta delia Scienza, Universita Di Torino	Torino
Mexico	Ensayos Clínicos y Medicina de Alta Especialidad, S.C.	Culiacán	Sinaloa
Mexico	Servicios Medicos de Investigacion Clinica Sc	Durango
Mexico	Hospital Civil de Guadalajara "Fray Antonio Alcalde"	Guadalajara	Jalisco
Mexico	Grupo Médico Camino S.C.	Mexico	D.F
Mexico	Hospital Central "Ignacio Morones Prieto"	San Luis Potosí
Netherlands	VUMC	Amsterdam
Netherlands	Radboud University Nijmegen Medical Center	Nijmegen
Netherlands	Medisch Centrum Haaglanden	The Hague	Zuid Holland
New Zealand	Christchurch Hospital	Christchurch Central	Christchurch
New Zealand	Waikato Hospital, Regional Cancer Center	Hamilton	Waikato Distric
New Zealand	Waikato Hospital, Regional Cancer Centre	Hamilton	Waikato District
New Zealand	Palmerston North Hospital	Roslyn	Palmerston North
Peru	Hospital Almanzor Aguinaga Asenjo	Chiclayo
Peru	Clinica Anglo Americana	Lima
Peru	Clinica Ricardo Palma	Lima
Peru	Instituto Oncologico Miraflores	Lima
Peru	Oncosalud	Lima
Spain	Hospital Clinic	Barcelona
Spain	ICO Badalona-Hospital Germans Trias i Pujol	Barcelonia
Spain	Dra. Sonia Del Barco Berron, ICO Girona Avda,	Franca	Girona
Spain	Institut Catala d Oncologia	LaHospitalet De Lubregat	Catalonia
Spain	Hospital 12 de Octubre	Madrid
Switzerland	Kantonsspital Aarau Medizinische Onkologie Tellstrasse	Aarau	AG
Switzerland	Oncology Institute of Southern Switzerland (IOSI)	Bellinzona
Switzerland	Inselspital, Universitatsspital Bern, Universitatsklinik fur Medizinische Onkologie, Freiburgstrasse	Bern
Switzerland	Hopitaux Universitaires de Geneve-HUG-Centre d'Oncologie	Geneva
Switzerland	CHUV, Centre Hospitalier Universitaire Vaudois	Lausanne	VD
Switzerland	Brain Tumor Center, University Hospital Zurich	Zurich
Taiwan	Kaohsiung Chang Gung Memorial Hospital	Kaohsiung
Taiwan	Chang Gung Memorial Hospital Linkou Branch	Taichung
Taiwan	Taichung Veterans General Hospital	Taichung
Taiwan	National Cheng Kung University Hospital	Tainan City	Bei District
Taiwan	Chi Mei Medical Center	Tainan City - Yongkang District
Taiwan	Tri-Service General Hospital	Taipei city - Neihu District
Thailand	Maharaj Nakorn Chiang Mai Hospital	Amphoe Muang	Chiang Mai
Thailand	Siriraj Hospital	Bangkoknoi	Bangkok
Thailand	Songkhlanagarind Hospital	Hat Yai	Songkla
Thailand	King Chulalongkorn Memorial Hospital	Patumwan	Bankok
United Kingdom	The Bristol Haematology and Oncology Centre	Bristol
United Kingdom	Edinburgh Cancer Centre Western General Hospital	Edinburgh
United Kingdom	Beatson West of Scotland Cancer Centrel	Glasgow
United Kingdom	Guy's and St Thomas' NHS, Westminister Bridge Road	London
United Kingdom	Nottingham City Hospital	Nottingham
United Kingdom	Royal Marsden NHS Foundation Trust	Sutton	Surrey
United States	Lehigh Valley Physician Group-Hematology-Oncology Associates	Allentown	Pennsylvania
United States	Dent Neurosciences Research Institute	Amherst	New York
United States	University of Michigan Health System	Ann Arbor	Michigan
United States	Anne Arundel Medical Center	Annapolis	Maryland
United States	Atlanta Cancer Care	Atlanta	Georgia
United States	Winship Cancer Institute, Emory University School of Medicine	Atlanta	Georgia
United States	Georgia Regents University	Augusta	Georgia
United States	Texas Oncology Midtwon	Austin	Texas
United States	Johns Hopkins University School of Medicine	Baltimore	Maryland
United States	Mary Bird Perkins Cancer Center	Baton Rouge	Louisiana
United States	Center for Cancer and Blood Disorders, PC	Bethesda	Maryland
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Dana-Farber Cancer Institute and Mass General Hospital	Boston	Massachusetts
United States	Montefiore Medical Center	Bronx	New York
United States	New York Methodist Hospital	Brooklyn	New York
United States	Fletcher Allen Health Care	Burlington	Vermont
United States	Medical University of South Carolina - Department of Neuroscience	Charleston	South Carolina
United States	University of Virginia Healthcare System	Charlottesville	Virginia
United States	Northwestern University Robert H. Lurie Comprehensive Cancer Center	Chicago	Illinois
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Chicago	Chicago	Illinois
United States	University of Cincinnati Cancer Institute	Cincinnati	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	University Hospitals, Case Medical Center (Cleveland)	Cleveland	Ohio
United States	Ellis Fischel Cancer Center	Columbia	Missouri
United States	Ohio State University	Columbus	Ohio
United States	Baylor Research Institute	Dallas	Texas
United States	City of Hope Cancer Center	Duarte	California
United States	The Preston Robert Tisch Brain Tumor Center at Duke University Medical Center	Durham	North Carolina
United States	New Jersey Neuroscience Institute, JFK Medical Center	Edison	New Jersey
United States	North Shore University Health System	Evanston	Illinois
United States	University of Florida	Gainesville	Florida
United States	The Long Island Brain Tumor Center at Neurology Surgery, P.C.	Great Neck	New York
United States	John Theurer Cancer Center at Hackensack University Medical Center	Hackensack	New Jersey
United States	Hartford Hospital	Hartford	Connecticut
United States	Kaiser Permanente Hawaii Moanalua Medical Center	Honolulu	Hawaii
United States	The Methodist Neurological Institute	Houston	Texas
United States	University of Tennessee Medical Center - Knoxville	Knoxville	Tennessee
United States	UC San Diego Moores Cancer Center	La Jolla	California
United States	Edward W. Sparrow Hospital Association - Sparrow Regional Cancer Center	Lansing	Michigan
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	University of Kentucky	Lexington	Kentucky
United States	Southeast Nebraska Cancer Center	Lincoln	Nebraska
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Monmouth Medical Center	Long Branch	New Jersey
United States	USC Norris Comprehensive Cancer Center	Los Angeles	California
United States	Norton Cancer Institute	Louisville	Kentucky
United States	University of Wisconsin Paul P Carbone Comprehensive Cancer Center	Madison	Wisconsin
United States	North Shore University Hospital	Manhasset	New York
United States	Loyola University Medical Center	Maywood	Illinois
United States	Mount Sinai Medical Center, Comprehensive Cancer Center	Miami Beach	Florida
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Allina Health, Abbott Northwestern Hospital, John Nasseff Neuroscience Institute	Minneapolis	Minnesota
United States	University of South Alabama Mitchell Cancer Institute	Mobile	Alabama
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee
United States	Yale University Medical Center	New Haven	Connecticut
United States	Columbia University Medical Center - The Neurologic Institute of New York	New York	New York
United States	Weill Cornell Medical College	New York	New York
United States	Christiana Care Health Services	Newark	Delaware
United States	Chao Family Comprehensive Cancer Center	Orange	California
United States	MD Anderson Cancer Center Orlando	Orlando	Florida
United States	Temple University Hospital	Philadelphia	Pennsylvania
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Barrow Neurological Institute at St. Joseph's Hospital and Medical Center	Phoenix	Arizona
United States	University of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania
United States	West Penn. Allegheny Health System	Pittsburgh	Pennsylvania
United States	Pacific Neurosurgical	Portland	Oregon
United States	Providence Portland Medical Center, Oncology & Hematology Care	Portland	Oregon
United States	Kaiser Permanente, Redwood City Medical Center	Redwood City	California
United States	University of Rochester Medical Center	Rochester	New York
United States	University of California, Davis	Sacramento	California
United States	St. Mary's of Michigan Medical Center/Field Neurosciences Institute	Saginaw	Michigan
United States	Washington University in St. Louis	Saint Louis	Missouri
United States	University of Utah Department of Neurosurgery	Salt Lake City	Utah
United States	University of California, San Francisco	San Francisco	California
United States	Swedish Neuroscience Institute	Seattle	Washington
United States	University of Washington Medical Center	Seattle	Washington
United States	LSU Health Sciences Center, Feist-Weiller Cancer Center	Shreveport	Louisiana
United States	Stanford Cancer Institute, Stanford University	Stanford	California
United States	SUNY Upstate Medical University	Syracuse	New York
United States	Tampa General Hospital	Tampa	Florida
United States	University of Arizona Health Network	Tucson	Arizona
United States	Covenant Clinic / Iowa Spine and Brain Institute	Waterloo	Iowa
United States	Brain and Spine Surgeons of New York	White Plains	New York
United States	Wake Forest Baptist Health	Winston-Salem	North Carolina
United States	University of Massachusetts Memorial Medical Center	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Celldex Therapeutics

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Brazil,  Canada,  Colombia,  Czechia,  France,  Germany,  Greece,  Hungary,  India,  Israel,  Italy,  Mexico,  Netherlands,  New Zealand,  Peru,  Spain,  Switzerland,  Taiwan,  Thailand,  United Kingdom, 

References & Publications (1)

Weller M, Butowski N, Tran DD, Recht LD, Lim M, Hirte H, Ashby L, Mechtler L, Goldlust SA, Iwamoto F, Drappatz J, O'Rourke DM, Wong M, Hamilton MG, Finocchiaro G, Perry J, Wick W, Green J, He Y, Turner CD, Yellin MJ, Keler T, Davis TA, Stupp R, Sampson JH — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival	The primary efficacy endpoint of Overall Survival is defined as the number of months from randomization to the date of death (whatever the cause), and will be censored for patients who remain alive at completion of the study for patients with a gross total resection (~n=374). The overall survival of patients will be monitored and compared between the two study arms until the end of the study.	During treatment and every three months from end of treatment through end of study or approximately up to 5 years.
Secondary	Progression-free survival	Compare progression-free survival between the two treatment arms	Every 12 weeks from Day 1 through progression or initiation of other anti-cancer therapy
Secondary	Safety and Tolerability	Safety and tolerability will be measured by comparing the two arms in regards to vital sign measurement, physical and neurological examination, adverse events reporting, ECOG performance status, and EORTC core Quality of Life Questionnaire	Until day 28 of follow up