Clinical trial NCT00397345: TroVax Renal Immunotherapy Survival Trial
Official title: Randomised,Double-blind,Placebo-controlled,Parallel Group Study TroVax, Added to First-line Standard of Care, Prolongs Survival of Patients With Locally Advanced or Metastatic Clear Cell Renal Adenocarcinoma.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Clear Cell Renal Carcinoma
Keywords: Renal
TroVax
survival
metastatic
Kidney
cancer
immunotherapy
Lead sponsor: Oxford BioMedica
Sponsor class: INDUSTRY
Collaborators: name: Sanofi
First posted: 2006-11-09
Enrollment: 733
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: The purpose of this study is to investigate whether TroVax, when added to first line standard of care therapy, improves survival for patients with locally advanced or metastatic clear cell renal adenocarcinoma.

Detailed description: This is an international, randomised, double blind, placebo controlled, parallel group study to investigate whether a minimum of three doses of TroVax® added to first-line standard of care therapy, prolongs the survival of patients with locally advanced or metastatic renal clear cell adenocarcinoma.

The primary endpoint is survival. The study is designed to be pragmatic, limiting additional study related investigations to a minimum. Protocol mandated scans and X-rays are limited to two time points (baseline and week 26) to permit comparison of the percentage of patients with progressive disease at 6 months as a secondary efficacy endpoint. Six months was selected based on review of published literature indicating that progressive disease was commonly observed by 26 weeks in patients with renal cancer. Endpoints such as tumour response by RECIST are considered of secondary importance to survival and will be determined by radiological examinations ordered at the discretion of the investigator based on the clinical status of the patient and will be based the interpretation of the patient's care-team (investigator and local radiologist).

After signing the study informed consent form and meeting the baseline enrolment criteria patients will be assigned by the investigator (their physician) to one of the following defined first-line standard of care regimens based on what is best for the patient and consistent with local practice:

1. subcutaneous low dose IL-2
2. interferon-α (excluding pegylated IFNα)
3. sunitinib

TroVax® is administered at a dose of 1E9TCID50/ml in 1ml by injection into the deltoid muscle of the upper arm at regular intervals up to 8 weeks apart up to a maximum of 13 doses.

Eligibility criteria: Inclusion Criteria:

* Signed informed consent. The patient must be competent to give written informed consent and comply with the protocol requirements.
* Locally advanced or metastatic, histologically proven clear cell renal carcinoma.
* Primary tumour surgically removed (some residual advanced primary tumour may remain).
* At least four weeks post surgery or radiotherapy.
* First-line. No prior therapy for renal cancer except surgery or radiotherapy.
* Measurable disease.
* Aged 18 years or more.
* Patient expected to survive a minimum of 12 weeks (i.e. in the opinion of the investigator there is a \>90% probability that the patient will survive \>12 weeks if treated with the selected standard of care).
* Free of clinically apparent autoimmune disease (including no prior confirmed diagnosis or treatment for autoimmune disease including Systemic Lupus Erythematosis, Grave's disease, Hashimoto's thyroiditis, multiple sclerosis, insulin dependant diabetes mellitus or systemic (non-joint) manifestations of rheumatoid disease).
* Total white cell count ≥ 3 x 109/L and lymphocyte count ≥1 x 109/L.
* Serum creatinine ≤1.5 times the upper limit of normal.
* Bilirubin ≤ 2 times the upper limit of normal and an SGPT of ≤ 4 times the upper limit of normal.
* Women must be either post menopausal, or rendered surgically sterile or, if of child bearing potential, must have been practising a reliable form of contraception (oral contraception + a barrier method) for at least three months prior to the first dose of TroVax® and must continue while they are being treated with TroVax®. Men must practise a reliable form of contraception (barrier or vasectomy) while they are being treated with TroVax®.
* No acute changes on 12-lead ECG.
* Ejection fraction documented as not less than 45% or no clinical suspicion that cardiac ejection fraction is less than 45%.(If clinical suspicion exists the ejection fraction should be measured according to local site procedures).
* Karnofsky performance status of ≥ 80%.

Exclusion Criteria:

* Cerebral metastases. (Known from previous investigations or clinically detectable).
* Previous exposure to TroVax®.
* Serious infections within the 28 days prior to entry to the trial.
* Known to test positive for HIV or hepatitis B or C.
* Life threatening illness unrelated to cancer.
* History of allergic response to previous vaccinia vaccinations.
* Known allergy to egg proteins.
* Known hypersensitivity to neomycin.
* Participation in any other clinical trial of a licensed or unlicensed drug within the previous 30 days or during the course of this trial.
* Previous malignancies within the last 10 years other than successfully treated squamous carcinoma of the skin or in situ carcinoma of the cervix treated with cone biopsy.
* Previous history of major psychiatric disorder requiring hospitalization or any current psychiatric disorder that would impede the patient's ability to provide informed consent or to comply with the protocol.
* Oral corticosteroid use unless prescribed as replacement therapy in the case of adrenal insufficiency.
* Ongoing use of agents listed in locally approved prescribing information as causing immunosuppression.
* Prior history of organ transplantation.
* Pregnancy or lactation.

Primary outcomes:
measure: overall survival
timeFrame: 18 months
Secondary outcomes:
Other outcomes:
Locations:
city: Tucson
country: United States
facility: AZ Cancer Center
state: Arizona
city: Little Rock
country: United States
facility: Little Rock Hematology / Oncology Associates, P.A.
state: Arkansas
city: La Jolla
country: United States
facility: La Jolla, CA
state: California
city: Los Angeles
country: United States
facility: The Angeles Clinic and Reseach Institute
state: California
city: Los Angeles
country: United States
facility: 1300 N. Vermont Ave
state: California
city: Los Angeles
country: United States
facility: UCLA Urology/Oncology
state: California
city: San Diego
country: United States
facility: Scripps Cancer Center
state: California
city: San Diego
country: United States
facility: Sharp Health Care
state: California
city: Aurora
country: United States
facility: UCHSC
state: Colorado
city: Washington
country: United States
facility: Washington Cancer Center
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: Broward Oncology Associates
state: Florida
city: Saint Petersburg
country: United States
facility: SCORE Physician Alliance
state: Florida
city: Saint Petersburg
country: United States
facility: SCORE Physician Alliance
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center & Research Institute
state: Florida
city: Augusta
country: United States
facility: Augusta Oncology Associates
state: Georgia
city: Canton
country: United States
facility: SMO-USA Inc.
state: Georgia
city: Coeur d'Alene
country: United States
facility: North Idaho Cancer Centre
state: Idaho
city: Olympia Fields
country: United States
facility: Patricia A. Joyce Cancer Institute
state: Illinois
city: Skokie
country: United States
facility: Edward H Kaplan and Associates
state: Illinois
city: Indianapolis
country: United States
facility: St Francis Hospital
state: Indiana
city: New Albany
country: United States
facility: Cancer Care Centre of Indiana
state: Indiana
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Detroit
country: United States
facility: Henry Ford Health System / Josephine Ford Cancer Center
state: Michigan
city: Minneapolis
country: United States
facility: University Minnesota Fairview Medical Center
state: Minnesota
city: Tupelo
country: United States
facility: Haematology and Oncology Associates at Bridgeport
state: Mississippi
city: Billings
country: United States
facility: Charleston Hematology and Oncology Associates,
state: Montana
city: Billings
country: United States
facility: Billings Clinical Research Center
state: Montana
city: Las Vegas
country: United States
facility: Freedman Urology
state: Nevada
city: Lebanon
country: United States
facility: Norris Cotton Cancer Center / Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Hackensack
country: United States
facility: The Cancer Center @ HUMC
state: New Jersey
city: New York
country: United States
facility: Columbia Presbyterian Medical Center
state: New York
city: Rochester
country: United States
facility: Pluta Cancer Centre
state: New York
city: Canton
country: United States
facility: Piedmont Hospital, Inc.
state: Ohio
city: Columbus
country: United States
facility: Riverside Cancer Centre
state: Ohio
city: Columbus
country: United States
facility: Heamatology and Oncology Associates Inc.
state: Ohio
city: Sylvania
country: United States
facility: Flower Hospital/ Promedica Health System
state: Ohio
city: Springfield
country: United States
facility: Oregon Urology Institute
state: Oregon
city: Greenville
country: United States
facility: Cancer Centre of the Carolinas
state: South Carolina
city: Myrtle Beach
country: United States
facility: Carolina Urologic Research Center
state: South Carolina
city: Galveston
country: United States
facility: University of Texas Medical Branch
state: Texas
city: Houston
country: United States
facility: The Methodist Hospital
state: Texas
city: McAllen
country: United States
facility: Urology Associates of South Texas
state: Texas
city: Abingdon
country: United States
facility: Cancer Outreach Associates PC
state: Virginia
city: Norfolk
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Tacoma
country: United States
facility: Madigan Army Medical Centre
state: Washington
city: Besancon
country: France
facility: CHU Besançon Hôpital Minjoz
city: Caen
country: France
facility: Centre Francois Baclesse
city: Caen
country: France
facility: Centre François Baclesse-CLCC-Caen
city: Dresden
country: Germany
facility: Universitätsklinikum C.G. Carus TU Dresden
city: Be'er Ya'aqov
country: Israel
facility: Oncology department, Assaf Harofeh Medical Center
state: Zerifin
city: Haifa
country: Israel
facility: Oncology institute , Rambam /health Care Campus
city: Kfar Saba
country: Israel
facility: Meir Medical Center
city: Petach Tikva
country: Israel
facility: Oncology department Rabin Medical center
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Tel- Hashomer
country: Israel
facility: Oncology institute , The Chaim Sheba Medical center
city: Gdańsk
country: Poland
facility: IIndependent Public Hospital #1- , Oncology and Radiotherapy Dept
city: Kielce
country: Poland
facility: Holycross Oncology Center in Kielce, Department of Urology
city: Krakow
country: Poland
facility: Maria Sklodowska-Curie Memorial Institute, Oncology Center Kraków Clinic Systemic and Generalized Neoplasms
city: Kraków
country: Poland
facility: Independent Public Health Care Institution University Hospital in Krakow, Department of Oncology
city: Poznan
country: Poland
facility: Lord's Transfiguration Independent Hospital Medical Academy Poznań
city: Szczecin
country: Poland
facility: Independent Public Clinical Hospital #2 - Pomeranian Medical Academy in Szczecin, Urology Clinic
city: Warsaw,
country: Poland
facility: Military Institute of Medicine, Department of Oncology
city: Warsaw
country: Poland
facility: Maria Sklodowska-Curie Memorial Institute, Oncology Center in Warsaw, Clinic of Neoplasms of Urinary System
city: Wrocław
country: Poland
facility: Regional Specialistic Hospital in Wrocław, Department of Urology
city: Arad,
country: Romania
facility: Private Medical Centre
city: Bucharest,
country: Romania
facility: Fundeni Clinical Institute - Urology Department
city: Bucharest,
country: Romania
facility: Dinu Uromedica
city: Bucharest,
country: Romania
facility: "Prof. Dr. Th. Burghele" Clinical Hospital, Urology Clinic
city: Bucharest
country: Romania
facility: "Prof. Dr. Th. Burghele" Clinical Hospital, Urology Clinic
city: Cluj-Napoca,
country: Romania
facility: E-URO Medical Center
city: Cluj-Napoca
country: Romania
facility: "I. Chiricuta" Institute of Oncology
city: Constanţa
country: Romania
facility: Provita Center SRL
city: Sibiu,
country: Romania
facility: Sibiu Clinical County Hospital - Urology Clinic
city: Timisoara,
country: Romania
facility: Oncomed SRL
city: St Petersburg
country: Russian Federation
facility: Leningrad Regional Oncological Center, Surgical Department #3
state: Leningrad Region
city: Petrozavodsk
country: Russian Federation
facility: Republican Oncology Center" under the Ministry of Healthcare,
state: Republic Of Karelia
city: Kazan
country: Russian Federation
facility: State Medical Institution of Healthcare: Clinical Oncological Center under the Ministry of Healthcare of the Republic of Tatarstan, Chemotherapy Department
state: Republic Of Tatarstan
city: Arkhangelsk
country: Russian Federation
facility: State Medical Institution: Arkhangelsk Regional Clinical Oncological Center, Surgery Department 7.
city: Chelyabinsk
country: Russian Federation
facility: Chelyabinsk Regional Oncological Center, Chemotherapy Department
city: Chelyabinsk
country: Russian Federation
facility: State Therapeutical and Prophylactic Institution: Chelyabinsk Regional Oncological Center,
city: Krasnodar
country: Russian Federation
facility: Municipal Medical Institution: Oncological Center, Chemotherapy Department
city: Moscow
country: Russian Federation
facility: State Institution: Russian Oncological Research Center n.a. N.N. Blokhin of the Russian Academy of Medical Sciences, Department of Urology
city: Moscow
country: Russian Federation
facility: Russian Research Center of Roentgenology & Radiology , Surgery Department
city: Moscow
country: Russian Federation
facility: Russian State Medical University under the Federal Agency for Healthcare and Social Development, Department of Radiology Daignostics and Radiology Therapy
city: Moscow
country: Russian Federation
facility: Russian State Medical University under the Federal Agency for Healthcare and Social Development, Department of Urology and Surgical Nephrology
city: Moscow
country: Russian Federation
facility: Moscow Research Oncological Institute n.a. P.A. Hertzen, Urology Departmen
city: Moscow
country: Russian Federation
facility: Regional Research Clinical Institute n.a M.F. Vladimirskiy, Urology Department #1
city: Moscow
country: Russian Federation
facility: Non-State Medical Institution:Central Clinical Hospital
city: Murmansk
country: Russian Federation
facility: Murmansk Regional Oncological Center, Oncology Department #5
city: Nizhny Novgorod
country: Russian Federation
facility: Privolzhsky County Medical Center
city: Nizhny Novgorod
country: Russian Federation
facility: State Institution of Nizhny Novgorod Region: "Nizhny Novgorod Oncology Center", Department of Oncology #5 (for chemotherapy treatment)
city: Obninsk
country: Russian Federation
facility: Medical Radiological Research Center under the Russian Academy of Medical Sciences, Department of Urology
city: Omsk
country: Russian Federation
facility: State Medical Institution: Omsk Regional Oncological Center, Chemotherapy Department
city: Orel
country: Russian Federation
facility: Regional State Medical Institution:"Orel Oncological Center", Oncology Department #5
city: Orenburg
country: Russian Federation
facility: Orenburg Regional Clinical Oncological Center, Chemotherapy Department
city: Pyatigorsk
country: Russian Federation
facility: Pyatigorsk Branch of Stavropol Territorial Clinical Oncological Center (State Medical Institution), Outpatient Department
city: Rostov-on-Don
country: Russian Federation
facility: Rostov State Medical University under the Federal Agency for Healthcare and Social Development, Department of Urology
city: Ryazan
country: Russian Federation
facility: Regional Clinical Oncological Center, Surgery Department
city: Samara
country: Russian Federation
facility: Samara Regional Oncology Center, Chemotherapy Department
city: Sochi
country: Russian Federation
facility: "Oncological Center", Department of Haematology and Chemotherapy
city: St Petersburg
country: Russian Federation
facility: Municipal Multi-Speciality Hospital #2, Department of Urology
city: St Petersburg
country: Russian Federation
facility: Municipal Hospital #26, Department Of Urology
city: St Petersburg
country: Russian Federation
facility: "Central Research Institute of Roentgenology & Radiology Federal Agency Healthcare Social Development"
city: St Petersburg
country: Russian Federation
facility: Department of Biotherapy and Bone Marrow Transplantation
city: St. Petersburg
country: Russian Federation
facility: St. Petersburg State Pediatric Medical Academy
city: St. Petersburg
country: Russian Federation
facility: Department of Urology
city: St. Petersburg
country: Russian Federation
facility: St. Petersburg State Medical Institution: Municipal Hospital #15, Urology Department
city: St.Petersburg
country: Russian Federation
facility: St. Petersburg State Medical Institution: Municipal Multi-Speciality Hospital #2, Department of Functional Diagnostics
city: Stavropol
country: Russian Federation
facility: State Medical Institution: Stavropol Territorial Clinical Oncological Center, Department of Urology
city: Tambov
country: Russian Federation
facility: State Medical Institution: Tambov Regional Oncological Center, Surgery Department
city: Tomsk, ,
country: Russian Federation
facility: State Higher Educational Institution: Siberian State Medical University, Department of Urology
city: Ufa
country: Russian Federation
facility: Bashkir State Medical University, Urology Department
city: Yaroslavl
country: Russian Federation
facility: State Medical Institution of Yaroslavl Region
city: Yoshkar-Ola
country: Russian Federation
facility: State Institution of Mariy El Republic: "Republican Clinical Hospital", Department Of Urology
city: Leganes
country: Spain
facility: Hospital Severo Ochoa, Servicio de Oncologia - Primera planta
state: Madrid
city: Barakaldo
country: Spain
facility: Hospital de Cruces
city: Barcelona
country: Spain
facility: Hospital Santa Creu i Sant Pau Hospital Nuevo-Servicio de Oncologia Medica
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Santander
country: Spain
facility: Hospital Marques de Valdecilla Consultas de Oncologia 1st planta
city: Chernivtsi
country: Ukraine
facility: Bukovyna State Medical University, Department of Oncology, Radiodiagnostics and Radiotherapy
city: Dnepropetrovsk
country: Ukraine
facility: Dnepropetrovsk State Medical Academy, Department of Urology
city: Dnepropetrovsk
country: Ukraine
facility: Dnepropetrovsk State Medical Academy, Oncology, Radiodiagnostics and Radiotherapy Department
city: Donetsk
country: Ukraine
facility: Donetsk Regional Antitumor Center, Urology Department
city: Ivano-Frankivs'k
country: Ukraine
facility: Ivano-Frankovsk State Medical University; Oncology Department
city: Kharkov
country: Ukraine
facility: Kharkov Regional Clinical Urology and Nephrology Center, Oncourology Department
city: Kharkov
country: Ukraine
facility: Kharkov Medical Academy of Postgraduate Education, Oncology and Pediatric Oncology Department
city: Kiev
country: Ukraine
facility: Urology Institute under the Ukrainian Academy of Medical Sciences, Oncourology Department
city: Kiev
country: Ukraine
facility: Urology Institute under the Ukrainian Academy of Medical Sciences, Plastic and Reconstructive Urology Department
city: Krivoi Rog
country: Ukraine
facility: Regional Public Institution: Krivoy Rog Oncological Center, Chemotherapy Department
city: Lugansk
country: Ukraine
facility: Lugansk Regional Clinical Oncological Center, Urology Department
city: Lviv
country: Ukraine
facility: Crimea State Medical University n.a. S.I. Georgievsky, Course in Urology at the Faculty Surgery#1 Department
city: Odessa
country: Ukraine
facility: Odessa State Medical University;
city: Simferopol
country: Ukraine
facility: Crimean Republican Clinical Oncological Center, Chemotherapy Department
city: Uzhorod
country: Ukraine
facility: Uzhgorod National University,
city: Zaporozhye
country: Ukraine
facility: Zaporozhye Medical Academy of Postgraduate Education, Oncology Department
city: Zaporozhye
country: Ukraine
facility: Zaporozhye Medical Academy of Postgraduate Education, Urology Department
city: Northwood
country: United Kingdom
facility: Mount Vernon Cancer Centre
state: Middlesex
city: Belfast
country: United Kingdom
facility: Belfast City Hospital
state: N. Ireland
city: Bebington
country: United Kingdom
facility: Clatterbridge Centre for Oncology
state: Wirral
city: Bournemouth
country: United Kingdom
facility: The Royal Bournemouth Hospital
city: Bristol
country: United Kingdom
facility: Bristol Haematology and Oncology Centre
city: Glasgow
country: United Kingdom
facility: Beatson Oncology Centre
city: Guildford
country: United Kingdom
facility: St Luke's Cancer Centre, Royal Surrey County Hospital
city: Leeds
country: United Kingdom
facility: St. James University Hospital
city: Manchester
country: United Kingdom
facility: Christie Hospital NHS Trust
city: Middlesbrough
country: United Kingdom
facility: The James Cook University Hospital
city: Nottingham
country: United Kingdom
facility: University of Nottingham
city: Oxford
country: United Kingdom
facility: The Churchill Hospital
city: Sheffield
country: United Kingdom
facility: Weston Park Hospital
city: Swansea
country: United Kingdom
facility: The South West Wales Cancer Institute
city: Wolverhampton
country: United Kingdom
facility: New Cross Hospital
Study officials:
References:
citation: Amato RJ, Hawkins RE, Kaufman HL, Thompson JA, Tomczak P, Szczylik C, McDonald M, Eastty S, Shingler WH, de Belin J, Goonewardena M, Naylor S, Harrop R. Vaccination of metastatic renal cancer patients with MVA-5T4: a randomized, double-blind, placebo-controlled phase III study. Clin Cancer Res. 2010 Nov 15;16(22):5539-47. doi: 10.1158/1078-0432.CCR-10-2082. Epub 2010 Sep 29.