TroVax Renal Immunotherapy Survival Trial

Clear Cell Renal Carcinoma Clinical 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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00397345
• Other study ID #: TV3/001/06
• Status: Completed
• Phase: Phase 3
• Start date: September 2006
• Est. completion date: December 2009

Study information

• Verified date: October 2020
• Source: Oxford BioMedica
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 733
• Est. completion date: December 2009
• Est. primary completion date: December 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Renal Cell
• Clear Cell Renal Carcinoma
• Kidney Neoplasms

Intervention

Biological:
• Trovax
1ml IM injection 2-8 weeks apart.
• Placebo
Placebo
• Standard of care therapy
subcutaneous low dose IL-2, interferon-a or sunitinib

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Oxford BioMedica	Sanofi

Countries where clinical trial is conducted

United States,  France,  Germany,  Israel,  Poland,  Romania,  Russian Federation,  Spain,  Ukraine,  United Kingdom, 

References & Publications (1)

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-cont — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	overall survival		18 months