TroVax Renal Immunotherapy Survival Trial

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.

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.

Study Overview

• Status: Completed
• Conditions: Clear Cell Renal Carcinoma
• Intervention / Treatment: Biological: Placebo; Biological: Trovax; Biological: Standard of care therapy

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.

• Study Type: Interventional
• Enrollment (Actual): 733
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Besancon, France, 25030
    • CHU Besançon Hôpital Minjoz
  • Caen, France, 14076
    • Centre François Baclesse
  • Caen, France, 14076
    • Centre François Baclesse-CLCC-Caen
• Germany
  • Dresden, Germany, 01307
    • Universitätsklinikum C.G. Carus TU Dresden
• Israel
  • Haifa, Israel, 31096
    • Oncology institute , Rambam /health Care Campus
  • Kfar Saba, Israel, 44281
    • Meir Medical Center
  • Petach Tikva, Israel, 49100
    • Oncology department Rabin Medical center
  • Tel Aviv, Israel, 64239
    • Tel Aviv Sourasky Medical Center
  • Tel- Hashomer, Israel, 52621
    • Oncology institute , The Chaim Sheba Medical center
  • Zerifin
    • Be'er Ya'aqov, Zerifin, Israel, 70300
      • Oncology department, Assaf Harofeh Medical Center
• Poland
  • Gdańsk, Poland, 80-952
    • IIndependent Public Hospital #1- , Oncology and Radiotherapy Dept
  • Kielce, Poland, 25-734
    • Holycross Oncology Center in Kielce, Department of Urology
  • Krakow, Poland, 31-115
    • Maria Sklodowska-Curie Memorial Institute, Oncology Center Kraków Clinic Systemic and Generalized Neoplasms
  • Kraków, Poland, 31-501
    • Independent Public Health Care Institution University Hospital in Krakow, Department of Oncology
  • Poznan, Poland, 61-848
    • Lord's Transfiguration Independent Hospital Medical Academy Poznań
  • Szczecin, Poland, 70-111
    • Independent Public Clinical Hospital #2 - Pomeranian Medical Academy in Szczecin, Urology Clinic
  • Warsaw, Poland, 02-781
    • Maria Sklodowska-Curie Memorial Institute, Oncology Center in Warsaw, Clinic of Neoplasms of Urinary System
  • Warsaw,, Poland, 00-909
    • Military Institute of Medicine, Department of Oncology
  • Wrocław, Poland, 51-124
    • Regional Specialistic Hospital in Wrocław, Department of Urology
• Romania
  • Arad,, Romania, 310175
    • Private Medical Centre
  • Bucharest, Romania
    • "Prof. Dr. Th. Burghele" Clinical Hospital, Urology Clinic
  • Bucharest,, Romania, 022328
    • Fundeni Clinical Institute - Urology Department
  • Bucharest,, Romania, 041345
    • Dinu Uromedica
  • Bucharest,, Romania, 050659,
    • "Prof. Dr. Th. Burghele" Clinical Hospital, Urology Clinic
  • Cluj-Napoca, Romania, 400015,
    • "I. Chiricuta" Institute of Oncology
  • Cluj-Napoca,, Romania, 400420
    • E-URO Medical Center
  • Constanţa, Romania, 900635
    • Provita Center SRL
  • Sibiu,, Romania, 550245
    • Sibiu Clinical County Hospital - Urology Clinic
  • Timisoara,, Romania, 300239
    • Oncomed Srl
• Russian Federation
  • Arkhangelsk, Russian Federation, 163045
    • State Medical Institution: Arkhangelsk Regional Clinical Oncological Center, Surgery Department 7.
  • Chelyabinsk, Russian Federation, 454087
    • Chelyabinsk Regional Oncological Center, Chemotherapy Department
  • Chelyabinsk, Russian Federation, 454087
    • State Therapeutical and Prophylactic Institution: Chelyabinsk Regional Oncological Center,
  • Krasnodar, Russian Federation, 350040
    • Municipal Medical Institution: Oncological Center, Chemotherapy Department
  • Moscow, Russian Federation, 115478
    • State Institution: Russian Oncological Research Center n.a. N.N. Blokhin of the Russian Academy of Medical Sciences, Department of Urology
  • Moscow, Russian Federation, 117997
    • Russian Research Center of Roentgenology & Radiology , Surgery Department
  • Moscow, Russian Federation, 117997
    • Russian State Medical University under the Federal Agency for Healthcare and Social Development, Department of Radiology Daignostics and Radiology Therapy
  • Moscow, Russian Federation, 117997
    • Russian State Medical University under the Federal Agency for Healthcare and Social Development, Department of Urology and Surgical Nephrology
  • Moscow, Russian Federation, 125284
    • Moscow Research Oncological Institute n.a. P.A. Hertzen, Urology Departmen
  • Moscow, Russian Federation, 129110
    • Regional Research Clinical Institute n.a M.F. Vladimirskiy, Urology Department #1
  • Moscow, Russian Federation, 129128
    • Non-State Medical Institution:Central Clinical Hospital
  • Murmansk, Russian Federation, 183047
    • Murmansk Regional Oncological Center, Oncology Department #5
  • Nizhny Novgorod, Russian Federation, 603001
    • Privolzhsky County Medical Center
  • Nizhny Novgorod, Russian Federation, 603081
    • State Institution of Nizhny Novgorod Region: "Nizhny Novgorod Oncology Center", Department of Oncology #5 (for chemotherapy treatment)
  • Obninsk, Russian Federation, 249036
    • Medical Radiological Research Center under the Russian Academy of Medical Sciences, Department of Urology
  • Omsk, Russian Federation, 644013
    • State Medical Institution: Omsk Regional Oncological Center, Chemotherapy Department
  • Orel, Russian Federation, 302020
    • Regional State Medical Institution:"Orel Oncological Center", Oncology Department #5
  • Orenburg, Russian Federation, 460021
    • Orenburg Regional Clinical Oncological Center, Chemotherapy Department
  • Pyatigorsk, Russian Federation, 357500
    • Pyatigorsk Branch of Stavropol Territorial Clinical Oncological Center (State Medical Institution), Outpatient Department
  • Rostov-on-Don, Russian Federation, 344022
    • Rostov State Medical University under the Federal Agency for Healthcare and Social Development, Department of Urology
  • Ryazan, Russian Federation, 390011
    • Regional Clinical Oncological Center, Surgery Department
  • Samara, Russian Federation, 443066
    • Samara Regional Oncology Center, Chemotherapy Department
  • Sochi, Russian Federation, 354057
    • "Oncological Center", Department of Haematology and Chemotherapy
  • St Petersburg, Russian Federation, 194354
    • Municipal Multi-Speciality Hospital #2, Department of Urology
  • St Petersburg, Russian Federation, 196247
    • Municipal Hospital #26, Department Of Urology
  • St Petersburg, Russian Federation, 197758
    • "Central Research Institute of Roentgenology & Radiology Federal Agency Healthcare Social Development"
  • St Petersburg, Russian Federation, 197758
    • Department of Biotherapy and Bone Marrow Transplantation
  • St. Petersburg, Russian Federation, 194100
    • St. Petersburg State Pediatric Medical Academy
  • St. Petersburg, Russian Federation, 194291
    • Department of Urology
  • St. Petersburg, Russian Federation, 198205
    • St. Petersburg State Medical Institution: Municipal Hospital #15, Urology Department
  • St.Petersburg, Russian Federation, 194354
    • St. Petersburg State Medical Institution: Municipal Multi-Speciality Hospital #2, Department of Functional Diagnostics
  • Stavropol, Russian Federation, 355047
    • State Medical Institution: Stavropol Territorial Clinical Oncological Center, Department of Urology
  • Tambov, Russian Federation, 392013
    • State Medical Institution: Tambov Regional Oncological Center, Surgery Department
  • Tomsk, ,, Russian Federation, 634050
    • State Higher Educational Institution: Siberian State Medical University, Department of Urology
  • Ufa, Russian Federation, 634050
    • Bashkir State Medical University, Urology Department
  • Yaroslavl, Russian Federation, 150054
    • State Medical Institution of Yaroslavl Region
  • Yoshkar-Ola, Russian Federation, 424037
    • State Institution of Mariy El Republic: "Republican Clinical Hospital", Department Of Urology
  • Leningrad Region
    • St Petersburg, Leningrad Region, Russian Federation, 188663
      • Leningrad Regional Oncological Center, Surgical Department #3
  • Republic Of Karelia
    • Petrozavodsk, Republic Of Karelia, Russian Federation, 185007
      • Republican Oncology Center" under the Ministry of Healthcare,
  • Republic Of Tatarstan
    • Kazan, Republic Of Tatarstan, Russian Federation, 420029
      • State Medical Institution of Healthcare: Clinical Oncological Center under the Ministry of Healthcare of the Republic of Tatarstan, Chemotherapy Department
• Spain
  • Barakaldo, Spain, 48903
    • Hospital de Cruces
  • Barcelona, Spain, 080025
    • Hospital Santa Creu i Sant Pau Hospital Nuevo-Servicio de Oncologia Medica
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon Y Cajal
  • Santander, Spain, 39008
    • Hospital Marques de Valdecilla Consultas de Oncologia 1st planta
  • Madrid
    • Leganes, Madrid, Spain, S
      • Hospital Severo Ochoa, Servicio de Oncologia - Primera planta
• Ukraine
  • Chernivtsi, Ukraine, 58000,
    • Bukovyna State Medical University, Department of Oncology, Radiodiagnostics and Radiotherapy
  • Dnepropetrovsk, Ukraine, 49005
    • Dnepropetrovsk State Medical Academy, Department of Urology
  • Dnepropetrovsk, Ukraine, 49044
    • Dnepropetrovsk State Medical Academy, Oncology, Radiodiagnostics and Radiotherapy Department
  • Donetsk, Ukraine, 83092
    • Donetsk Regional Antitumor Center, Urology Department
  • Ivano-Frankivs'k, Ukraine, 76000
    • Ivano-Frankovsk State Medical University; Oncology Department
  • Kharkov, Ukraine, 61037
    • Kharkov Regional Clinical Urology and Nephrology Center, Oncourology Department
  • Kharkov, Ukraine, 61176
    • Kharkov Medical Academy of Postgraduate Education, Oncology and Pediatric Oncology Department
  • Kiev, Ukraine, 04053
    • Urology Institute under the Ukrainian Academy of Medical Sciences, Oncourology Department
  • Kiev, Ukraine, 04053
    • Urology Institute under the Ukrainian Academy of Medical Sciences, Plastic and Reconstructive Urology Department
  • Krivoi Rog, Ukraine, 50048
    • Regional Public Institution: Krivoy Rog Oncological Center, Chemotherapy Department
  • Lugansk, Ukraine, 91047
    • Lugansk Regional Clinical Oncological Center, Urology Department
  • Lviv, Ukraine, 79010
    • Crimea State Medical University n.a. S.I. Georgievsky, Course in Urology at the Faculty Surgery#1 Department
  • Odessa, Ukraine, 65074
    • Odessa State Medical University;
  • Simferopol, Ukraine, 95023
    • Crimean Republican Clinical Oncological Center, Chemotherapy Department
  • Uzhorod, Ukraine, 88000
    • Uzhgorod National University,
  • Zaporozhye, Ukraine, 69096
    • Zaporozhye Medical Academy of Postgraduate Education, Oncology Department
  • Zaporozhye, Ukraine, 69600
    • Zaporozhye Medical Academy of Postgraduate Education, Urology Department
• United Kingdom
  • Bournemouth, United Kingdom, BH7 7DW
    • The Royal Bournemouth Hospital
  • Bristol, United Kingdom, BS2 8ED
    • Bristol Haematology and Oncology Centre
  • Glasgow, United Kingdom, G11 6NT
    • Beatson Oncology Centre
  • Guildford, United Kingdom, GU2 7XX
    • St Luke's Cancer Centre, Royal Surrey County Hospital
  • Leeds, United Kingdom, LS9 7TF
    • St. James University Hospital
  • Manchester, United Kingdom, M20 4BX
    • Christie Hospital NHS Trust
  • Middlesbrough, United Kingdom, TS4 3BW
    • The James Cook University Hospital
  • Nottingham, United Kingdom, NG5 1PB
    • University of Nottingham
  • Oxford, United Kingdom, OX3 7LJ
    • The Churchill Hospital
  • Sheffield, United Kingdom, S10 2SJ
    • Weston Park Hospital
  • Swansea, United Kingdom, SA2 8QA
    • The South West Wales Cancer Institute
  • Wolverhampton, United Kingdom, WV10 0QP
    • New Cross Hospital
  • Middlesex
    • Northwood, Middlesex, United Kingdom, HA6 2RN
      • Mount Vernon Cancer Centre
  • N. Ireland
    • Belfast, N. Ireland, United Kingdom
      • Belfast City Hospital
  • Wirral
    • Bebington, Wirral, United Kingdom, CH63 4JY.
      • Clatterbridge Centre for Oncology
• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
      • AZ Cancer Center
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Little Rock Hematology / Oncology Associates, P.A.
  • California
    • La Jolla, California, United States, 92093
      • La Jolla, CA
    • Los Angeles, California, United States, 90025
      • The Angeles Clinic and Reseach Institute
    • Los Angeles, California, United States, 90027
      • 1300 N. Vermont Ave
    • Los Angeles, California, United States, 90095
      • UCLA Urology/Oncology
    • San Diego, California, United States, 92121
      • Scripps Cancer Center
    • San Diego, California, United States, 92823
      • Sharp Health Care
  • Colorado
    • Aurora, Colorado, United States, 80045
      • UCHSC
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Washington Cancer Center
  • Florida
    • Fort Lauderdale, Florida, United States, 33308
      • Broward Oncology Associates
    • Saint Petersburg, Florida, United States, 33710
      • SCORE Physician Alliance
    • Saint Petersburg, Florida, United States, 33709
      • SCORE Physician Alliance
    • Tampa, Florida, United States, 33612
      • H. Lee Moffitt Cancer Center & Research Institute
  • Georgia
    • Augusta, Georgia, United States, 30901
      • Augusta Oncology Associates
    • Canton, Georgia, United States, 301115
      • SMO-USA Inc.
  • Idaho
    • Coeur d'Alene, Idaho, United States, 83814
      • North Idaho Cancer Centre
  • Illinois
    • Olympia Fields, Illinois, United States, 60461
      • Patricia A. Joyce Cancer Institute
    • Skokie, Illinois, United States, 60076
      • Edward H Kaplan and Associates
  • Indiana
    • Indianapolis, Indiana, United States, 46107
      • St Francis Hospital
    • New Albany, Indiana, United States, 47150
      • Cancer Care Centre of Indiana
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Clinic Foundation
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System / Josephine Ford Cancer Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University Minnesota Fairview Medical Center
  • Mississippi
    • Tupelo, Mississippi, United States, 38801
      • Haematology and Oncology Associates at Bridgeport
  • Montana
    • Billings, Montana, United States, 59101
      • Charleston Hematology and Oncology Associates,
    • Billings, Montana, United States, 59107
      • Billings Clinical Research Center
  • Nevada
    • Las Vegas, Nevada, United States, 89109
      • Freedman Urology
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Norris Cotton Cancer Center / Dartmouth-Hitchcock Medical Center
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • The Cancer Center @ HUMC
  • New York
    • New York, New York, United States, 10032
      • Columbia Presbyterian Medical Center
    • Rochester, New York, United States, 14623
      • Pluta Cancer Centre
  • Ohio
    • Canton, Ohio, United States, 30309
      • Piedmont Hospital, Inc.
    • Columbus, Ohio, United States, 43214
      • Riverside Cancer Centre
    • Columbus, Ohio, United States, 43235
      • Heamatology and Oncology Associates Inc.
    • Sylvania, Ohio, United States, 43560
      • Flower Hospital/ Promedica Health System
  • Oregon
    • Springfield, Oregon, United States, 97477
      • Oregon Urology Institute
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Cancer Centre of the Carolinas
    • Myrtle Beach, South Carolina, United States, 29572
      • Carolina Urologic Research Center
  • Texas
    • Galveston, Texas, United States, 77555-0565
      • University of Texas Medical Branch
    • Houston, Texas, United States, 77030
      • The Methodist Hospital
    • McAllen, Texas, United States, 78503
      • Urology Associates of South Texas
  • Virginia
    • Abingdon, Virginia, United States, 24211
      • Cancer Outreach Associates PC
    • Norfolk, Virginia, United States, 23502
      • Virginia Oncology Associates
  • Washington
    • Seattle, Washington, United States, 98109
      • Seattle Cancer Care Alliance
    • Tacoma, Washington, United States, 98109
      • Madigan Army Medical Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Biological: Placebo; Placebo; Biological: Standard of care therapy; subcutaneous low dose IL-2, interferon-α or sunitinib
Experimental: Trovax	Biological: Trovax; 1ml IM injection 2-8 weeks apart.; Biological: Standard of care therapy; subcutaneous low dose IL-2, interferon-α or sunitinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
overall survival	18 months

Collaborators and Investigators

• Sponsor: Oxford BioMedica
• Collaborators: Sanofi

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: September 1, 2006
• Primary Completion (Actual): December 1, 2009
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: November 8, 2006
• First Submitted That Met QC Criteria: November 8, 2006
• First Posted (Estimate): November 9, 2006

Study Record Updates

• Last Update Posted (Actual): October 19, 2020
• Last Update Submitted That Met QC Criteria: October 9, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: immunotherapy; cancer; survival; metastatic; Kidney; Renal; TroVax
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Carcinoma, Renal Cell
• Other Study ID Numbers: TV3/001/06