TroVax Renal Immunotherapy Survival Trial

Sponsor

Oxford BioMedica (Industry)

Overall Status

Completed

CT.gov ID

NCT00397345

Collaborator

Sanofi (Industry)

733

Enrollment

152

Locations

Arms

Duration (Months)

4.8

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Clear Cell Renal Carcinoma	Biological: Trovax Biological: Placebo Biological: Standard of care therapy	Phase 3

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:

subcutaneous low dose IL-2
interferon-α (excluding pegylated IFNα)
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 Design

Study Type:

Interventional

Actual Enrollment :

733 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

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 Start Date :

Sep 1, 2006

Actual Primary Completion Date :

Dec 1, 2009

Actual Study Completion Date :

Dec 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
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
Placebo Comparator: Placebo	Biological: Placebo Placebo Biological: Standard of care therapy subcutaneous low dose IL-2, interferon-α or sunitinib

Arm

Intervention/Treatment

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

Placebo Comparator: Placebo

Biological: Placebo

Placebo

Biological: Standard of care therapy

subcutaneous low dose IL-2, interferon-α or sunitinib

Outcome Measures

Primary Outcome Measures

overall survival [18 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	AZ Cancer Center	Tucson	Arizona	United States	85724
2	Little Rock Hematology / Oncology Associates, P.A.	Little Rock	Arkansas	United States	72205
3	La Jolla, CA	La Jolla	California	United States	92093
4	The Angeles Clinic and Reseach Institute	Los Angeles	California	United States	90025
5	1300 N. Vermont Ave	Los Angeles	California	United States	90027
6	UCLA Urology/Oncology	Los Angeles	California	United States	90095
7	Scripps Cancer Center	San Diego	California	United States	92121
8	Sharp Health Care	San Diego	California	United States	92823
9	UCHSC	Aurora	Colorado	United States	80045
10	Washington Cancer Center	Washington	District of Columbia	United States	20010
11	Broward Oncology Associates	Fort Lauderdale	Florida	United States	33308
12	SCORE Physician Alliance	Saint Petersburg	Florida	United States	33709
13	SCORE Physician Alliance	Saint Petersburg	Florida	United States	33710
14	H. Lee Moffitt Cancer Center & Research Institute	Tampa	Florida	United States	33612
15	Augusta Oncology Associates	Augusta	Georgia	United States	30901
16	SMO-USA Inc.	Canton	Georgia	United States	301115
17	North Idaho Cancer Centre	Coeur d'Alene	Idaho	United States	83814
18	Patricia A. Joyce Cancer Institute	Olympia Fields	Illinois	United States	60461
19	Edward H Kaplan and Associates	Skokie	Illinois	United States	60076
20	St Francis Hospital	Indianapolis	Indiana	United States	46107
21	Cancer Care Centre of Indiana	New Albany	Indiana	United States	47150
22	Ochsner Clinic Foundation	New Orleans	Louisiana	United States	70121
23	Henry Ford Health System / Josephine Ford Cancer Center	Detroit	Michigan	United States	48202
24	University Minnesota Fairview Medical Center	Minneapolis	Minnesota	United States	55455
25	Haematology and Oncology Associates at Bridgeport	Tupelo	Mississippi	United States	38801
26	Charleston Hematology and Oncology Associates,	Billings	Montana	United States	59101
27	Billings Clinical Research Center	Billings	Montana	United States	59107
28	Freedman Urology	Las Vegas	Nevada	United States	89109
29	Norris Cotton Cancer Center / Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756
30	The Cancer Center @ HUMC	Hackensack	New Jersey	United States	07601
31	Columbia Presbyterian Medical Center	New York	New York	United States	10032
32	Pluta Cancer Centre	Rochester	New York	United States	14623
33	Piedmont Hospital, Inc.	Canton	Ohio	United States	30309
34	Riverside Cancer Centre	Columbus	Ohio	United States	43214
35	Heamatology and Oncology Associates Inc.	Columbus	Ohio	United States	43235
36	Flower Hospital/ Promedica Health System	Sylvania	Ohio	United States	43560
37	Oregon Urology Institute	Springfield	Oregon	United States	97477
38	Cancer Centre of the Carolinas	Greenville	South Carolina	United States	29605
39	Carolina Urologic Research Center	Myrtle Beach	South Carolina	United States	29572
40	University of Texas Medical Branch	Galveston	Texas	United States	77555-0565
41	The Methodist Hospital	Houston	Texas	United States	77030
42	Urology Associates of South Texas	McAllen	Texas	United States	78503
43	Cancer Outreach Associates PC	Abingdon	Virginia	United States	24211
44	Virginia Oncology Associates	Norfolk	Virginia	United States	23502
45	Seattle Cancer Care Alliance	Seattle	Washington	United States	98109
46	Madigan Army Medical Centre	Tacoma	Washington	United States	98109
47	CHU Besançon Hôpital Minjoz	Besancon		France	25030
48	Centre Francois Baclesse	Caen		France	14076
49	Centre François Baclesse-CLCC-Caen	Caen		France	14076
50	Universitätsklinikum C.G. Carus TU Dresden	Dresden		Germany	01307
51	Oncology department, Assaf Harofeh Medical Center	Be'er Ya'aqov	Zerifin	Israel	70300
52	Oncology institute , Rambam /health Care Campus	Haifa		Israel	31096
53	Meir Medical Center	Kfar Saba		Israel	44281
54	Oncology department Rabin Medical center	Petach Tikva		Israel	49100
55	Tel Aviv Sourasky Medical Center	Tel Aviv		Israel	64239
56	Oncology institute , The Chaim Sheba Medical center	Tel- Hashomer		Israel	52621
57	IIndependent Public Hospital #1- , Oncology and Radiotherapy Dept	Gdańsk		Poland	80-952
58	Holycross Oncology Center in Kielce, Department of Urology	Kielce		Poland	25-734
59	Maria Sklodowska-Curie Memorial Institute, Oncology Center Kraków Clinic Systemic and Generalized Neoplasms	Krakow		Poland	31-115
60	Independent Public Health Care Institution University Hospital in Krakow, Department of Oncology	Kraków		Poland	31-501
61	Lord's Transfiguration Independent Hospital Medical Academy Poznań	Poznan		Poland	61-848
62	Independent Public Clinical Hospital #2 - Pomeranian Medical Academy in Szczecin, Urology Clinic	Szczecin		Poland	70-111
63	Military Institute of Medicine, Department of Oncology	Warsaw,		Poland	00-909
64	Maria Sklodowska-Curie Memorial Institute, Oncology Center in Warsaw, Clinic of Neoplasms of Urinary System	Warsaw		Poland	02-781
65	Regional Specialistic Hospital in Wrocław, Department of Urology	Wrocław		Poland	51-124
66	Private Medical Centre	Arad,		Romania	310175
67	Fundeni Clinical Institute - Urology Department	Bucharest,		Romania	022328
68	Dinu Uromedica	Bucharest,		Romania	041345
69	"Prof. Dr. Th. Burghele" Clinical Hospital, Urology Clinic	Bucharest,		Romania	050659,
70	"Prof. Dr. Th. Burghele" Clinical Hospital, Urology Clinic	Bucharest		Romania
71	E-URO Medical Center	Cluj-Napoca,		Romania	400420
72	"I. Chiricuta" Institute of Oncology	Cluj-Napoca		Romania	400015,
73	Provita Center SRL	Constanţa		Romania	900635
74	Sibiu Clinical County Hospital - Urology Clinic	Sibiu,		Romania	550245
75	Oncomed SRL	Timisoara,		Romania	300239
76	Leningrad Regional Oncological Center, Surgical Department #3	St Petersburg	Leningrad Region	Russian Federation	188663
77	Republican Oncology Center" under the Ministry of Healthcare,	Petrozavodsk	Republic Of Karelia	Russian Federation	185007
78	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	420029
79	State Medical Institution: Arkhangelsk Regional Clinical Oncological Center, Surgery Department 7.	Arkhangelsk		Russian Federation	163045
80	Chelyabinsk Regional Oncological Center, Chemotherapy Department	Chelyabinsk		Russian Federation	454087
81	State Therapeutical and Prophylactic Institution: Chelyabinsk Regional Oncological Center,	Chelyabinsk		Russian Federation	454087
82	Municipal Medical Institution: Oncological Center, Chemotherapy Department	Krasnodar		Russian Federation	350040
83	State Institution: Russian Oncological Research Center n.a. N.N. Blokhin of the Russian Academy of Medical Sciences, Department of Urology	Moscow		Russian Federation	115478
84	Russian Research Center of Roentgenology & Radiology , Surgery Department	Moscow		Russian Federation	117997
85	Russian State Medical University under the Federal Agency for Healthcare and Social Development, Department of Radiology Daignostics and Radiology Therapy	Moscow		Russian Federation	117997
86	Russian State Medical University under the Federal Agency for Healthcare and Social Development, Department of Urology and Surgical Nephrology	Moscow		Russian Federation	117997
87	Moscow Research Oncological Institute n.a. P.A. Hertzen, Urology Departmen	Moscow		Russian Federation	125284
88	Regional Research Clinical Institute n.a M.F. Vladimirskiy, Urology Department #1	Moscow		Russian Federation	129110
89	Non-State Medical Institution:Central Clinical Hospital	Moscow		Russian Federation	129128
90	Murmansk Regional Oncological Center, Oncology Department #5	Murmansk		Russian Federation	183047
91	Privolzhsky County Medical Center	Nizhny Novgorod		Russian Federation	603001
92	State Institution of Nizhny Novgorod Region: "Nizhny Novgorod Oncology Center", Department of Oncology #5 (for chemotherapy treatment)	Nizhny Novgorod		Russian Federation	603081
93	Medical Radiological Research Center under the Russian Academy of Medical Sciences, Department of Urology	Obninsk		Russian Federation	249036
94	State Medical Institution: Omsk Regional Oncological Center, Chemotherapy Department	Omsk		Russian Federation	644013
95	Regional State Medical Institution:"Orel Oncological Center", Oncology Department #5	Orel		Russian Federation	302020
96	Orenburg Regional Clinical Oncological Center, Chemotherapy Department	Orenburg		Russian Federation	460021
97	Pyatigorsk Branch of Stavropol Territorial Clinical Oncological Center (State Medical Institution), Outpatient Department	Pyatigorsk		Russian Federation	357500
98	Rostov State Medical University under the Federal Agency for Healthcare and Social Development, Department of Urology	Rostov-on-Don		Russian Federation	344022
99	Regional Clinical Oncological Center, Surgery Department	Ryazan		Russian Federation	390011
100	Samara Regional Oncology Center, Chemotherapy Department	Samara		Russian Federation	443066
101	"Oncological Center", Department of Haematology and Chemotherapy	Sochi		Russian Federation	354057
102	Municipal Multi-Speciality Hospital #2, Department of Urology	St Petersburg		Russian Federation	194354
103	Municipal Hospital #26, Department Of Urology	St Petersburg		Russian Federation	196247
104	"Central Research Institute of Roentgenology & Radiology Federal Agency Healthcare Social Development"	St Petersburg		Russian Federation	197758
105	Department of Biotherapy and Bone Marrow Transplantation	St Petersburg		Russian Federation	197758
106	St. Petersburg State Pediatric Medical Academy	St. Petersburg		Russian Federation	194100
107	Department of Urology	St. Petersburg		Russian Federation	194291
108	St. Petersburg State Medical Institution: Municipal Hospital #15, Urology Department	St. Petersburg		Russian Federation	198205
109	St. Petersburg State Medical Institution: Municipal Multi-Speciality Hospital #2, Department of Functional Diagnostics	St.Petersburg		Russian Federation	194354
110	State Medical Institution: Stavropol Territorial Clinical Oncological Center, Department of Urology	Stavropol		Russian Federation	355047
111	State Medical Institution: Tambov Regional Oncological Center, Surgery Department	Tambov		Russian Federation	392013
112	State Higher Educational Institution: Siberian State Medical University, Department of Urology	Tomsk, ,		Russian Federation	634050
113	Bashkir State Medical University, Urology Department	Ufa		Russian Federation	634050
114	State Medical Institution of Yaroslavl Region	Yaroslavl		Russian Federation	150054
115	State Institution of Mariy El Republic: "Republican Clinical Hospital", Department Of Urology	Yoshkar-Ola		Russian Federation	424037
116	Hospital Severo Ochoa, Servicio de Oncologia - Primera planta	Leganes	Madrid	Spain	S
117	Hospital de Cruces	Barakaldo		Spain	48903
118	Hospital Santa Creu i Sant Pau Hospital Nuevo-Servicio de Oncologia Medica	Barcelona		Spain	080025
119	Hospital Universitario Ramon y Cajal	Madrid		Spain	28034
120	Hospital Marques de Valdecilla Consultas de Oncologia 1st planta	Santander		Spain	39008
121	Bukovyna State Medical University, Department of Oncology, Radiodiagnostics and Radiotherapy	Chernivtsi		Ukraine	58000,
122	Dnepropetrovsk State Medical Academy, Department of Urology	Dnepropetrovsk		Ukraine	49005
123	Dnepropetrovsk State Medical Academy, Oncology, Radiodiagnostics and Radiotherapy Department	Dnepropetrovsk		Ukraine	49044
124	Donetsk Regional Antitumor Center, Urology Department	Donetsk		Ukraine	83092
125	Ivano-Frankovsk State Medical University; Oncology Department	Ivano-Frankivs'k		Ukraine	76000
126	Kharkov Regional Clinical Urology and Nephrology Center, Oncourology Department	Kharkov		Ukraine	61037
127	Kharkov Medical Academy of Postgraduate Education, Oncology and Pediatric Oncology Department	Kharkov		Ukraine	61176
128	Urology Institute under the Ukrainian Academy of Medical Sciences, Oncourology Department	Kiev		Ukraine	04053
129	Urology Institute under the Ukrainian Academy of Medical Sciences, Plastic and Reconstructive Urology Department	Kiev		Ukraine	04053
130	Regional Public Institution: Krivoy Rog Oncological Center, Chemotherapy Department	Krivoi Rog		Ukraine	50048
131	Lugansk Regional Clinical Oncological Center, Urology Department	Lugansk		Ukraine	91047
132	Crimea State Medical University n.a. S.I. Georgievsky, Course in Urology at the Faculty Surgery#1 Department	Lviv		Ukraine	79010
133	Odessa State Medical University;	Odessa		Ukraine	65074
134	Crimean Republican Clinical Oncological Center, Chemotherapy Department	Simferopol		Ukraine	95023
135	Uzhgorod National University,	Uzhorod		Ukraine	88000
136	Zaporozhye Medical Academy of Postgraduate Education, Oncology Department	Zaporozhye		Ukraine	69096
137	Zaporozhye Medical Academy of Postgraduate Education, Urology Department	Zaporozhye		Ukraine	69600
138	Mount Vernon Cancer Centre	Northwood	Middlesex	United Kingdom	HA6 2RN
139	Belfast City Hospital	Belfast	N. Ireland	United Kingdom
140	Clatterbridge Centre for Oncology	Bebington	Wirral	United Kingdom	CH63 4JY.
141	The Royal Bournemouth Hospital	Bournemouth		United Kingdom	BH7 7DW
142	Bristol Haematology and Oncology Centre	Bristol		United Kingdom	BS2 8ED
143	Beatson Oncology Centre	Glasgow		United Kingdom	G11 6NT
144	St Luke's Cancer Centre, Royal Surrey County Hospital	Guildford		United Kingdom	GU2 7XX
145	St. James University Hospital	Leeds		United Kingdom	LS9 7TF
146	Christie Hospital NHS Trust	Manchester		United Kingdom	M20 4BX
147	The James Cook University Hospital	Middlesbrough		United Kingdom	TS4 3BW
148	University of Nottingham	Nottingham		United Kingdom	NG5 1PB
149	The Churchill Hospital	Oxford		United Kingdom	OX3 7LJ
150	Weston Park Hospital	Sheffield		United Kingdom	S10 2SJ
151	The South West Wales Cancer Institute	Swansea		United Kingdom	SA2 8QA
152	New Cross Hospital	Wolverhampton		United Kingdom	WV10 0QP