The Activity of TroVax® Versus Placebo in Relapsed Asymptomatic Ovarian Cancer (TRIOC)
The purpose of this trial is to assess the effectiveness of TroVax® compared to placebo in extending the time to progression in patients with asymptomatic relapsed platinum resistant ovarian, fallopian tube or primary peritoneal cancer.The trial will also look at overall survival times and quality of life.
Fallopian Tube Cancer
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||A Randomised Parallel Group Double-Blind Phase II Study to Assess the Activity of TroVax® (MVA-5T4) Versus Placebo in Patients With Relapsed Asymptomatic Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Cancer|
- Progression [ Time Frame: At 25 weeks ] [ Designated as safety issue: No ]RECIST-defined progression
- Immune-related response criteria (irRC) [ Time Frame: 8 weeks post evidence of progression by RECIST 1.1 ] [ Designated as safety issue: No ]irRC will be used to identify any delayed response.Patients will remain on treatment until irRc has confirmed progression (in the absence of unacceptable toxicity or the need for urgent chemotherapy).
- Progression-free survival [ Time Frame: Time from randomisation to clinical intervention or confirmed evidence of progression or death, assessed for up to 2 years ] [ Designated as safety issue: No ]
- Time to clinical intervention [ Time Frame: Time from randomisation to clinical intervention or death, assessed for up to 2 years ] [ Designated as safety issue: No ]
- Incidence of clinical intervention [ Time Frame: At 25 weeks from randomisation ] [ Designated as safety issue: No ]
- CA-125 doubling time [ Time Frame: Assessed at treatment visits for up to 2 years from randomisation. ] [ Designated as safety issue: No ]To investigate CA-125 doubling time as an independent prognostic factor.
- Overall survival [ Time Frame: Time between randomisation and death assessed for up to 4 years ] [ Designated as safety issue: No ]
- Quality of Life [ Time Frame: For up to 2 years following randomisation or until progression ] [ Designated as safety issue: No ]Patient reported outcome and health-related quality of life measured by standardised questionnaires (EORTC QLQ C-30, EORTC QLQ OV-28)
|Study Start Date:||November 2013|
|Estimated Study Completion Date:||October 2018|
|Estimated Primary Completion Date:||May 2016 (Final data collection date for primary outcome measure)|
TroVax® consists of a highly attenuated VV (Modified Vaccinia Ankara, MVA) containing the human TAA 5T4 under regulatory control of a modified VV promoter, mH5.
Patients will be randomised to receive either TroVax® 1 x 10↑9 TCID50/mL in 1mL (experimental arm) or matched placebo (control arm) on a 1:1 basis. A single dose will be given by intramuscular injection during the following weeks: 2, 4, 7, 10, 13, 19, 25, 31, 37, 43 and 49. No further treatment will be given beyond week 49.Treatment will be stopped early if confirmed progression or unacceptable toxicity.
|Placebo Comparator: Placebo||
Matched placebo will be administered as above.
A significant number of patients with advanced ovarian cancer develop a "CA-125 relapse" without clinical symptoms and with a low volume disease on the CT scan. For this group of patients, no survival benefit has been demonstrated from early chemotherapy treatment and, on average, the time to start of chemotherapy is 5 months. Such patients could benefit from immunotherapy and the time to chemotherapy could potentially be prolonged. Multiple immunotherapy agents, such as anti-CA-125 antibodies and various vaccines, have been tested and, although there is plenty of evidence of immune response, this has not translated to a definitive clinical benefit and is not recommended in clinical practice
5T4 appears to be highly expressed in ovarian cancer and correlates with more advanced stage of disease and poorly differentiated tumours. TroVax®, the vaccine targeting 5T4, has an extensive record of safety and efficacy in humans and vaccination in patients with colorectal, renal, and prostate cancer resulted in immune cellular and humoral responses and signs of clinical benefit.
We propose a trial of TroVax® vaccination in patients with CA-125-relapsed asymptomatic ovarian cancer to assess the clinical efficacy and immunological responses as outlined in this protocol. To allow for capture of any delayed response to immunotherapy, patients who progress on RECIST 1.1 criteria and who do not experience toxicity from treatment will continue on the vaccine/placebo injection until repeat imaging at 8 weeks in order for immune-related response criteria (irRC) to be evaluated in addition to RECIST 1.1 criteria (these patients as a standard of care would not receive any other therapeutic intervention).
|Contact: Laura Stylianou||+44 email@example.com|
|Contact: Yen Ngai||+44 firstname.lastname@example.org|
|East & North Hertfordshire NHS Trust||Not yet recruiting|
|Northwood, Middlesex, United Kingdom, HA6 2RN|
|Principal Investigator: Marcia Hall|
|Leeds Teaching Hospitals NHS Trust||Not yet recruiting|
|Leeds, West Yorkshire, United Kingdom, LS9 7TF|
|Principal Investigator: Geoff Hall|
|The Clatterbridge Cancer Centre NHS Foundation Trust||Recruiting|
|Bebington, Wirral, United Kingdom, CH63 4JY|
|Principal Investigator: Rosie Lord|
|University Hospitals of Bristol NHS Foundation Trust||Not yet recruiting|
|Bristol, United Kingdom, BS2 8ED|
|Principal Investigator: Axel Walther|
|Velindre NHS Trust||Not yet recruiting|
|Cardiff, United Kingdom, CF14 2TL|
|Principal Investigator: Louise Hanna|
|Royal Surrey County Hospital NHS Foundation Trust||Recruiting|
|Guildford, United Kingdom, GU2 7XX|
|Principal Investigator: Agnieszka Michael|
|University College London Hospitals NHS Foundation Trust||Not yet recruiting|
|London, United Kingdom, NW1 2PG|
|Principal Investigator: Rebecca Kristeleit|
|The Christie NHS Foundation Trust||Recruiting|
|Manchester, United Kingdom, M20 4BX|
|Principal Investigator: Andrew Clamp|
|Nottingham University Hospitals NHS Trust||Not yet recruiting|
|Nottingham, United Kingdom, NG5 1PB|
|Principal Investigator: Anjana Anand|
|Oxford University Hospitals NHS Trust||Not yet recruiting|
|Oxford, United Kingdom, OX3 7LE|
|Principal Investigator: Shibani Nicum|
|Plymouth Hospitals NHS Trust||Not yet recruiting|
|Plymouth, United Kingdom, PL6 8OH|
|Principal Investigator: Dennis Yiannakis|
|Principal Investigator:||Agnieszka Michael, MBBS, PhD||University of Surrey; Royal Surrey County Hospital NHS Foundation Trust|