Brief Title
The Activity of TroVax® Versus Placebo in Relapsed Asymptomatic Ovarian Cancer
Official Title
A 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
Brief Summary
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.
Detailed Description
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).
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Progression
Secondary Outcome
Immune-related response criteria (irRC)
Condition
Ovarian Cancer
Intervention
TroVax®
Study Arms / Comparison Groups
TroVax®
Description: 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.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Biological
Estimated Enrollment
94
Start Date
November 2013
Completion Date
April 19, 2019
Primary Completion Date
April 19, 2019
Eligibility Criteria
Inclusion Criteria:
- Aged ≥18 years with histologically or cytologically proven advanced epithelial ovarian
carcinoma, fallopian tube carcinoma or primary peritoneal carcinoma
- Stage IC1 - III or Stage IVA (pleural effusion only) at diagnosis. (According to new
FIGO staging effective 01/01/2014)
- Completed cytoreductive surgery during the phase of first-line therapy including
removal of bulky tumour masses and adequate surgical staging including a minimum of
bilateral salpingo-oophorectomy, hysterectomy and omentectomy
- Completed first line platinum-based chemotherapy OR Completed first line
platinum-based chemotherapy and second line chemotherapy of any type with complete
response to second line treatment according to RECIST 1.1
- Have developed relapse ≥6 months after platinum-based chemotherapy (in the case of
second relapse, the disease free interval should also be ≥6 months)
- Normal CA-125 following platinum-based chemotherapy
- Have developed asymptomatic relapse as defined by:
1. CA125 ≥ 2xULN OR
2. Low volume radiological disease and CA125>ULN Low volume radiological disease is
defined as radiologically visible disease excluding intra-hepatic (parenchymal)
liver or splenic metastases, ascites or pleural effusion thought to require
drainage within the next 2 months. The following are acceptable: Subcapsular
liver and splenic lesions, benign lesions or cysts, any suspicious lesions that
may represent metastases have to be confirmed by further imaging to be
non-metastatic.
- Currently asymptomatic and does not require chemotherapy.
- Subject is assumed to be clinically immunocompetent and is free of clinically
apparent/active autoimmune disease (i.e. no prior confirmed diagnosis or treatment for
autoimmune disease including Systemic Lupus Erythematosis, Grave's disease,
Hashimoto's thyroiditis, multiple sclerosis, and rheumatoid arthritis). Note: subjects
with type I or type II diabetes mellitus can be included, as can subjects with
controlled and rarely flaring rheumatoid disease (defined as recent flare within 6
months prior to randomisation/registration)
- Subject has adequate bone marrow function as defined by Haemoglobin ≥ 110 g/L, white
cell count ≥ 3.0 x 10^9/L, Absolute Lymphocyte Count (ALC) ≥ 1.0 x 10^9/L, Absolute
Neutrophil Count (ANC) ≥1.5 x 10^9/L , Platelet Count ≥ 100 x 10^9/L and <400 x
10^9/L, Monocytes <0.8 x 10^9/L (for patients who have undergone previous splenectomy
monocyte counts can be < 1.2 x 10^9/L)
- Adequate end-organ function: plasma creatinine ≤ 2x upper limit of normal, AST and/or
ALT ≤ 2x upper limit of normal, Total Bilirubin ≤ 1.5x upper limit normal
- ECOG performance status 0-1
- Life expectancy ≥6 months and willing to be available to attend clinic visits for
treatment and for follow-up
- Ability to give written informed consent
- To be treated no later than 14 days from randomisation/registration
Exclusion Criteria:
- Carcino-sarcoma/MMMT
- Cancer related symptoms, or disease recurrence requiring immediate treatment
- Patients with low volume radiological disease in any of the following sites at trial
entry:
- Accumulating ascites thought to require drainage within the next 2 months
- Pleural effusion thought to require drainage within the next 2 months
- Intraparenchymal Liver and/or splenic metastases
- CT scan showing bulky disease requiring chemotherapy, as judged by the investigator
- Major surgery/radiation therapy, immunotherapy or chemotherapy completed < 4 weeks
prior to randomisation/registration
- Patients who are deemed as being immunosuppressed, receiving > 4 weeks parenteral or
oral steroids, (nasal sprays and inhalers are permitted), or receiving
immunosuppressive therapy following transplant
- Chronic (≥ 6 months) oral corticosteroid use except when prescribed as replacement
therapy in the case of adrenal insufficiency. If previously used for ≥6 months then
must have discontinued ≥3 months prior to randomisation/registration.
- "Currently active" second malignancy, other than non-melanoma skin cancer. Subjects
are not considered to have a "currently active" malignancy if they have completed
therapy ≥3 years previously and have no known evidence of residual or recurrent
disease
- Concomitant use of complementary medicines/botanicals. Supplements and conventional
multivitamins are acceptable.
- Evidence of significant clinical disorder or laboratory finding which in the opinion
of the investigator makes it undesirable for the patient to participate in the trial.
No participant should have a serious or uncontrolled intercurrent infection (including
those positive for HIV, hepatitis B or C)
- Psychiatric illnesses/social situations that limit compliance with protocol
requirements
- Allergy to egg proteins or history of allergic response to vaccinia vaccines
- Prior exposure to TroVax®
- Cerebral metastases (known from previous investigations or clinically detectable,
surgically resected)
- Patients on active treatment as part of another clinical trial
Gender
Female
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Agnieszka Michael, MBBS, PhD, ,
Location Countries
United Kingdom
Location Countries
United Kingdom
Administrative Informations
NCT ID
NCT01556841
Organization ID
UCL/11/0119
Responsible Party
Sponsor
Study Sponsor
University College, London
Collaborators
Oxford BioMedica
Study Sponsor
Agnieszka Michael, MBBS, PhD, Principal Investigator, University of Surrey; Royal Surrey County Hospital NHS Foundation Trust
Verification Date
January 2018