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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

Phase 2
18 Years
Not Enrolling
Ovarian Cancer, Fallopian Tube Cancer, Peritoneal Cancer

Thank you

Trial Information

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

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).

Inclusion Criteria:

- Aged ≥18 years with histologically or cytologically proven advanced (stage Ic - III)
epithelial ovarian carcinoma, fallopian tube carcinoma or primary peritoneal

- Completed cytoreductive surgery including removal of bulky tumour masses and adequate
surgical staging including a minimum of bilateral salpingo-ophorectomy, hysterectomy
and abdominal exploration with random peritoneal biopsies, lymph node sampling and
omental biopsy or omentectomy

- Completed first line chemotherapy ≥6 months prior to randomisation and have developed
CA-125 relapse, and are asymptomatic or patients who achieve complete response (CR)
following second line chemotherapy and develop asymptomatic CA-125 relapse

- Had an elevated CA-125 before starting first line chemotherapy with a reduction of at
least 50% by completion of that therapy and complete (CR) or partial response (PR) by
RECIST 1.1 if evaluable disease present on the CT scan. Patients who did not have an
end-of-first line treatment CT scan to document response must have had optimal (less
than 1 cm residual disease) cytoreductive surgery and 6 cycles of chemotherapy with
carboplatin or cisplatin and paclitaxel at standard doses as well as CA-125 response

- 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

- Subject has adequate bone marrow function as defined by Haemoglobin ≥ 11.0 g/dl,
white cell count ≥ 3.0 x 109/L, Absolute Lymphocyte Count (ALC) ≥ 1.0 x 109/L,
Absolute Neutrophil Count (ANC) ≥1.5 x 109/L , Platelet Count ≥ 100 x 109/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

Exclusion Criteria:

- Carcino-sarcoma/MMMT

- CA-125 not previously elevated

- Not completed first line chemotherapy and cytoreductive surgery

- Cancer related symptoms requiring immediate treatment with chemotherapy

- Major surgery/radiation therapy, immunotherapy or chemotherapy completed < 4 weeks
prior to screening

- 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

- "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

- Concomitant use of supplements or complementary medicines/botanicals. The following
exceptions are permitted at screening and during the course of the trial:

- conventional multivitamin supplements

- selenium

- lycopene

- soy supplements

- Vitamin E

- 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

- Allergy to egg proteins, neomycin or history of allergic response to vaccinia

- 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.

- Concurrent chemotherapy, immunotherapy, radiotherapy or investigational agents

- No treatment with bevacizumab

- Prior exposure to TroVax®

- Cerebral metastases (known from previous investigations or clinically detectable,
surgically resected)

- Subject has a Platelet count ≥400 x 109/L; Monocytes ≥0.8 x 109/L

- Women who are lactating

- Patients participating in another clinical trial whether on active treatment or in

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Outcome Measure:


Outcome Description:

RECIST-defined progression

Outcome Time Frame:

At 25 weeks

Safety Issue:


Principal Investigator

Agnieszka Michael, MBBS, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Surrey; Royal Surrey County Hospital NHS Foundation Trust


United Kingdom: Medicines and Healthcare Products Regulatory Agency

Study ID:




Start Date:

October 2012

Completion Date:

October 2018

Related Keywords:

  • Ovarian Cancer
  • Fallopian Tube Cancer
  • Peritoneal Cancer
  • Randomised
  • Controlled
  • Trovax
  • MVA-5T4
  • 5T4
  • Immunotherapy
  • Relapsed
  • Asymptomatic
  • Epithelial
  • Ovarian
  • Fallopian
  • Peritoneal
  • Ovarian Neoplasms
  • Peritoneal Neoplasms
  • Fallopian Tube Neoplasms