The Activity of TroVax® Versus Placebo in Relapsed Asymptomatic Ovarian Cancer (TRIOC)

Inclusion Criteria:

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

• 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 requirements
• Allergy to egg proteins, neomycin or history of allergic response to vaccinia vaccines
• 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 follow-up