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

This is an interventional treatment trial for Ovarian Cancer focused on measuring Randomised, Controlled, Trovax, MVA-5T4, 5T4, Immunotherapy, Relapsed, Asymptomatic, Epithelial, Ovarian, Fallopian, Peritoneal Read More

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