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

NCT01556841 | Completed Phase 2 DMC

• 1 other identifier: UCL/11/0119
• Study Type: interventional
• Target: 94
• Locations: 1 country
• Sites: 12

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.

Conditions

Ovarian Cancer; Fallopian Tube Cancer; Peritoneal Cancer

Keywords

Randomised; Controlled; Trovax; MVA-5T4; 5T4; Immunotherapy; Relapsed; Asymptomatic; Epithelial; Ovarian; Fallopian; Peritoneal

Outcome Measures

Primary Outcomes (1)

• Progression

  Protocol-defined progression

  At 25 weeks

Secondary Outcomes (7)

• Immune-related response criteria (irRC)

  8 weeks post evidence of progression by RECIST 1.1

• Progression-free survival

  Time from randomisation/registration to clinical intervention or confirmed evidence of progression or death, assessed for up to 2 years

• Time to clinical intervention

  Time from randomisation/registration to clinical intervention or death, assessed for up to 2 years

• Incidence of clinical intervention

  At 25 weeks from randomisation/registration

• CA-125 doubling time

  Assessed at treatment visits for up to 2 years from randomisation/registration.

Study Arms (2)

TroVax®

EXPERIMENTAL

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.

Biological: TroVax®

Placebo

PLACEBO COMPARATOR

Biological: Placebo

Interventions

TroVax® BIOLOGICAL

Pre-amendment 10: 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. Post-amendment 10: Patients will be registered to receive TroVax 1 x 10↑9 TCID50/mL in 1mL only. A single dose will be given by intramuscular injection during the following weeks: 2, 4, 7, 10, 13, 19 and 25. No further treatment will be given beyond week 25.Treatment will be stopped early if confirmed progression or unacceptable toxicity.

TroVax®

Placebo BIOLOGICAL

Pre-amendment 10: Matched placebo will be administered as above. Post-amendment 10: TRI-70 onwards received TroVax only.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• CA125 ≥ 2xULN OR
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University College, London: lead
• Oxford BioMedica: collaborator
• Cancer Research UK: collaborator

Study Sites (12)

Leeds Teaching Hospitals NHS Trust

Leeds, West Yorkshire, LS9 7TF, United Kingdom

Location

The Clatterbridge Cancer Centre NHS Foundation Trust

Bebington, Wirral, CH63 4JY, United Kingdom

Location

Brighton and Sussex NHS Foundation Trust

Brighton, BN2 5BE, United Kingdom

Location

University Hospitals of Bristol NHS Foundation Trust

Bristol, BS2 8ED, United Kingdom

Location

Velindre NHS Trust

Cardiff, CF14 2TL, United Kingdom

Location

Beatson West of Scotland Cancer Centre

Glasgow, G12 0YN, United Kingdom

Location

Royal Surrey County Hospital NHS Foundation Trust

Guildford, GU2 7XX, United Kingdom

Location

University College London Hospitals NHS Foundation Trust

London, NW1 2PG, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

Nottingham University Hospitals NHS Trust

Nottingham, NG5 1PB, United Kingdom

Location

Oxford University Hospitals NHS Trust

Oxford, OX3 7LE, United Kingdom

Location

Plymouth Hospitals NHS Trust

Plymouth, PL6 8OH, United Kingdom

Location

Related Publications (1)

• Michael A, Wilson W, Sunshine S, Annels N, Harrop R, Blount D, Pandha H, Lord R, Ngai Y, Nicum S, Stylianou L, Gwyther S, McNeish IA, Hackshaw A, Ledermann J. A randomized phase II trial to examine modified vaccinia Ankara-5T4 vaccine in patients with relapsed asymptomatic ovarian cancer (TRIOC). Int J Gynecol Cancer. 2024 Aug 5;34(8):1225-1231. doi: 10.1136/ijgc-2023-005200.

  PMID: 38760075 DERIVED

Related Links

• Cancer Research UK \& University College London Cancer Trials Centre

MeSH Terms

Conditions

Ovarian Neoplasms; Fallopian Tube Neoplasms; Recurrence

Interventions

TroVax

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Fallopian Tube Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Agnieszka Michael, MBBS, PhD

  University of Surrey; Royal Surrey County Hospital NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 14, 2012
• First Posted: March 16, 2012
• Study Start: November 1, 2013
• Primary Completion: April 19, 2019
• Study Completion: April 19, 2019
• Last Updated: May 9, 2019

Record last verified: 2018-01

Locations

GB (12)