A Phase II Trial to Assess TroVax® Plus Chemotherapy in Patients With Malignant Pleural Mesothelioma (SKOPOS)
This study is for patients with malignant mesothelioma of the lung lining (called pleura) who are planning to have pemetrexed-cisplatin chemotherapy.
We are investigating whether giving a vaccine called TroVax® with pemetrexed-cisplatin chemotherapy is both safe and potentially beneficial in patients with mesothelioma. This vaccine has been used in combination with chemotherapy in other types of cancer and has been shown to be safe. Cancer vaccines work by stimulating the person's immune system to fight the disease, in a similar way to the immune system fighting infection. In laboratory experiments, the vaccine has been shown to stimulate an immune response to a particular protein widely found on mesothelioma cells called 5T4. In patients with mesothelioma it is hoped that the vaccine will stimulate the immune system to attack mesothelioma cells carrying the 5T4 protein.
Pemetrexed-cisplatin chemotherapy is currently seen as the best treatment for patients with mesothelioma, and this is why we plan to combine it with the vaccine. It is hoped that the combination of the TroVax® vaccine and chemotherapy is more beneficial than chemotherapy alone.
Pemetrexed-cisplatin will be given into a vein in the arm (intravenously) every 3 weeks. The TroVax® vaccine will be given as an injection into the shoulder muscle (intramuscularly) 3 weeks before chemotherapy starts, one week before chemotherapy starts, then every 3 weeks. Each participant will receive 4 chemotherapy and 9 vaccine treatments if they complete the planned trial schedule. We aim to recruit 26 patients into the trial over a two year period. If this study shows that pemetrexed-cisplatin chemotherapy plus the TroVax® vaccine is safe and beneficial in terms of stimulating the immune system, the combination will be tested further in larger clinical trials.
Dietary Supplement: Vitamin B12
Dietary Supplement: Folic Acid
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Trial to Assess the Safety, Immunological Activity of TroVax® Plus Pemetrexed/Cisplatin in Patients With Malignant Pleural Mesothelioma|
- Immune response to 5T4 and MVA antigens as measured by intracellular cytokine staining (ICCS) [ Time Frame: 34 weeks ] [ Designated as safety issue: No ]To evaluate whether TroVax® is active in the treatment of MPM. This will be assessed by measuring the cellular or humoral anti-5T4 immune responses following treatment with TroVax® given in combination with Pem/Cis.
- Safety and tolerability [ Time Frame: 34 weeks ] [ Designated as safety issue: Yes ]To investigate the safety and tolerability of TroVax® in combination with Pem/Cis. This will be assessed from toxicity data, SAE reports and dose of chemotherapy received
- Clinical activity in terms of PFS, ORR and OS [ Time Frame: 1 year ] [ Designated as safety issue: No ]To assess secondary measures of clinical activity, including progression-free survival (PFS), objective response rate (ORR), overall survival (OS) at 6 months and 1 year
- Relationship between immune response and clinical response [ Time Frame: 1 year ] [ Designated as safety issue: No ]To explore the relationship between immune response (antibody and cellular responses against the tumour 5T4 and the MVA viral vector) and clinical response (PFS, ORR, OS).
- Identify potential predictors of treatment benefit [ Time Frame: 1 year ] [ Designated as safety issue: No ]To investigate the utility of (a) baseline platelet levels, (b) baseline monocyte levels and (c) baseline haemoglobin as predictors of treatment benefit.
|Study Start Date:||December 2012|
|Estimated Study Completion Date:||December 2014|
|Estimated Primary Completion Date:||June 2014 (Final data collection date for primary outcome measure)|
In this single-arm study, all participants will receive 9 injections of the TroVax® vaccine, plus standard cisplatin and pemetrexed chemotherapy.
Dose of 1 x 10^9 TCID 50/ml, in 1ml, given on day 1 of weeks 1, 3, 6, 9, 12, 15, 18, 21, 24.Drug: Pemetrexed
500 mg/m^2 over 10 mins, given on day 3 of weeks 4, 7, 10, 13.Drug: Cisplatin
75mg/m^2 over 1 hour, given on day 3 of weeks 4, 7, 10, 13Dietary Supplement: Vitamin B12
1000μg intramuscular, Day 2 of weeks 3 and 12Dietary Supplement: Folic Acid
400μg oral daily from Day 2 of week 3 to Day 2 of week 16Drug: Dexamethasone
4mg BD, Days 2-6 of weeks 4, 7, 10, 13
Please refer to this study by its ClinicalTrials.gov identifier: NCT01569919
|Contact: Hayley Clements, BScfirstname.lastname@example.org|
|Contact: Angela Casbard, MScemail@example.com|
|Velindre Cancer Centre||Recruiting|
|Cardiff, South Wales, United Kingdom, CF14 2TL|
|Sub-Investigator: Mick Button|
|Principal Investigator:||Jason F Lester, FRCR, MRCP||Velindre Cancer Centre|