E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
The study is for patients with malignant mesothelioma of the lung lining(called pleura). |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 13.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10035603 |
E.1.2 | Term | Pleural mesothelioma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
|
E.2.2 | Secondary objectives of the trial |
To investigate the safety and tolerability of TroVax® in combination with Pem/Cis To assess secondary measures of clinical efficacy, including progression-free survival (PFS), objective response rate (ORR), overall survival (OS) at 6 months and 1 year. 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). To investigate the utility of (a) baseline platelet levels, (b) baseline monocyte levels and (c) baseline haemoglobin as predictors of treatment benefit. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Signed and dated written informed consent obtained from the patient in accordance with the local regulations • Locally advanced or metastatic, histologically or cytologically proven MPM • Aged 18 years or over • WHO performance status 0-1 (Appendix I) • Life expectancy > 6months • Haemoglobin ≥ 12 g/dl, total white cell count ≥ 3 x 10^9/L, neutrophil count > 1.5 x 10^9/L, lymphocyte count ≥1 x 10^9/L, monocyte count <0.8 x 10^9/L platelet count >100 x 10^9/L and <400 x 10^9/L. Blood transfusion is allowed. • Adequate renal function: Creatinine ≥ 50 mL/min as measured by EDTA or 60mL/min as measured by the Cockroft-Gault formula • Adequate liver function: ALT, AST and bilirubin < 2 times the upper limit of normal • At least four weeks from any previous therapy including surgery, or radiotherapy • Able to comply with the protocol • Women must be either post-menopausal, or rendered surgically sterile or, if of child-bearing potential, must have a negative pregnancy test prior to trial entry. Two reliable forms of contraception (oral contraception and a barrier method) must be used by all participants while they are being treated with the TroVax® vaccine. Females must continue to use this level of contraception for 3 months following the last trial treatment, and male patients must continue for 1 month. |
|
E.4 | Principal exclusion criteria |
*Serious infections within the 28 days prior to entry to the trial. *Prior TroVax® treatment *Previous chemotherapy for MPM *Major surgery or radiation therapy completed ≤ 4 weeks prior to enrolment *Prior radiopharmaceuticals (strontium, samarium) less than 8 weeks prior to enrolment *Participation in any other clinical trial of a licensed or unlicensed drug within the previous 30 days *History of prior malignant disease unless patient has been disease-free for at least 3 years or the tumour was a non-melanoma skin cancer or early cervical cancer *Autoimmune disease including systemic Lupus Erythematosis, Grave’s disease, Hashimoto’s thyroiditis, multiple sclerosis, insulin dependent diabetes mellitus or systemic (non-joint) manifestations of rheumatoid disease *Clinical significant cardiac failure or a measured ejection fraction of <40% *Other severe acute or chronic medical or psychiatric conditions or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgement of the investigator, would make the patient inappropriate for entry into this study. *Chronic oral corticosteroid use unless prescribed as replacement therapy in the case of adrenal insufficiency, or other immunosuppressive agents. Dexamethasone is allowed as part of trial treatment. *Cerebral metastases *History of allergic response to previous vaccine vaccinations *Known allergy to egg proteins *Known to test positive for HIV or hepatitis B or C *Pregnancy or lactation *Prior history of organ transplantation |
|
E.5 End points |
E.5.1 | Primary end point(s) |
*Cellular response to 5T4 and MVA antigens as measured by Peripheral Blood Mononuclear Cell (ICCS) *Antibody response to 5T4 and MVA antigens as measured by ELISA |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
The study end date is deemed to be the date of last data capture, (last participant, last visit). |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |