A Phase II Trial to Assess TroVax® Plus Chemotherapy in Patients With Malignant Pleural Mesothelioma

NCT ID: NCT01569919

Last Updated: 2013-03-12

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-12-31
• Study Completion Date: 2014-12-31

Brief Summary

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.

Conditions

Malignant; Pleural; Mesothelioma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

TroVax®

In this single-arm study, all participants will receive 9 injections of the TroVax® vaccine, plus standard cisplatin and pemetrexed chemotherapy.

Group Type: EXPERIMENTAL

TroVax®

Intervention Type: BIOLOGICAL

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.

Pemetrexed

Intervention Type: DRUG

500 mg/m\^2 over 10 mins, given on day 3 of weeks 4, 7, 10, 13.

Cisplatin

Intervention Type: DRUG

75mg/m\^2 over 1 hour, given on day 3 of weeks 4, 7, 10, 13

Vitamin B12

Intervention Type: DIETARY_SUPPLEMENT

1000μg intramuscular, Day 2 of weeks 3 and 12

Folic Acid

Intervention Type: DIETARY_SUPPLEMENT

400μg oral daily from Day 2 of week 3 to Day 2 of week 16

Dexamethasone

Intervention Type: DRUG

4mg BD, Days 2-6 of weeks 4, 7, 10, 13

Interventions

TroVax®

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.

Intervention Type: BIOLOGICAL

Pemetrexed

500 mg/m\^2 over 10 mins, given on day 3 of weeks 4, 7, 10, 13.

Intervention Type: DRUG

Cisplatin

75mg/m\^2 over 1 hour, given on day 3 of weeks 4, 7, 10, 13

Intervention Type: DRUG

Vitamin B12

1000μg intramuscular, Day 2 of weeks 3 and 12

Intervention Type: DIETARY_SUPPLEMENT

Folic Acid

400μg oral daily from Day 2 of week 3 to Day 2 of week 16

Intervention Type: DIETARY_SUPPLEMENT

Dexamethasone

4mg BD, Days 2-6 of weeks 4, 7, 10, 13

Intervention Type: DRUG

Eligibility Criteria

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 Cockcroft-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.

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 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Velindre NHS Trust

OTHER_GOV

Sponsor Role: collaborator

June Hancock Mesothelioma Research Fund

UNKNOWN

Sponsor Role: collaborator

Velindre Cancer Centre Stepping Stones Appeal

UNKNOWN

Sponsor Role: collaborator

Wales Cancer Trials Unit

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jason F Lester, FRCR, MRCP

Role: PRINCIPAL_INVESTIGATOR

Velindre Cancer Centre

Locations

Velindre Cancer Centre

Cardiff, South Wales, United Kingdom

Site Status: RECRUITING

Countries

United Kingdom

Central Contacts

Hayley Clements, BSc

Role: CONTACT

skopos@cardiff.ac.uk

+442920687500

Angela Casbard, MSc

Role: CONTACT

skopos@cardiff.ac.uk

+442920687500

Other Identifiers

2010-023230-22

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2010/VCC/0049

Identifier Type: -

Identifier Source: org_study_id