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

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2013 by Wales Cancer Trials Unit
Sponsor:
Collaborators:
Velindre NHS Trust
June Hancock Mesothelioma Research Fund
Velindre Cancer Centre Stepping Stones Appeal
Information provided by (Responsible Party):
Wales Cancer Trials Unit
ClinicalTrials.gov Identifier:
NCT01569919
First received: March 28, 2012
Last updated: March 11, 2013
Last verified: March 2013
  Purpose

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.


Condition Intervention Phase
Malignant
Pleural
Mesothelioma
Biological: TroVax®
Drug: Pemetrexed
Drug: Cisplatin
Dietary Supplement: Vitamin B12
Dietary Supplement: Folic Acid
Drug: Dexamethasone
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Wales Cancer Trials Unit:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 26
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)
Arms Assigned Interventions
Experimental: TroVax®
In this single-arm study, all participants will receive 9 injections of the TroVax® vaccine, plus standard cisplatin and pemetrexed chemotherapy.
Biological: 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.
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, 13
Dietary Supplement: Vitamin B12
1000μg intramuscular, Day 2 of weeks 3 and 12
Dietary Supplement: Folic Acid
400μg oral daily from Day 2 of week 3 to Day 2 of week 16
Drug: Dexamethasone
4mg BD, Days 2-6 of weeks 4, 7, 10, 13

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01569919

Contacts
Contact: Hayley Clements, BSc +442920687500 skopos@cardiff.ac.uk
Contact: Angela Casbard, MSc +442920687500 skopos@cardiff.ac.uk

Locations
United Kingdom
Velindre Cancer Centre Recruiting
Cardiff, South Wales, United Kingdom, CF14 2TL
Sub-Investigator: Mick Button         
Sponsors and Collaborators
Wales Cancer Trials Unit
Velindre NHS Trust
June Hancock Mesothelioma Research Fund
Velindre Cancer Centre Stepping Stones Appeal
Investigators
Principal Investigator: Jason F Lester, FRCR, MRCP Velindre Cancer Centre
  More Information

Additional Information:
No publications provided

Responsible Party: Wales Cancer Trials Unit
ClinicalTrials.gov Identifier: NCT01569919     History of Changes
Other Study ID Numbers: 2010/VCC/0049, 2010-023230-22
Study First Received: March 28, 2012
Last Updated: March 11, 2013
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: Research Ethics Committee

Keywords provided by Wales Cancer Trials Unit:
Phase II
Single arm
Vaccine

Additional relevant MeSH terms:
Mesothelioma
Neoplasms, Mesothelial
Adenoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Pemetrexed
Cisplatin
Dexamethasone
Dexamethasone acetate
Dexamethasone 21-phosphate
BB 1101
Folic Acid
Hydroxocobalamin
Vitamin B Complex
Vitamin B 12
Vitamins
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones

ClinicalTrials.gov processed this record on August 18, 2014