Systemic Treatment of Resistant Metastatic Disease
Non-small Cell Lung Cancer - Castrate-resistant Prostate Cancer - Melanoma - Bladder Cancer
Conditions: official terms
Carcinoma, Non-Small-Cell Lung - Prostatic Neoplasms - Urinary Bladder Neoplasms
Study Type
Study Phase
Phase 1
Study Design
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Name: CVA21
Type: Biological
Overall Status
This study will consist of 2 sequential parts: the first part (VLA009A)is a study of intravenous CVA21 as a single agent for the treatment of 4 different advanced solid tumours; the second part (VLA009B) is a study of intravenous CVA21 in combination with cytotoxic therapy appropriate for the solid tumour selected in the first part. Both parts will be open-label, multi-centre, ascending dose escalation (3+3 design) dose-finding and signal seeking studies.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 18 Years
Gender: Both
Criteria: Inclusion Criteria:

- Histologically-confirmed (1) NSCLC, (2) bladder cancer, (3) castrate-resistant prostate cancer which are metastatic, or (4) stage 3C or stage 4 melanoma.

- VLA009A: Locally advanced and/or metastatic disease for which curative surgery and/or radiation therapy is not possible and judged not to be a candidate for the current standard of care treatment. VLA009B: locally advanced and/or metastatic disease and judged to be a candidate for the selected cytotoxic therapy to be used in combination with CVA21.

- Patients with metastatic CRPC must have progressive disease despite surgical castration or ongoing use of gonadotropin-releasing hormone agonists with confirmed castrate levels of testosterone.

- All subjects in Cohort 3 or Phase 2 dose (P2D) must have a lesion accessible for FNA or core or open biopsy on day 8 of the first treatment cycle.

- No CVA21 neutralising antibody (≤ 1:16)

- ECOG score 0-2

- Life expectancy > 3 months

- Acceptable haematological, renal and hepatic function

- Protocol approved by local Research Ethics Committees

- No chemotherapy, radiation therapy, hormonal treatment of immunotherapy within 28 days of dosing (except active ongoing hormonal therapy for CRPC)

- Patients must give informed written consent

- Women of childbearing potential must have negative pregnancy test

- Measurable or evaluable disease

Exclusion Criteria:

- Active cardiac disease

- Women who are pregnant or lactating

- HIV, hepatitis B or C infections

- Serious neurologic or psychiatric disease

- Second primary malignancy within the past 2 years (except non-melanoma skin cancer, in situ carcinoma of the cervix, breast cancer)

- Active uncontrolled infection

- Concurrent immunosuppressive therapy and no known immunosuppressive disease other than primary tumour

- Residual effects from previous therapy that has not resolved to grade 1 or less

- VLA009B: no medical contraindications to planned cytotoxic therapy
St James University Hospital
Leeds, United Kingdom
Status: Recruiting
Contact: Christy Ralph
Institute of Cancer Research
London, United Kingdom
Status: Recruiting
Contact: Kevin Harrington
University of Surrey
Surrey, United Kingdom
Status: Recruiting
Contact: Hardev Pandha
Start Date
January 2014
Record processing date processed this data on July 28, 2015 page