Plain English Summary
Trial website
Contact information
Type
Scientific
Primary contact
Ms Linda Collins
ORCID ID
Contact details
Old Road Campus
Roosevelt Drive Headington
Oxford
OX3 7DQ
United Kingdom
-
Linda.Collins@oncology.ox.ac.uk
Additional identifiers
EudraCT number
2011-000661-12
ClinicalTrials.gov number
Protocol/serial number
10620
Study information
Scientific title
A randomised double blind phase 2 trial of whole brain radiotherapy with or without vandetanib in metastatic melanoma with brain metastases
Acronym
RADVAN - XRT +/vandetanib in CNS melanoma
Study hypothesis
This is a randomised, double-blind, placebo-controlled, multi-centre phase 2 trial. Eighty patients (forty in each of two arms) will be randomised 1:1 between radiotherapy with placebo or radiotherapy with vandetanib, with stratification for recursive partitioning analysis (RPA) score (2 levels, RPA 1 and RPA 2). Patients will receive three weeks of either vandetanib 100mg once daily or placebo, starting 4 days (+/- 1 day) before whole brain radiotherapy (30 Gy in 10 fractions). The main study will be preceded by a safety run in phase (involving 6 patients) to confirm the tolerability of vandetanib 100mg with radiotherapy at 30 Gy in 10 fractions in this patient group. Tolerability will be defined as no study treatment related toxicity of grade 3 or more (CTCAE version 4.0) in at least 5 out of the 6 patients in the safety run in phase at 30 days post end of study treatment. Patients will continue to be reviewed on study until progression of brain metastases (by RECIST version 1.1) or 12 months post randomisation into study, whichever comes first, and thereafter will be followed up for survival alone.
Ethics approval
11/SC/0282
Study design
Randomised; Interventional; Design type: Treatment
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Topic: National Cancer Research Network; Subtopic: Melanoma; Disease: Melanoma
Intervention
Eighty patients (forty in each of two arms) will be randomised 1:1 between radiotherapy with placebo or radiotherapy with vandetanib, with stratification for RPA score (2 levels, RPA 1 and RPA 2). The main study will be preceded by a safety run in phase involving 6 patients on radiotherapy with vandetanib.
Radiotherapy will be administered via parallel opposed lateral beams dosed to the midpoint as 30 Gy in 10 fractions over 2 weeks (i.e. over 10-14 days, to allow for weekends), starting 4 days (+/- 1 day) after commencing study drug.
Vandetanib/Placebo: Patients in the safety run-in phase will all receive vandetanib 100 mg OD, starting 4 days (+/- 1 day) before whole brain radiotherapy (WBRT) and continuing for 21 days in total. Patients in the randomisation phase will receive vandetanib/placebo, starting 4 days (+/- 1 day) before WBRT and continuing for 21 days in total. No study treatment is to be given beyond day 21, even if any doses are missed during this period.
Intervention type
Drug
Phase
Phase II
Drug names
Vandetanib
Primary outcome measure
Efficacy of vandetanib in combination with radiotherapy, compared with radiotherapy; Timepoint(s): Progression free survival in brain (as assessed by MRI scan)
Secondary outcome measures
1. Safety and tolerability of vandetanib in combination with radiotherapy; Timepoint(s): Adverse events using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0
2. Vital signs and weight
3. Biochemistry, haematology
4. Efficacy of vandetanib in combination with radiotherapy, compared with radiotherapy; Timepoint(s): Maintenance of cognitive function (as assessed by Wide Range Achievement Test)
Overall trial start date
08/12/2011
Overall trial end date
28/11/2014
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. More than or equal to 18 years of age, written informed consent
2. Histological confirmation of malignant melanoma
3. Unresectable Stage III or IV metastatic melanoma with brain metastases
4. Karnofsky Performance Score > 70%
5. Radiation Therapy Oncology Group recursive partitioning analysis (RTOG RPA) score 1 or 2
6. Measurable disease as defined by RECIST version 1.1
7. Adequate haematological, hepatic and renal function
8. Adequate cardiac function New York Heart Association (NHYA) 0-1
9. QTc < 480msec
Target Gender: Male & Female ; Lower Age Limit 18 years
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
Planned Sample Size: 86; UK Sample Size: 86
Participant exclusion criteria
1. Radiotherapy or systemic melanoma therapy within 28 days prior to starting treatment
2. Prior whole brain irradiation
3. Central nervous system (CNS) melanoma where all detectable disease has been treated by neurosurgery or stereotactic irradiation
4. Presence of leptomeningeal disease
5. More than 3 extra-cranial organ sites involved with melanoma
6. Pregnancy or breastfeeding women
7. Significant cardiovascular disease
8. Uncontrolled hypertension
9. Serum calcium, magnesium or potassium below the normal range despite supplementation
10. Requirement for medication that increases QTc and/or the risk of torsades de point
11. Requirement for medication that is a potent inducer of CYP3A4 function
12. Ocular malignant melanoma
13. Another active malignancy within the past five years
14. Clinically significant and uncontrolled major medical condition(s)
15. Any condition that would preclude adequate absorption of vandetanib
Recruitment start date
08/12/2011
Recruitment end date
28/11/2014
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Old Road Campus
Oxford
OX3 7DQ
United Kingdom
Funders
Funder type
Industry
Funder name
AstraZeneca
Alternative name(s)
Funding Body Type
private sector organisation
Funding Body Subtype
corporate
Location
United Kingdom
Results and Publications
Publication and dissemination plan
To be confirmed at a later date
Intention to publish date
Participant level data
Other
Basic results (scientific)
Publication list
2016 results in https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5104891/