Condition category
Cancer
Date applied
17/08/2011
Date assigned
17/08/2011
Last edited
29/02/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

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 measures

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

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

Sponsor information

Organisation

Oxford University (UK)

Sponsor details

Wellcome Trust Centre for Human Genetics
Oxford
OX3 7BN
United Kingdom

Sponsor type

University/education

Website

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

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

On 29/02/2016 the overall trial end date was changed from 06/12/2013 to 28/11/2014.