A randomised double blind phase 2 trial of whole brain radiotherapy with or without vandetanib in metastatic melanoma with brain metastases

ISRCTN ISRCTN20253034
DOI https://doi.org/10.1186/ISRCTN20253034
Clinical Trials Information System (CTIS) 2011-000661-12
Protocol serial number 10620
Sponsor Oxford University (UK)
Funder AstraZeneca
Submission date
17/08/2011
Registration date
17/08/2011
Last edited
24/03/2022
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

http://cancerhelp.cancerresearchuk.org/trials/a-trial-looking-radiotherapy-vandetanib-melanoma-spread-brain-radvan

Contact information

Ms Linda Collins
Scientific

Old Road Campus
Roosevelt Drive Headington
Oxford
OX3 7DQ
United Kingdom

Linda.Collins@oncology.ox.ac.uk

Study information

Primary study designInterventional
Study designRandomised; Interventional; Design type: Treatment
Secondary study designRandomised controlled trial
Study type Participant information sheet
Scientific titleA randomised double blind phase 2 trial of whole brain radiotherapy with or without vandetanib in metastatic melanoma with brain metastases
Study acronymRADVAN - XRT +/vandetanib in CNS melanoma
Study objectivesThis 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(s)11/SC/0282
Health condition(s) or problem(s) studiedTopic: National Cancer Research Network; Subtopic: Melanoma; Disease: Melanoma
InterventionEighty 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 typeDrug
PhasePhase II
Drug / device / biological / vaccine name(s)Vandetanib
Primary outcome measure(s)

Efficacy of vandetanib in combination with radiotherapy, compared with radiotherapy; Timepoint(s): Progression free survival in brain (as assessed by MRI scan)

Key secondary outcome measure(s)

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)

Completion date28/11/2014

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexAll
Target sample size at registration86
Key inclusion criteria1. 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
Key exclusion criteria1. 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
Date of first enrolment08/12/2011
Date of final enrolment28/11/2014

Locations

Countries of recruitment

  • United Kingdom
  • England

Study participating centre

Old Road Campus
Oxford
OX3 7DQ
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to shareYes
IPD sharing plan summaryOther
IPD sharing planNot provided at time of registration

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Results article results 01/11/2016 Yes No
HRA research summary 28/06/2023 No No
Participant information sheet Participant information sheet 11/11/2025 11/11/2025 No Yes
Plain English results 24/03/2022 No Yes

Editorial Notes

24/03/2022: Plain English results added.
06/03/2018: Publication reference added.
On 29/02/2016 the overall trial end date was changed from 06/12/2013 to 28/11/2014.

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