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 |
| EudraCT/CTIS number | 2011-000661-12 |
| Secondary identifying numbers | 10620 |
- 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
Contact information
Ms Linda Collins
Scientific
Scientific
Old Road Campus
Roosevelt Drive Headington
Oxford
OX3 7DQ
United Kingdom
| Linda.Collins@oncology.ox.ac.uk |
Study information
| Study design | Randomised; Interventional; Design type: Treatment |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| Scientific title | A randomised double blind phase 2 trial of whole brain radiotherapy with or without vandetanib in metastatic melanoma with brain metastases |
| Study acronym | RADVAN - XRT +/vandetanib in CNS melanoma |
| Study objectives | 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(s) | 11/SC/0282 |
| Health condition(s) or problem(s) studied | 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 |
| Pharmaceutical study type(s) | |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | 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 study start date | 08/12/2011 |
| Completion date | 28/11/2014 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 86; UK Sample Size: 86 |
| Key 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 |
| Key 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 |
| Date of first enrolment | 08/12/2011 |
| Date of final enrolment | 28/11/2014 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
Old Road Campus
Oxford
OX3 7DQ
United Kingdom
OX3 7DQ
United Kingdom
Sponsor information
Oxford University (UK)
University/education
University/education
Wellcome Trust Centre for Human Genetics
Oxford
OX3 7BN
England
United Kingdom
"ROR" |
https://ror.org/052gg0110 |
|---|
Funders
Funder type
Industry
AstraZeneca
Government organisation / For-profit companies (industry)
Government organisation / For-profit companies (industry)
- Alternative name(s)
- AstraZeneca PLC, Pearl Therapeutics
- Location
- United Kingdom
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Other |
| Publication and dissemination plan | To be confirmed at a later date |
| IPD sharing plan | Not 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 | |
| Plain English results | 24/03/2022 | No | Yes | ||
| HRA research summary | 28/06/2023 | No | No |
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.
