European, Observational, Prospective Study to Evaluate the Benefit/Risk of Vandetanib (CAPRELSA™) 300 mg in RET Mutation Negative and RET Mutation Positive Patients with Symptomatic, Aggressive, Sporadic, Unresectable, Locally Advanced/Metastatic Medullary Thyroid Cancer (MTC)

Study Objective

1. To determine the Objective Response Rate (ORR) for patients treated with vandetanib who are RET mutation positive and patients treated with vandetanib who are RET mutation negative

2. To determine the Disease Control Rate (DCR) for patients treated with vandetanib who are RET mutation positive and patients treated with vandetanib who are RET mutation negative

3. To assess the duration of response and time to response for patients treated with vandetanib who are RET mutation positive and patients treated with vandetanib who are RET mutation negative

4. To explore the clinical outcomes (including but not limited to PFS and ORR) amongst RET mutation negative patients not treated with vandetanib

5. To evaluate the incidence of QTc prolongation and associated risks for QTc prolongation in patients receiving vandetanib who are RET mutation positive and RET mutation negative. In addition, the incidence of SAEs and AEs leading to discontinuation of vandetanib will be assessed.

6. To compare Progression-Free Survival (PFS) for patients treated with vandetanib who are RET mutation positive to patients treated with vandetanib who are RET mutation negative

Participation conditions

Inclusion criteria

• Male or female aged 18 years or above
• Histological diagnosis of MTC
• Patients with symptomatic and aggressive sporadic MTC, who have unresectable, locally advanced/metastatic disease. Measurable disease:
  • assessment confirmed within the 12 weeks previous to start of treatment, and
  • defined according to RECIST 1.1: at least one lesion, not irradiated, that can be accurately measured as ≥10 mm in the longest diameter (except lymph nodes which must have short axis ≥15 mm) with CT or MRI and which is suitable for accurate repeated measurements. Measurable lesions with calcifications should not be assessed as target lesions unless no other measurable lesion is available.
• Known definite RET mutation status. The status should be:
  • for patients prescribed with vandetanib: positive or negative
  • for patients not prescribed with vandetanib: negative.
• For patients newly prescribed vandetanib 300 mg, the prescription should be issued according to marketing authorisation and following the vandetanib Summary of Product Characteristics (SmPC). The starting dose could be reduced to 200 mg in patients with moderate renal impairment

Exclusion criteria

• Current or planned inclusion/participation in a clinical trial
• Patients already receiving vandetanib or who have received vandetanib for their MTC before the study first visit
• Contraindications according to the vandetanib SmPC (not applicable for patients who do not receive vandetanib):
  • Patients with a QT interval corrected for heart rate (QTc) interval over 480 msec: - Congenital long QT syndrome
• Concomitant use of vandetanib with the following medicinal products known to also prolong the QT interval and / or induce Torsades de pointes: Arsenic, cisapride, erythromycine intravenous (IV), toremifene, mizolastine, moxifloxacine, Class IA and III antiarrhythmics
• Currently pregnant or breast feeding
• Hypersensitivity to the active substance or to any of the excipients
• Severe renal impairment: creatinine clearance < 30 ml/minute calculated by Cockcroft-Gault formula.
• Serum bilirubin greater than 1.5 x the upper limit of reference range (ULRR)
• Potassium, magnesium or calcium outside the normal laboratory range

Centre Hospitalier du Luxembourg (CHL)