Observational Study to Evaluate Vandetanib in RET -/+ Patients With Metastatic Medullary Thyroid Cancer (Caprelsa104)

• ClinicalTrials.gov Identifier: NCT01945762
• Recruitment Status: Completed
• First Posted: September 19, 2013
• Last Update Posted: October 19, 2020
• Sponsor: Genzyme, a Sanofi Company
• Collaborator: Worldwide Clinical Trials
• Information provided by (Responsible Party): Sanofi ( Genzyme, a Sanofi Company )

Study Description

Brief Summary:

This is a European multinational, multicenter, non-interventional (observational) and prospective study. It is carried on to confirm in real life conditions the benefit/risk of vandetanib (CAPRELSA™) 300 mg, both in RET negative and RET positive patients with symptomatic, aggressive, sporadic, unresectable, locally advanced/metastatic MTC.

Condition or disease	Intervention/treatment
Symptomatic, Aggressive, Sporadic, Unresectable, Locally; Advanced/Metastatic Medullary Thyroid Cancer (MTC)	Drug: Vandetanib 300 mg

Detailed Description:

This is a multinational, multicenter, non-interventional (observational) and prospective study. European countries where vandetanib is on the market will participate in the study.

This study is being conducted to fulfil the specific obligation post-authorisation measure for the conditional marketing authorisation. It is carried on to confirm in real life conditions the benefit/risk of vandetanib (CAPRELSA™) 300 mg, both in RET negative and RET positive patients with symptomatic, aggressive, sporadic, unresectable, locally advanced/metastatic MTC. The clinical benefit of vandetanib (CAPRELSA™) 300 mg has previously been established in a clinical trial (Study 58) on the basis of a clinically and statistically significant advantage in progression free survival (PFS) which was supported by a high response rate and substantial duration of response.

Study Design

• Study Type: Observational
• Actual Enrollment: 31 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: European, Observational, Prospective Study to Evaluate the Benefit/Risk of Vandetanib in RET Mutation Negative and Positive Patients With Symptomatic, Aggressive, Sporadic, Unresectable, Locally Advanced/Metastatic Medullary Thyroid Cancer
• Actual Study Start Date: February 17, 2014
• Actual Primary Completion Date: June 18, 2020
• Actual Study Completion Date: June 18, 2020

Groups and Cohorts

Group/Cohort	Intervention/treatment
1. patient cohorts (40 patients/cohort); RET positive patient cohorts	Drug: Vandetanib 300 mg; Vandetanib commercial tablets; Other Name: ZD6474, CAPRELSA
2. patient cohorts (40 patients/cohort); RET negative patient cohorts	Drug: Vandetanib 300 mg; Vandetanib commercial tablets; Other Name: ZD6474, CAPRELSA

Outcome Measures

Primary Outcome Measures :

1. Assessment of Objective Response Rate [ Time Frame: From enrollment until study completion, assessed up to 38 months ]
   Assessment of Objective Response Rate [using Response Evaluation Criteria In Solid Tumours (RECIST) 1.1]
2. Assessment of Disease control rate [ Time Frame: From enrollment until study completion, assessed up to 38 months ]
   Assessment of Disease control rate [using Response Evaluation Criteria In Solid Tumours (RECIST) 1.1]
3. Assessment of Duration of Response [ Time Frame: From enrollment until study completion, assessed up to 38 months ]
   Assessment of Duration of Response (using RECIST 1.1)
4. Assessment of Progression Free Survival [ Time Frame: From enrollment until study completion, assessed up to 38 months ]
   Assessment of Progression Free Survival (using RECIST 1.1)
5. Evaluation of Safety by assessment of QTc prolongations [ Time Frame: From enrollment until study completion, assessed up to 38 months ]
   Assessment of QTc prolongations
6. Evaluation of Safety by assessment of Adverse Events [ Time Frame: From enrollment until study completion, assessed up to 38 months ]
   Assessment of Adverse Events
7. Evaluation of Safety by assessment of vital signs [ Time Frame: From enrollment until study completion, assessed up to 38 months ]
   Assessment of Vital signs
8. Evaluation of Safety by assessment of laboratory data [ Time Frame: From enrollment until study completion, assessed up to 38 months ]
   Assessment of Laboratory data

Secondary Outcome Measures :

1. Patient Characteristics [ Time Frame: From enrollment until study completion, assessed up to 38 months ]
   Patient demographics and medical history / Disease characteristics / Death / Treatment information

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 99 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Patients with Symptomatic, Aggressive, Sporadic, Unresectable, Locally Advanced/Metastatic Medullary Thyroid Cancer (MTC)

Criteria

Inclusion Criteria:

1. Signed informed consent 2. Male or female aged 18 years or above 3. Histological diagnosis of MTC 4. Patients with symptomatic and aggressive sporadic MTC, who have unresectable, locally advanced/metastatic disease. (The factors considered by the investigator to determine a patient's disease to be symptomatic and aggressive will be recorded in the CRF). 5. 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. 6. Known definite RET mutation status (definition according to section 3.2). The status should be:
• for patients prescribed with vandetanib: positive or negative

• for patients not prescribed with vandetanib: negative RET mutation status must be determined from a tumour sample obtained within 18 months prior to enrollment. It is strongly recommended that a tissue sample obtained within 6 months prior to enrolment is used. 7. 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) (Appendix B). The starting dose could be reduced to 200 mg in patients with moderate renal impairment

  • Exclusion criteria

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

Contacts and Locations

Locations

Belgium

investigational Site Belgium

Belgium, Belgium

France

investigational Site France

France, France

Germany

investigational Site Germany

Germany, Germany

Italy

investigational Site Italy

Italy, Italy

Luxembourg

investigational Site Luxembourg

Luxembourg, Luxembourg

Netherlands

investigational Site Netherlands

Netherlands, Netherlands

Spain

investigational Site Spain

Spain, Spain

United Kingdom

investigational Site United Kingdom

United Kingdom, United Kingdom

Sponsors and Collaborators

Genzyme, a Sanofi Company

Worldwide Clinical Trials

Investigators

• Study Director: Clinical Sciences & Operations; Sanofi

More Information

• Responsible Party: Genzyme, a Sanofi Company
• ClinicalTrials.gov Identifier: NCT01945762
• Other Study ID Numbers: D4200C00104; OBS14778 ( Other Identifier: Sanofi )
• First Posted: September 19, 2013
• Last Update Posted: October 19, 2020
• Last Verified: October 2020

Keywords provided by Sanofi ( Genzyme, a Sanofi Company ):

RET Mutation; DIagnostics; Medullary Thyroid Cancer; MTC

Additional relevant MeSH terms:

Thyroid Neoplasms; Carcinoma, Neuroendocrine; Thyroid Diseases; Aggression; Endocrine System Diseases; Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Behavioral Symptoms; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue