Evaluation of Efficacy, Safety of Vandetanib in Patients With Differentiated Thyroid Cancer

NCT01876784 | Completed Phase 3 Results

• 3 other identifiers: D4203C000112013-000422-58LPS14813
• Study Type: interventional
• Target: 238
• Locations: 12 countries
• Sites: 61

Brief Summary

Primary Objective: To determine the efficacy (as assessed by progression-free survival \[PFS\]) of vandetanib when compared to placebo in participants with differentiated thyroid cancer that is either locally advanced or metastatic who are refractory or unsuitable for radioiodine therapy. Secondary Objectives:

• To determine the efficacy of vandetanib when compared to placebo in this participant population as assessed by efficacy variables including duration of response (DOR), objective response rate (ORR), change in tumour size (TS) and overall survival (OS).
• To evaluate the pharmacokinetics (PK) of vandetanib in this participant population and potentially investigate any influence of participant demography and pathophysiology on vandetanib PK.
• To demonstrate an improvement in time to worsening of pain (TWP) in participants treated with vandetanib when compared to placebo in this participant population.
• To evaluate the safety and tolerability of vandetanib treatment in this participant population.

Conditions

Differentiated Thyroid Cancer

Keywords

vandetanib, AZD 6474, Differentiated Thyroid Cancer

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS)

  The PFS was defined as the time (in months) from randomization until the date of first documented disease progression or death (from any cause), whichever came first. Disease progression as per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) was defined as: at least a 20% increase and absolute increase of 5 mm in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Analysis was performed by Kaplan-Meier method.

  Randomization until disease progression or death, assessed every 12 weeks (up to 22 months)

Secondary Outcomes (6)

• Overall Survival (OS)

  From randomization to the date of death due to any cause (maximum duration: up to 42 months)

• Randomized Treatment Period: Percent Change From Baseline in Tumor Size (TS) at Week 36

  Baseline, Week 36

• Percentage of Participants With Objective Response

  From randomization to the date of first documented tumor progression, or death due to any cause, whichever comes first (maximum duration: up to 42 months)

• Time to Worsening of Pain (TWP) Using Numeric Rating Scale (NRS) of Worst Pain

  From randomization to the date of first assessment of worsening of pain (maximum duration: up to 42 months)

• Duration of Response (DOR)

  From the date of first response to the date of first documented tumor progression or death due to any cause whichever comes first (maximum duration: up to 42 months)

Study Arms (2)

Vandetanib/ Vandetanib

EXPERIMENTAL

Participants received Vandetanib 300 mg tablet, orally once daily until disease progression or death, in randomized treatment period (up to maximum of 40 months). Participants who completed the randomized treatment period, were offered the opportunity to continue the same vandetanib treatment in the open label period, if in the investigator's opinion, they received benefit and if the participant agreed and provided their informed consent to continue the open-label period for up to additional 31 months.

Drug: Vandetanib (SAR390530)

Placebo/ Vandetanib

PLACEBO COMPARATOR

Participants received placebo matched to Vandetanib tablet, orally once daily until disease progression or death, in randomized treatment period (up to maximum of 40 months). Participants who completed the randomized treatment period, and experienced disease progression were offered the option of treatment in open-label period with vandetanib, if in the investigator's opinion, they received benefit and if the participant agreed and provided their informed consent to begin open-label vandetanib treatment i.e., 300 mg tablet, orally once daily for up to 31 months.

Drug: Vandetanib (SAR390530); Drug: Placebo

Interventions

Vandetanib (SAR390530) DRUG

Pharmaceutical form: tablet Route of administration: oral

Also known as: CAPRELSA

Placebo/ Vandetanib; Vandetanib/ Vandetanib

Placebo DRUG

Pharmaceutical form: tablet Route of administration: oral

Placebo/ Vandetanib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of informed consent to participate in the study as well as provision of informed consent to provide a sample of a previously obtained archival tumor biopsy.
• Female or male aged 18 years and older with previously confirmed histological diagnosis of locally advanced or metastatic differentiated (excluding minimally invasive follicular) thyroid cancer not amenable to surgical resection, external beam radiotherapy or local therapy.
• Measurable disease defined as at least one lesion, not irradiated within 12 weeks of the date of randomization, that can be accurately measured at baseline.
• Participants must have experienced progression within 14 months and be RAI-refractory/resistant or unsuitable for RAI.
• Thyroid-stimulating hormone (TSH) suppression below 0.5 mU/L is required.
• World Health Organization (WHO) or Eastern Cooperative Oncology Group (ECOG) Performance status 0-2.
• Negative pregnancy test (urine or serum) for female participants of childbearing potential.

You may not qualify if:

• Inadequate organ function as defined by: (1) Alanine aminotransferase (ALT), aspartate aminotransferase (AST), or alkaline phosphatase (ALP) greater than 2.5\*upper limit of normal (ULN), or greater than 5.0\*ULN if judged by the Investigator to be related to liver metastases. (2) Serum bilirubin greater than 1.5\*ULN. This criterion does not apply to participants with known Gilbert's Disease. (3) Creatinine clearance \<50 mL/min (calculated by Cockcroft-Gault formula).
• Risk of prolonged interval between Q and T (QT) on an electrocardiogram (ECG) corrected for heart rate (QTc) as defined by: (1) Current therapy with any medication known to be associated with Torsades de pointes or potent inducers of cytochrome CYP3A4. (2) History of QT prolongation. (3) Congenital long QT syndrome. (4) QT interval corrected for heart rate by the Bazett's method (QTcB) correction unmeasurable or greater than 480 ms on screening ECG.
• Previous therapy with approved or investigational tyrosine kinase or anti- vascular endothelial growth factor (VEGF) receptor inhibitors or targeted therapies (e.g. multi-targeted kinase inhibitors such as sorafenib, AMG-706, sunitinib, pazopanib, lenvatinib).
• RAI therapy within 12 weeks prior to first dose of study drug, and radiation therapy other than RAI, including external beam, if not completed prior to randomization.

Sponsors & Collaborators

• Genzyme, a Sanofi Company: lead

Study Sites (61)

Research Site

Little Rock, Arkansas, 72205, United States

Location

Research Site

Torrance, California, 90502, United States

Location

Research Site

Lexington, Kentucky, 40536-0293, United States

Location

Research Site

Boston, Massachusetts, 02114, United States

Location

Research Site

Ann Arbor, Michigan, 48109, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Research Site

Omaha, Nebraska, 68198-4100, United States

Location

Research Site

New York, New York, 10065, United States

Location

Research Site

Portland, Oregon, 97239, United States

Location

Research Site

Philadelphia, Pennsylvania, 19014, United States

Location

Research Site

Porto Alegre, Brazil

Location

Research Site

Ribeirão Preto, Brazil

Location

Research Site

Rio de Janeiro, Brazil

Location

Research Site

São José do Rio Preto, Brazil

Location

Research Site

São Paulo, Brazil

Location

Research Site

Beijing, China

Location

Research Site

Changchun, China

Location

Research Site

Chengdu, China

Location

Research Site

Huangzhou, China

Location

Research Site

Shanghai, China

Location

Research Site

Tianjin, China

Location

Research Site

Wuhan, China

Location

Research Site

Olomouc, Czechia

Location

Research Site

Prague, Czechia

Location

Research Site

Odense, Denmark

Location

Research Site

Angers, France

Location

Research Site

Bordeaux, France

Location

Research Site

Caen, France

Location

Research Site

Paris, France

Location

Research Site

Villejuif, France

Location

Research Site

Catania, Italy

Location

Research Site

Milan, Italy

Location

Research Site

Napoli, Italy

Location

Research Site

Pisa, Italy

Location

Research Site

Roma, Italy

Location

Research Site

Siena, Italy

Location

Research Site

Bunkyō City, Japan

Location

Research Site

Fukuoka, Japan

Location

Research Site

Fukushima, Japan

Location

Research Site

Kashiwa-shi, Japan

Location

Research Site

Kobe, Japan

Location

Research Site

Kōtoku, Japan

Location

Research Site

Matsumoto-shi, Japan

Location

Research Site

Nagasaki, Japan

Location

Research Site

Nagoya, Japan

Location

Research Site

Niigata, Japan

Location

Research Site

Osaka, Japan

Location

Research Site

Shinjuku-ku, Japan

Location

Research Site

Yokohama, Japan

Location

Research Site

Gliwice, Poland

Location

Research Site

Kielce, Poland

Location

Research Site

Warsaw, Poland

Location

Research Site

Zgierz, Poland

Location

Research Site

Barnaul, Russia

Location

Research Site

Obninsk, Russia

Location

Research Site

Barcelona, Spain

Location

Research Site

Girona, Spain

Location

Research Site

Hospitalet de Llobregat(Barcel, Spain

Location

Research Site

Madrid, Spain

Location

Research Site

Lund, Sweden

Location

Research Site

Stockholm, Sweden

Location

MeSH Terms

Interventions

vandetanib

Limitations and Caveats

This study was part of the drug acquisition where model-based PK analysis was not performed by the legacy company. Available PK descriptive statistics have been reported.

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi

Contact-US@sanofi.com

800-633-1610

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 11, 2013
• First Posted: June 13, 2013
• Study Start: September 17, 2013
• Primary Completion: August 30, 2015
• Study Completion: January 22, 2022
• Last Updated: July 23, 2024
• Results First Posted: March 13, 2017

Record last verified: 2024-06

Locations

JP (13); RU (2); PL (4); SE (2); DK (1); ES (4); US (10); IT (6); BR (5); CN (7); CZ (2); FR (5)