Sorafenib as Adjuvant to Radioiodine Therapy in Non-Medullary Thyroid Carcinoma

This study has been completed.
Sponsor:
Information provided by:
Leiden University Medical Center
ClinicalTrials.gov Identifier:
NCT00887107
First received: April 22, 2009
Last updated: NA
Last verified: April 2009
History: No changes posted
  Purpose

The purpose of this study is to assess whether therapy with Sorafenib reinduces radioiodine uptake in thyroid carcinoma.


Condition Intervention Phase
Thyroid Cancer
Drug: Sorafenib (nexavar)
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Sorafenib as Adjuvant to Radioiodine Therapy in Non-Medullary Thyroid Carcinoma

Resource links provided by NLM:


Further study details as provided by Leiden University Medical Center:

Primary Outcome Measures:
  • Proportion of patients with a favorable response to Sorafenib defined as ONE OR MORE of the following criteria: 1. Reinduction of RaI uptake by RaI scintigraphy. 2. Serum thyroglobulin levels. 3. RECIST criteria [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Enrollment: 32
Study Start Date: October 2007
Arms Assigned Interventions
Experimental: sorafenib
30 patients with non-radioiodine avid differentiated thyroid carcinoma
Drug: Sorafenib (nexavar)
6 months therapy with Sorafenib 800 mg/day
Other Name: nexavar

  Hide Detailed Description

Detailed Description:

Background of the study:

Therapy with radioiodine (RaI) is the only curative therapy in non-medullary thyroid carcinoma. RaI uptake is frequently lost in this disease. Therapy with tyrosine kinase inhibitors may restore the susceptibility to RaI.

Objective of the study:

To investigate whether therapy with the tyrosine kinase inhibitor Sorafenib will increase the accumulation of radioiodine (RaI) and decrease tumor progression in patients with recurrences or metastases of non-medullary thyroid carcinoma with absent or insufficient accumulation of RaI.

Study design:

Prospective, open study with patients with recurrences or metastases of differentiated thyroid carcinoma who will undergo 6 months therapy with Sorafenib 800 mg/day. Patients in whom RaI uptake will be restored will be offered high dose (6000 MBq) RaI together with an additional 6 months treatment with Sorafenib. Patients in whom RaI is not be restored but in whom Sorafenib had a favorable effect on tumor growth will be offered continued treatment with Sorafenib.

Study population:

Thirty patients will be included with recurrences or metastases of differentiated thyroid carcinoma that are unresponsive to RaI therapy.

Intervention (if applicable):

After inclusion, patients will undergo 131I scintigraphy as well as a CT scan. Thereafter, therapy with Sorafenib 800 mg/day will be initiated, and continued during 6 months. After 6 months, 131I scintigraphy and CT scans will be repeated. Serum levels of thyroglobulin will be used as tumormarker.

Primary study parameters/outcome of the study:

The endpoint of the study is the proportion of patients with a favorable response to Sorafenib defined as ONE OR MORE of the following criteria:

  1. Reinduction of RaI uptake by RaI scintigraphy: The appearance of one or more RaI accumulating lesions at RaI scintigraphy, planar images and/or SPECT (see below)
  2. Serum thyroglobulin levels:

    The absence of progression: no statistically significant positive slope at linear regression of the log-transformed serum Tg levels, measured at 0, 4, 8, 12, 16, 20, 24 and 28 weeks after start of Sorafenib:

    • Stable disease: The slope at linear regression of the log-transformed serum Tg levels, measured at 0, 4, 8, 12, 16, 20, 24 and 28 weeks after start of Sorafenib is not significantly different from 0 ln ug/L*time OR
    • Response: The slope at linear regression of the log-transformed serum Tg levels is negative (statistically significantly below 0 ln ug/L*time).
  3. CT Imaging:

The absence of progression according to RECIST criteria:

  • Stable disease—neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum longest diameter since the treatment started.
  • Partial response—at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter;
  • Complete response: the disappearance of all target lesions
  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with non-medullary thyroid carcinoma
  • The patients must have undergone total thyroidectomy
  • Presence of metastases or inoperable recurrent disease, as proven by elevated serum thyroglobulin levels (Tg) in combination with radiological evidence for tumor
  • No or insufficient RaI uptake in tumor as proven by RaI scintigraphy, performed after prior RaI therapy

Exclusion Criteria:

  • Pregnancy
  • Other active malignancies
  • Active kidney, liver or pancreatic disease or dysfunction
  • Unstable angina pectoris or recent (<3 months) myocardial infarction.
  • Coagulopathy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00887107

Locations
Netherlands
Leiden University Medical Center
Leiden, Netherlands, 2300 RC
Sponsors and Collaborators
Leiden University Medical Center
Investigators
Principal Investigator: Johannes W Smit, MD, PhD Leiden Universty Medical Center
  More Information

No publications provided by Leiden University Medical Center

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Johannes Smit, M.D., Ph.D., leiden University Medical Center
ClinicalTrials.gov Identifier: NCT00887107     History of Changes
Other Study ID Numbers: NL17727.058.07, P07.109
Study First Received: April 22, 2009
Last Updated: April 22, 2009
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Additional relevant MeSH terms:
Thyroid Diseases
Thyroid Neoplasms
Carcinoma
Endocrine System Diseases
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Head and Neck Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Sorafenib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 30, 2014