Thyroid CancerPhase 2NCT00887107
Sorafenib as Adjuvant to Radioiodine Therapy in Non-Medullary Thyroid Carcinoma
A Phase 2 study testing Sorafenib (nexavar) in people with Thyroid Cancer, run by Leiden University Medical Center at 1 site in Netherlands.
Trial summary
The purpose of this study is to assess whether therapy with Sorafenib reinduces radioiodine uptake in thyroid carcinoma. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Thyroid Cancer
- What is being tested?
- Sorafenib (nexavar)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteNetherlands
- Study dates
- Oct 2007to not given
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- Pregnancy
- Other active malignancies
- Active kidney, liver or pancreatic disease or dysfunction
- Unstable angina pectoris or recent (<3 months) myocardial infarction.
- Coagulopathy
Trial locations and contacts
1 site in 1 country.
About this study
The purpose of this study is to assess whether therapy with Sorafenib reinduces radioiodine uptake in thyroid carcinoma.
Read the 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:
- 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)
- 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).
- 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
- Conditions
- Thyroid Cancer
- Being tested
- Sorafenib (nexavar)
- Medical subject headings
- Thyroid Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sorafenib (nexavar)Drug
Also called nexavar
6 months therapy with Sorafenib 800 mg/day
| Study group | Role | What they receive |
|---|---|---|
| sorafenib | Experimental | 30 patients with non-radioiodine avid differentiated thyroid carcinoma Receives: Drug: Sorafenib (nexavar) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Apr 2009 (estimated)
- Study startOct 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Thyroid CancerStudies of the same condition, open and under way.
- More trials run by Leiden University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Leiden University Medical Center
- Sponsor type
- University, hospital or other
- Investigators
- Johannes W Smit, MD, PhD, Principal investigator, Leiden Universty Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00887107
- Sponsor's protocol ID
- NL17727.058.07
- Other IDs
- P07.109
- Status last verified
- Apr 2009
- First submitted
- 22 Apr 2009
- Last updated
- 23 Apr 2009
- Results posted
- No
- Data monitoring committee
- No
Publications
Abdulrahman RM, Verloop H, Hoftijzer H, Verburg E, Hovens GC, Corssmit EP, Reiners C, Gelderblom H, Pereira AM, Kapiteijn E, Romijn JA, Visser TJ, Smit JW. Sorafenib-induced hypothyroidism is associated with increased type 3 deiodination. J Clin Endocrinol Metab. 2010 Aug;95(8):3758-62. doi: 10.1210/jc.2009-2507. Epub 2010 May 19.
PubMed 20484486Hoftijzer H, Heemstra KA, Morreau H, Stokkel MP, Corssmit EP, Gelderblom H, Weijers K, Pereira AM, Huijberts M, Kapiteijn E, Romijn JA, Smit JW. Beneficial effects of sorafenib on tumor progression, but not on radioiodine uptake, in patients with differentiated thyroid carcinoma. Eur J Endocrinol. 2009 Dec;161(6):923-31. doi: 10.1530/EJE-09-0702. Epub 2009 Sep 22.
PubMed 19773371
Study at a glance
From the registry record, last updated by the sponsor on 23 Apr 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sorafenib as Adjuvant to Radioiodine Therapy in Non-Medullary Thyroid Carcinoma
- ClinicalTrials.gov ID
- NCT00887107
- Acronym / sponsor ID
- NL17727.058.07
- Conditions
- Thyroid Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Leiden University Medical CenterUniversity, hospital or other
- Study start
- Oct 2007
- First posted
- 23 Apr 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to assess whether therapy with Sorafenib reinduces radioiodine uptake in thyroid carcinoma.
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:
- 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)
- 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).
- 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
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| sorafenib | Experimental | Drug: Sorafenib (nexavar)30 patients with non-radioiodine avid differentiated thyroid carcinoma |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (5 listed)
- Pregnancy
- Other active malignancies
- Active kidney, liver or pancreatic disease or dysfunction
- Unstable angina pectoris or recent (<3 months) myocardial infarction.
- Coagulopathy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sorafenib (nexavar)Also: nexavar6 months therapy with Sorafenib 800 mg/day | Drug | sorafenib |
Primary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Apr 2009.
- Derived from this study: PubMed 20484486Abdulrahman RM, Verloop H, Hoftijzer H, Verburg E, Hovens GC, Corssmit EP, Reiners C, Gelderblom H, Pereira AM, Kapiteijn E, Romijn JA, Visser TJ, Smit JW. Sorafenib-induced hypothyroidism is associated with increased type 3 deiodination. J Clin Endocrinol Metab. 2010 Aug;95(8):3758-62. doi: 10.1210/jc.2009-2507. Epub 2010 May 19.
- Derived from this study: PubMed 19773371Hoftijzer H, Heemstra KA, Morreau H, Stokkel MP, Corssmit EP, Gelderblom H, Weijers K, Pereira AM, Huijberts M, Kapiteijn E, Romijn JA, Smit JW. Beneficial effects of sorafenib on tumor progression, but not on radioiodine uptake, in patients with differentiated thyroid carcinoma. Eur J Endocrinol. 2009 Dec;161(6):923-31. doi: 10.1530/EJE-09-0702. Epub 2009 Sep 22.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Johannes W Smit, MD, PhD principal investigator
Leiden Universty Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sorafenib (nexavar) in people with Thyroid Cancer, run by Leiden University Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Apr 2009. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00887107, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Apr 2009.