Differentiated Thyroid CancerPhase 3NCT03048877
Efficacy of Apatinib in Radioactive Iodine-refractory Differentiated Thyroid Cancer
A Phase 3 study testing Apatinib Oral Tablet in people with Differentiated Thyroid Cancer, run by Peking Union Medical College Hospital at 2 sites in China.
Trial summary
Radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC) is a great challenge in the treatment of thyroid cancer. Tyrosine kinase inhibitors (TKIs), like sorafenib and lenvatinib which have been approved by food and drug administration (FDA), could not be affordable for most of the Chinese patients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Differentiated Thyroid Cancer
- What is being tested?
- Apatinib Oral Tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 118 participants
- Where
- 2 sitesChina
- Study dates
- Dec 2016to 31 Dec 2023
- Phase
- Phase 3
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Aged after 18 years (18 is included).
- Locally advanced or metastatic differentiated thyroid cancer (papillary, follicular, Hurthle cells, poorly differentiated carcinoma). At least one measurable lesion (helical CT scan long diameter ≥10mm, meet the requirements of the standard Response Evaluation Criteria In Solid Tumors(RESCIST) version 1.1).
- Disease progression within 12 months before inclusion.
- Subjects must be 131I-refractory / resistant as defined by at least one of the following;
- Lesions that do not demonstrate iodine uptake on any radioiodine scan;
- Subjects received a single radioactive iodine therapy within 12 months (≥ 3.7 Giga Bequerel(GBq)[≥ 100 millicurie(mCi)]) and target lesion disease progression;
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- Every two radioactive iodine treatment interval <12 months, doses ≥ 3.7 GBq [≥100mCi], disease progress more than 12 months after at least once iodine therapy;
- Received a total dose of radioactive iodine therapy ≥ 22.2 GBq (≥ 600 mCi);
- Normal main organ function:
- HB ≥ 90g / L;
- ANC ≥1.5×109/L;
- PLT ≥80×109/L;
- BIL <1.5 × ULN;
- ALT and AST <2.5 × ULN;
- Cr≤1×ULN;
- Eastern Cooperative Oncology Group(ECOG)Performance Status(PS) :0-2.
- An expected survival of ≥ 3 months.
- Pregnancy test (serum) has to be performed for woman of childbearing age within 7 days before enrolment and the test result must be negative. They shall take appropriate methods for contraception during the study until the 8th week post the last administration of study drug. For men, (previous surgical sterilization accepted), shall agree to take appropriate methods of contraception during the study until the 8th week post the last administration of study drug.
- Patient has to voluntarily join the study and sign the Informed Consent Form for the study.
- Good compliance is expected, according to the program requirements follow-up and recorded adverse reactions.
Who cannot join
- Other thyroid cancer histological subtypes (such as medullary carcinoma, lymphoma or sarcoma).
- Received VEGFR inhibitor (such as vandetanib, cabozantinib, lenvatinib, sunitinib, sorafenib, etc.) treatment within 1 months.
- Subjects with poor-controlled arterial hypertension (systolic blood pressure> 140 mmHg and diastolic blood pressure > 90 mm Hg) despite standard medical management; coronary heart disease greater than Class II; II-level arrhythmia (including QT interval prolongation, for man ≥ 450 ms, for woman ≥ 470 ms) together with Class II cardiac dysfunction.
- Factors that could have an effect on oral medication (such as inability to swallow, nausea, vomiting, chronic diarrhea and intestinal obstruction).
- Subjects with high gastrointestinal bleeding risk, including the following conditions: local active ulcer lesions with positive fecal occult blood test (++); history of black stool, or vomiting blood in the past 3 months.
- Abnormal Coagulation (INR>1.5、APTT>1.5 UNL), with tendency of bleed.
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- Disposition evidence of thrombosis/bleeding in 2 month (despite severity), hemoptysis in 2 months (bright red blood, 1/2 teaspoon).
- Arterial /venous thromboembolic events, such as cerebrovascular accident, deep vein thrombosis and pulmonary embolism in the past 12 months.
- Factors that could received radiotherapy or major surgery for anti - thyroid cancer in the past 28 days.
- Factors that could received surgery (allows the full-recovery wound) or active hemorrhage, ulceration, intestinal perforation or intestinal obstruction in the past 28 days.
- Uncontrolled infection.
- Pregnant or lactating women.
- Disposition evidence of depressive disorder (HAMD score ≥17).
- Other conditions regimented at investigators' discretion.
Trial locations and contacts
2 sites in 1 country.
China2 sites
Peking Union Medical College Hospital
Beijing, 100730
Nanjing PLA 81 Hospital
Nanjing, Jiangsu
About this study
Official title: A Randomized, Double-Blind, Placebo-Controlled Study of Apatinib in Locally Advanced or Metastatic Radioactive Iodine-refractory Differentiated Thyroid Cancer
Radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC) is a great challenge in the treatment of thyroid cancer. Tyrosine kinase inhibitors (TKIs), like sorafenib and lenvatinib which have been approved by food and drug administration (FDA), could not be affordable for most of the Chinese patients. Apatinib is a highly selective VEGFR2 inhibitor and reduces the angiogenesis of tumor effectively, which is a proven and effective drug in many solid tumors. A phase II study aims to assess the efficacy and safety of apatinib in RAIR-DTC ,which enrolled 20 patients and 10 of them had obtained a shout-term efficacy, demonstrating the peculiar potential in treatment of RAIR-DTC. In this study, the investigators aim to further explore the efficacy and safety of apatinib in RAIR-DTC.
Read the detailed description
Primary Outcome Measure: Progression free survival of apatinib in RAIR-DTC.
Secondary Outcome Measures: Disease control rate, objective response rate, duration of response, changes of Tg and TgAb level in serum, overall survival, side effects and quality of life.
- Conditions
- Differentiated Thyroid Cancer
- Being tested
- Apatinib Oral Tablet, Placebo Oral Tablet
- Keywords
- Radioactive iodine-refractory, differentiated thyroid cancer, Apatinib, anti-angiogenesis drugs
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Apatinib Oral TabletDrug
Apatinib Mesylate Tablets
Placebo Oral TabletDrug
Placebo Oral Tablet
| Study group | Role | What they receive |
|---|---|---|
| Apatinib | Experimental | Apatinib Mesylate Tablets Receives: Drug: Apatinib Oral Tablet |
| Placebo | Placebo comparator | Placebo Tablets Receives: Drug: Placebo Oral Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
PFS
Progression free survival
Measured: 24 months
Secondary outcomes (6)
DCR
Disease control rate
Measured: 24 months
ORR
Objective response rate
Measured: 24 months
DoR
Duration of response
Measured: 24 months
Changing trend of Tg and TgAb level in serum
Monitor the changes of Tg and TgAb level in serum regularly ( every 2~8 weeks, and addition examinations were needed if the participants' condition changed ) and draw the relevant changing curve to monitor the change of disease.
Measured: 24 months
OS
Overall survival
Measured: 24 months
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Record the number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Feb 2017 (estimated)
- Study startDec 2016
- Primary completion25 Mar 2020
- Study completion31 Dec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Differentiated Thyroid CancerStudies of the same condition, open and under way.
- More trials run by Peking Union Medical College HospitalThe 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized, Double-Blind, Placebo-Controlled
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 118 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Peking Union Medical College Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Yansong Lin, Peking Union Medical College Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03048877
- Sponsor's protocol ID
- PUMCH-NPLA81H-Ahead-T302
- Status last verified
- Apr 2023
- First submitted
- 3 Feb 2017
- Last updated
- 12 Apr 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Sun D, Zhang X, Jin X, Shi C, Sun Y, Zhang Y, Liang J, Lin Y. BRAFV600E mutation is associated with better prognoses in radioactive iodine refractory thyroid cancer patients treated with multi-kinase inhibitors: a retrospective analysis of registered clinical trials. Thyroid Res. 2025 Feb 10;18(1):5. doi: 10.1186/s13044-025-00223-0.
PubMed 39924483Zhu Y, Liu K, Wang K, Peng L. Vascular Endothelial Growth Factor Receptor Inhibitors in Chinese Patients With Advanced Radioactive Iodine-Refractory Differentiated Thyroid Cancer: A Network Meta-Analysis and Cost-Effectiveness Analysis. Front Endocrinol (Lausanne). 2022 Jul 14;13:909333. doi: 10.3389/fendo.2022.909333. eCollection 2022.
PubMed 35909569Lin Y, Qin S, Li Z, Yang H, Fu W, Li S, Chen W, Gao Z, Miao W, Xu H, Zhang Q, Zhao X, Bao J, Li L, Ren Y, Lin C, Jing S, Ma Q, Liang J, Chen G, Zhang H, Zhang Y, Zhou X, Sang Y, Hou Z. Apatinib vs Placebo in Patients With Locally Advanced or Metastatic, Radioactive Iodine-Refractory Differentiated Thyroid Cancer: The REALITY Randomized Clinical Trial. JAMA Oncol. 2022 Feb 1;8(2):242-250. doi: 10.1001/jamaoncol.2021.6268.
PubMed 34913959
Study at a glance
From the registry record, last updated by the sponsor on 12 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind, Placebo-Controlled Study of Apatinib in Locally Advanced or Metastatic Radioactive Iodine-refractory Differentiated Thyroid Cancer
- ClinicalTrials.gov ID
- NCT03048877
- Acronym / sponsor ID
- PUMCH-NPLA81H-Ahead-T302
- Conditions
- Differentiated Thyroid Cancer
- Keywords
- Radioactive iodine-refractory, differentiated thyroid cancer, Apatinib, anti-angiogenesis drugs
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 118 participants (estimated)
- Lead sponsor
- Peking Union Medical College HospitalUniversity, hospital or other
- Study start
- Dec 2016 (actual)
- Primary completion
- 25 Mar 2020 (actual)
- Study completion
- 31 Dec 2023 (estimated)
- First posted
- 9 Feb 2017 (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.
Radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC) is a great challenge in the treatment of thyroid cancer. Tyrosine kinase inhibitors (TKIs), like sorafenib and lenvatinib which have been approved by food and drug administration (FDA), could not be affordable for most of the Chinese patients. Apatinib is a highly selective VEGFR2 inhibitor and reduces the angiogenesis of tumor effectively, which is a proven and effective drug in many solid tumors. A phase II study aims to assess the efficacy and safety of apatinib in RAIR-DTC ,which enrolled 20 patients and 10 of them had obtained a shout-term efficacy, demonstrating the peculiar potential in treatment of RAIR-DTC. In this study, the investigators aim to further explore the efficacy and safety of apatinib in RAIR-DTC.
Detailed description
Primary Outcome Measure: Progression free survival of apatinib in RAIR-DTC.
Secondary Outcome Measures: Disease control rate, objective response rate, duration of response, changes of Tg and TgAb level in serum, overall survival, side effects and quality of life.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomized, Double-Blind, Placebo-Controlled
| Arm | Type | Receives |
|---|---|---|
| Apatinib | Experimental | Drug: Apatinib Oral TabletApatinib Mesylate Tablets |
| Placebo | Placebo comparator | Drug: Placebo Oral TabletPlacebo Tablets |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Aged after 18 years (18 is included).
- Locally advanced or metastatic differentiated thyroid cancer (papillary, follicular, Hurthle cells, poorly differentiated carcinoma). At least one measurable lesion (helical CT scan long diameter ≥10mm, meet the requirements of the standard Response Evaluation Criteria In Solid Tumors(RESCIST) version 1.1).
- Disease progression within 12 months before inclusion.
- Subjects must be 131I-refractory / resistant as defined by at least one of the following;
- Normal main organ function:
Key exclusion criteria (14 listed)
- Other thyroid cancer histological subtypes (such as medullary carcinoma, lymphoma or sarcoma).
- Received VEGFR inhibitor (such as vandetanib, cabozantinib, lenvatinib, sunitinib, sorafenib, etc.) treatment within 1 months.
- Subjects with poor-controlled arterial hypertension (systolic blood pressure> 140 mmHg and diastolic blood pressure > 90 mm Hg) despite standard medical management; coronary heart disease greater than Class II; II-level arrhythmia (including QT interval prolongation, for man ≥ 450 ms, for woman ≥ 470 ms) together with Class II cardiac dysfunction.
- Factors that could have an effect on oral medication (such as inability to swallow, nausea, vomiting, chronic diarrhea and intestinal obstruction).
- Subjects with high gastrointestinal bleeding risk, including the following conditions: local active ulcer lesions with positive fecal occult blood test (++); history of black stool, or vomiting blood in the past 3 months.
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 |
|---|---|---|
| Apatinib Oral TabletApatinib Mesylate Tablets | Drug | Apatinib |
| Placebo Oral TabletPlacebo Oral Tablet | Drug | Placebo |
Primary outcome
PFS
Time frame: 24 months
Progression free survival
6 secondary outcomes
DCR
Time frame: 24 months
ORR
Time frame: 24 months
DoR
Time frame: 24 months
Changing trend of Tg and TgAb level in serum
Time frame: 24 months
OS
Time frame: 24 months
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time frame: 24 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Apr 2023.
- Derived from this study: PubMed 39924483Sun D, Zhang X, Jin X, Shi C, Sun Y, Zhang Y, Liang J, Lin Y. BRAFV600E mutation is associated with better prognoses in radioactive iodine refractory thyroid cancer patients treated with multi-kinase inhibitors: a retrospective analysis of registered clinical trials. Thyroid Res. 2025 Feb 10;18(1):5. doi: 10.1186/s13044-025-00223-0.
- Derived from this study: PubMed 35909569Zhu Y, Liu K, Wang K, Peng L. Vascular Endothelial Growth Factor Receptor Inhibitors in Chinese Patients With Advanced Radioactive Iodine-Refractory Differentiated Thyroid Cancer: A Network Meta-Analysis and Cost-Effectiveness Analysis. Front Endocrinol (Lausanne). 2022 Jul 14;13:909333. doi: 10.3389/fendo.2022.909333. eCollection 2022.
- Derived from this study: PubMed 34913959Lin Y, Qin S, Li Z, Yang H, Fu W, Li S, Chen W, Gao Z, Miao W, Xu H, Zhang Q, Zhao X, Bao J, Li L, Ren Y, Lin C, Jing S, Ma Q, Liang J, Chen G, Zhang H, Zhang Y, Zhou X, Sang Y, Hou Z. Apatinib vs Placebo in Patients With Locally Advanced or Metastatic, Radioactive Iodine-Refractory Differentiated Thyroid Cancer: The REALITY Randomized Clinical Trial. JAMA Oncol. 2022 Feb 1;8(2):242-250. doi: 10.1001/jamaoncol.2021.6268.
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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.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Apatinib Oral Tablet in people with Differentiated Thyroid Cancer, run by Peking Union Medical College Hospital at 2 sites in China.
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 20 inclusion and 14 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: status not confirmed, as of the sponsor's last update on 12 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in China. 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. Some participants in this study may receive a placebo. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
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?
PFS (time frame: 24 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 NCT03048877, which also lists 3 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 12 Apr 2023.