Study of Anlotinib in Patients With Radioiodine Refractory Differentiated Thyroid Cancer

An Exploratory Study to Evaluate the Efficacy of Anlotinib Hydrochloride Combined With Penpulimab in the Treatment of Radioiodine Refractory Differentiated Thyroid Cancer With First-line Resistance to Angiogenesis Inhibitors

This study aims to observe and explore the efficacy and safety of Anlotinib combined with penpulimab in the treatment of radioiodine refractory differentiated thyroid cancer with first-line resistance to angiogenesis inhibitors, and to summarize the treatment experience of population.

Study Overview

• Status: Not yet recruiting
• Conditions: Locally Advanced or Metastatic Radioiodine-refractory Differentiated Thyroid Carcinoma
• Intervention / Treatment: Drug: Anlotinib Hydrochloride Capsule and Penpulimab

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100007
      • YansongLin
      • Contact: Yansong Lin, PhD; Phone Number: 13671116837; Email: linys@pumch.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients voluntarily joined the study, signed the informed consent;
2. Patients were pathologically confirmed as locally advanced or metastatic differentiated thyroid cancer (DTC), having at least one measurable lesion (Response Evaluation Criteria In Solid Tumors (RECIST) 1.1);
3. Patients≥18 years of age; Eastern Cooperative Oncology Group Performance Status (ECOG-PS) score: 0-2; Expected survival of more than 6 months;
4. Possessing imaging or clinical evidence of disease progression within the first 18 months of enrollment;
5. Progression of at least one anti-vascular drug（no more than 2）；
6. Tg and structural imaging examinations were performed at least twice before enrollment；
7. Meet any of the following while meeting the above 3 items:（1）Lesions were not iodine-avid；（2） The cumulative dose of RAI was ≥ 600 mCi or 22 GBq, with an interval of at least 3 months. （3） Radiographically documented disease progression within 18 months of RAI therapy despite the presence of iodine-131 affinity at the time of RAI therapy;

8. Major organ functions meet the following criteria within 7 days prior to the treatment:

   1. Hemoglobin (Hb) ≥90g/L;
   2. Absolute Neutrophil Count (ANC) ≥1.5×109/L;
   3. Platelet (PLT) ≥80×109/L；
   4. Total bilirubin (TBIL) ≤1.5 times the upper limit of normal (ULN);
   5. Alanine transferase (ALT) and Aspartate transferase (AST) ≤2.5×ULN; If accompanied by liver metastasis, ALT and AST ≤5×ULN； (f)Serum creatinine (Cr) ≤1.5×ULN or Creatinine clearance rate (CCr) ≥60ml/min； (g) The left ventricular ejection fraction was at least 50% of the normal level.
9. Female patients of reproductive age should agree that birth control (such as intrauterine device, birth control pills, or condoms) must be used during the study period and for six months after completion; Having a negative serum pregnancy test within 7 days prior to study enrollment, and must be non-lactating; Male patients should agree to use contraception during the study period and for six months after the end of the study.

Exclusion Criteria:

1. Complicated diseases and history:

   1. Histologic subtypes of thyroid cancer other than the differentiated type (e.g., medullary carcinoma, lymphoma, or sarcoma) could not be enrolled; Patients currently have or had other malignancies within 5years. Cured localized tumors could be enrolled（e.g., Skin basal cell carcinoma）

   2. Subjects with any severe and/or uncontrolled heart disease, including:

      1. According to the criteria of New York Heart Association (NYHA) grade II or above cardiac insufficiency or echocardiography: LVEF (left ventricular ejection fraction) <50%;
      2. Unstable angina
      3. A myocardial infarction had occurred within 1 year before the beginning of the treatment
      4. Clinically significant supraventricular or ventricular arrhythmias require treatment or intervention
      5. QTc ≥450ms (male), QTc ≥470ms (female) (classified by New York heart association, NYHA);
2. Other anti-tumor treatment (including but not limited to chemotherapy, radiotherapy, etc.). were received within 28 days before the beginning of the treatment; TSH suppression therapy was excluded;
3. Patients who have previously used immune checkpoint inhibitors (including but not limited to nivolumab, pembrolizumab, toripalimab, sintilimab, etc.);

5) Patients with hypertension that was not falling to the normal range with antihypertensive medication (systolic blood pressure ≥140mmHg or diastolic blood pressure ≥90mmHg) were allowed to use antihypertensive treatment to achieve these parameters. Hypertensive crisis or hypertensive encephalopathy.

6) Multiple factors affect the absorption of oral drugs. 7）Patients at risk for gastrointestinal bleeding were not eligible, including the following: (1) patients with active peptic ulcer lesions and fecal occult blood (++); (2) patients with a history of melena and hematemesis within 3 months; 8). Active or uncontrolled severe infection (≥ Common Terminology Criteria for Adverse Events (CTC AE) 2 grade of infection); 9) Patients with concomitant diseases that, in the investigator's judgment, may seriously endanger patients' safety or may interfere with the completion of the study, or are deemed unsuitable for inclusion for other reasons.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Anlotinib+ penpulimab; Anlotinib：12 mg once daily for 2 weeks, followed by a rest of 1 week (21-day cycle)； Penpulimab：200mg Q3 W

Drug: Anlotinib Hydrochloride Capsule and Penpulimab; Anlotinib hydrochloride is a muti-target tyrosine kinase inhibitor that inhibits both tumor angiogenesis and tumor cell proliferation by blocking VEGFR, FGFR, PDGFR, and c-Kit simultaneously. Penpulimab is a novel structure Immune checkpoint inhibitor. The combination of Penpulimab and RAI might have synergistic effects for DTC.; Other Names: Penpulimab; Anlotinib Hydrochloride Capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)	The proportion of subjects who achieves a best overall response of CR(Complete Response) or PR(Partial response).	Baseline up to 2 years.
changes in Tg level	The percentage of decrease in serum Tg from baseline;	Baseline up to 2 years.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Response（DOR）	From the date that CR or PR are first occurred to the date of objective disease progression or death, whichever occurs first.	Baseline up to 2 years.
Progression-free Survival (PFS)	From the first dose of Anlotinib to the date of objective disease progression or death, whichever occurs first	Baseline up to 2 years.
Disease-control Rate（DCR）	The proportion of subjects response of CR, PR, or SD(Stable disease) (subjects achieving SD will be included in the DCR if they maintain SD for ≥4 weeks).	Baseline up to 2 years.
Overall Survival（OS）	From randomization to the time of death from any cause.	Baseline up to 2 years.
Time to response(TTR)	From randomization to the time of response from any cause.	Baseline up to 2 years.

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): November 11, 2023
• Primary Completion (Estimated): December 20, 2024
• Study Completion (Estimated): August 20, 2025

Study Registration Dates

• First Submitted: September 25, 2023
• First Submitted That Met QC Criteria: September 25, 2023
• First Posted (Actual): October 2, 2023

Study Record Updates

• Last Update Posted (Actual): October 2, 2023
• Last Update Submitted That Met QC Criteria: September 25, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Endocrine System Diseases; Endocrine Gland Neoplasms; Head and Neck Neoplasms; Thyroid Diseases; Thyroid Neoplasms
• Other Study ID Numbers: T004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No