A Study of HA121-28 Tablets in Patients With Medullary Thyroid Carcinoma (MTC)

• ClinicalTrials.gov Identifier: NCT04787328
• Recruitment Status: Recruiting
• First Posted: March 8, 2021
• Last Update Posted: February 23, 2022
• Sponsor: CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
• Information provided by (Responsible Party): CSPC ZhongQi Pharmaceutical Technology Co., Ltd.

Study Description

Brief Summary:

This is a single-arm, open-label, multicenter study designed to evaluate the preliminary antineoplastic activity, safety and tolerability of HA121-28 tablets administered orally in patients with medullary thyroid cancer (MTC).

Condition or disease	Intervention/treatment	Phase
Medullary Thyroid Carcinoma	Drug: HA121-28 tablets	Phase 2

Detailed Description:

A total of approximately 30 patients with MTC will be enrolled. The patients will undergo a 3 weeks-on and 1week-off treatment scheme with HA121-28 tablets 450 mg orally once daily in the 28-day cycle until disease progression or intolerable toxic reaction, whichever occurs first. During the administration of HA121-28 tablets, vital signs, physical examination, ECOG performance status, hematology and chemistry test, ECG, adverse events and concomitant drugs will be evaluated every four weeks, an additional ECG will be observed two weeks after the first dose, calcitonin and pregnancy test will be performed every 8 weeks. CT for tumor assessment will be performed every 8 weeks for the first year, and every 12 weeks thereafter.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 30 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Single-arm, Open-Label, Multicenter Phase II Study to Evaluate the Efficacy and Safety of HA121-28 Tablets in Patients With Medullary Thyroid Carcinoma (MTC)
• Actual Study Start Date: July 13, 2021
• Estimated Primary Completion Date: March 2023
• Estimated Study Completion Date: March 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: HA121-28 tablets; Patients will receive HA121-28 tablets at 450 mg once daily (QD) for 21 days on a 28-day treatment cycle.	Drug: HA121-28 tablets; HA121-28 450 mg, po, QD×21 days, every 4 weeks (28 days)

Outcome Measures

Primary Outcome Measures :

1. Objective remission rate (ORR) [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause,whichever came first, assessed up to 60 months ]
   assessed approximately every 8 weeks or 12 weeks based on the treatment cycle

Secondary Outcome Measures :

1. Progression-free survival (PFS) [ Time Frame: From date of randomization until the date of first documented progression, assessed up to 60 months ]
   assessed approximately every 8 weeks or 12 weeks based on the treatment cycle
2. Duration of response (DOR) [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause,whichever came first, assessed up to 60 months ]
   assessed approximately every 8 weeks or 12 weeks based on the treatment cycle
3. Overall survival (OS) [ Time Frame: From date of randomization until date of death from any cause, assessed up to 60 months ]
   assessed approximately every 12 weeks
4. Disease control rate (DCR) [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause,whichever came first, assessed up to 60 months ]
   assessed approximately every 8 weeks or 12 weeks based on the treatment cycle
5. Changes in blood calcitonin [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, or date of death from any cause,whichever came first, assessed up to 60 months ]
   assessed approximately every 8 weeks
6. Adverse events incidence [ Time Frame: From date of randomization until the date of death from any cause, assessed up to 60 months ]
   assessed approximately every 4 weeks
7. Plasma drug concentration [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, wihichever came first, assessed up to 60 months ]
   assessed approximately every 4 weeks

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Be willing to participate in the clinical trial and sign the informed consent;
2. Men and women aged ≥18 years;
3. Histologically confirmed unresectable locally advanced or metastatic MTC with at least one measurable lesion per RECIST1.1;
4. Evidence of disease progression within 12 months prior to signing informed consent;
5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0~1;
6. Laboratory test results must meet the following criteria: Absolute neutrophil count (ANC) ≥1.5 x 10^9/L; Platelet count (PLT) ≥75×10^9/L; Hemoglobin (Hb) ≥90 g/L; Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 x upper limit of normal (ULN) (in patients with liver metastasis ≤5.0 x ULN); Total bilirubin ≤ 1.5 x ULN; Serum creatinine≤ 1.5 x ULN；Prothrombin time (PT) and activated Partial Thromboplastin Time (APTT) ≤ 1.5 x ULN；
7. Left ventricular ejection fraction (LVEF)≥50% in echocardiogram；
8. Male and female subjects of childbearing potential must agree to take effective contraception during the treatment period and for 6 months after the last dose of study medication;
9. Female participants must have negative results of serum/urine pregnancy test within 7 days prior to enrollment and must not be breastfeeding.

Exclusion Criteria:

1. Previous treatment with selective RET inhibitor, such as blu-667, loxo-292, etc.;
2. Patients who had participated in other clinical trials and received the treatment within 4 weeks prior to enrollment;
3. Systemic anti-tumor treatment such as small molecule targeted drugs, cytotoxic drugs, immunotherapy and radiotherapy within 4 weeks of the first dose of the study drug, or local palliative radiotherapy for pain relief within 2 weeks;;
4. Patients who cannot swallow or have chronic diarrhea (except for those induced by MTC) and intestinal obstruction, or other factors which may affect the administration and absorption of the study drug;
5. History of other malignancies within the past 5 years or currently suffering from other malignancies, except for cured cervical carcinoma in situ, non-melanoma skin cancer, and superficial bladder tumor;
6. Patients who meet one of the following criteria: 1) Corrected QT (QTc) ≥450 ms (corrected using Fridericia's formula (QTcF): QTcF = QT/(RR^0.33)); 2) Any clinically significant abnormalities of rhythm, conduction or morphology in the resting electrocardiogram (ECG) requiring therapeutic intervention;
7. Urine protein≥2+ and urine protein > 1.0 g/24h;
8. Known severe concomitant and/or uncontrolled diseases, including but not limited to: 1)Uncontrolled hypertension (systolic pressure ≥150 mmHg or diastolic pressure ≥100 mmHg, after treatment); 2)Significant cardiovascular and cerebrovascular events, arterial or venous fistulae thrombotic events, myocardial infarction, congestive heart failure (NYHA classification ≥2) or severe ventricular arrhythmia within 6 months of the first dose of the study drug; 3) Liver cirrhosis, decompensated liver disease; 4) Renal failure required hemodialysis or peritoneal dialysis; 5) History of human immunodeficiency, including HIV positive, or other acquired/congenital immune deficiency diseases, or history of organ or bone marrow transplantation; 6) Uncontrolled pericardial effusion, pleural effusion or ascites;7） interstitial pneumonia required steroid therapy or severe infection required systemic treatment, which is judged not suitable for the study by the investigator;
9. Patients with spinal cord, meningeal and brain metastases (except for stable symptomatic or asymptomatic brain metastases);
10. Ongoing adverse events>grade 1 due to any previous treatment at the time of enrollment (except for hair loss and pigmentation);
11. Patients who have undergone major surgery or have not recovered from invasive operation within 4 weeks prior to initiation of study treatment;
12. Patients with bleeding diathesis (such as active peptic ulcer) or treated with anticoagulants or vitamin K antagonists, such as warfarin, heparin or their analogues;
13. Known active Hepatitis B or Hepatitis C virus infection: HBsAg positive with HBV DNA higher than the lower limit of detection range of the site, or HCV antibody positive with HCV RNA higher than the lower limit of detection range of the site);
14. Patients with known history of neurological or psychiatric disorders, including epilepsy or dementia;
15. Not suitable for the study assessed by the investigators.

Contacts and Locations

Contacts

Contact: Ming Gao, PhD; 022-27557550; gming68@aliyun.com

Locations

China, Beijing

Beijing Tongren Hospital; Not yet recruiting

Beijing, Beijing, China, 100000

Contact: Xiaohong Xiaohong 13911071002 trchxh@163.com

Cancer Institute and Hospital, Chinese Academy of Medical Sciences; Not yet recruiting

Beijing, Beijing, China, 100021

China, Fujian

Fujian Cancer Hospital; Recruiting

Fuzhou, Fujian, China, 350014

Contact: Hui Liu 138 0506 9511 liuhuifj@sina.com

China, Gansu

Gansu Province Tumor Hospital; Not yet recruiting

Lanzhou, Gansu, China, 730000

Contact: Qinjiang Liu 13519607327

China, Guangdong

Sun Yat-Sen University Cancer Center; Recruiting

Guangzhou, Guangdong, China, 510080

Contact: Ankui Yang 13903052829 yangak@sysucc.org.cn

China, Henan

Henan Province Tumor Hospital; Not yet recruiting

Zhengzhou, Henan, China, 450003

Contact: Jianwu Qin 13598802366 qinjianwu62@163.com

China, Jiangsu

Jiangsu province tumor hospital; Not yet recruiting

Nanjing, Jiangsu, China

Contact: Yuan Zhang 13915990202 ctc@jszlyy.com.cn

China, Shanghai

Cancer Hospital of Fudan University; Not yet recruiting

Shanghai, Shanghai, China, 200032

Contact: Yu Wang 13817311886 neck130@hotmail.com

China, Sichuan

Sichuan Cancer Hospital; Not yet recruiting

Chengdu, Sichuan, China, 610041

Contact: Chao Li 18081892592

China, Tianjin

Tianjin Medical University Cancer Institute and Hospital; Not yet recruiting

Tianjin, Tianjin, China, 300600

Contact: Xiangqian Zheng 13820881516 headandneck2007@aliyun.com

Tianjin People's Hospital; Recruiting

Tianjin, Tianjin, China, 300600

Contact: Ming Gao, PhD 022-27557550 gming68@aliyun.com

China, Yunnan

The First Affiliated Hospital of Kunming Medical University; Not yet recruiting

Kunming, Yunnan, China, 650032

Contact: Ruochuan Cheng 13708467986 cruochuan@foxmail.com

China, Zhejiang

Zhejiang Provincial People's Hospital; Not yet recruiting

Hangzhou, Zhejiang, China, 310022

Contact: Minghua Ge 13605813782 gemingh@163.COM

Sponsors and Collaborators

CSPC ZhongQi Pharmaceutical Technology Co., Ltd.

Investigators

• Study Director: Wen Xu, Master; CSPC ZhongQi Pharmaceutical Technology Co., Ltd.

More Information

• Responsible Party: CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
• ClinicalTrials.gov Identifier: NCT04787328
• Other Study ID Numbers: HA122-CSP-003
• First Posted: March 8, 2021
• Last Update Posted: February 23, 2022
• Last Verified: February 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Thyroid Neoplasms; Thyroid Diseases; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Carcinoma; Carcinoma, Neuroendocrine; Endocrine System Diseases; Adenocarcinoma