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)

CSPC ZhongQi Pharmaceutical Technology Co., Ltd.13 sites in 1 country30 target enrollmentJuly 13, 2021

ConditionsMedullary Thyroid Carcinoma

InterventionsHA121-28 tablets

DrugsHA121-28 tablets

Overview

Phase: Phase 2
Intervention: HA121-28 tablets
Conditions: Medullary Thyroid Carcinoma
Sponsor: CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
Enrollment: 30
Locations: 13
Primary Endpoint: Objective remission rate (ORR)
Status: Recruiting
Last Updated: 4 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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).

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.

Registry

clinicaltrials.gov

Start Date

July 13, 2021

End Date

March 2025

Last Updated

4 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

CSPC ZhongQi Pharmaceutical Technology Co., Ltd.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Be willing to participate in the clinical trial and sign the informed consent;
•Men and women aged ≥18 years;
•Histologically confirmed unresectable locally advanced or metastatic MTC with at least one measurable lesion per RECIST1.1;
•Evidence of disease progression within 12 months prior to signing informed consent;
•Eastern Cooperative Oncology Group (ECOG) Performance Status of 0\~1;
•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；
•Left ventricular ejection fraction (LVEF)≥50% in echocardiogram；
•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;
•Female participants must have negative results of serum/urine pregnancy test within 7 days prior to enrollment and must not be breastfeeding.

Exclusion Criteria

•Previous treatment with selective RET inhibitor, such as blu-667, loxo-292, etc.;
•Patients who had participated in other clinical trials and received the treatment within 4 weeks prior to enrollment;
•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;;
•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;
•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;
•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;
•Urine protein≥2+ and urine protein \> 1.0 g/24h;
•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;
•Patients with spinal cord, meningeal and brain metastases (except for stable symptomatic or asymptomatic brain metastases);
•Ongoing adverse events\>grade 1 due to any previous treatment at the time of enrollment (except for hair loss and pigmentation);

Arms & Interventions

HA121-28 tablets

Patients will receive HA121-28 tablets at 450 mg once daily (QD) for 21 days on a 28-day treatment cycle.

Intervention: HA121-28 tablets

Outcomes

Primary Outcomes

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 Outcomes

Progression-free survival (PFS)(From date of randomization until the date of first documented progression, assessed up to 60 months)
Plasma drug concentration(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)
Changes in blood calcitonin(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)
Overall survival (OS)(From date of randomization until date of death from any cause, assessed up to 60 months)
Disease control rate (DCR)(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)
Duration of response (DOR)(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)
Adverse events incidence(From date of randomization until the date of death from any cause, assessed up to 60 months)