Study of Dosage Exploration and Pharmacokinetics for HA121-28 Tablets

NCT03994484 | Unknown Phase 1

• 1 other identifier: HA121-28/2017/01
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

There are 2 phases in this study: Phase 1 (dose escalation) and Phase 2 (dose expansion). The goal of Phase 1 of this clinical research study is to find the highest tolerable dose of HA121-28 tablets that can be given to patients with advanced cancer. The goal of Phase 2 of this study is to learn if the dose of HA121-28 tablets found in Phase 1 can help to control advanced cancer. The safety of HA121-28 tablets will be studied in both phases of the study.

Conditions

Advanced Solid Tumor

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) of HA121-28 tablets in Advanced and/or Metastatic Cancer Refractory to Standard Treatment

  MTD defined by dose limiting toxicities (DLTs) that occur in the first cycle. DLT defined as any clinically grade 3 or 4 non-hematologic toxicity as defined in the NCI CTC v4.0

  At the end of Cycle 1 (each cycle is 28 days)

Secondary Outcomes (1)

• Antitumor Efficacy of HA121-28 tablets: RECIST criteria version 1.1.

  up to 24 weeks

Study Arms (1)

HA121-28 tables

EXPERIMENTAL

Participants will receive oral HA121-28 at a starting dose of 25 mg once daily at the 1st day in 0 cycle and for 21 days on a 28-day treatment cycle

Drug: HA121-28 tablets

Interventions

HA121-28 tablets DRUG

Participants will receive oral HA121-28 at a starting dose of 25 mg once daily at the 1st day in 0 cycle and for 21 days on a 28-day treatment cycle

HA121-28 tables

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be willing to participate in the clinical trial and sign the informed consent;
• Men and women aged 18 to 75 years;
• Histologically/cytologically confirmed advanced/metastatic solid tumor, and have failed prior standard therapy or for which no standard therapy is durable(patients with RET fusion/mutation can be included regardless of whether they have received standard therapy or not);
• At least one measurable lesion according to RECIST 1.1 ;
• Subject has not received any anti-cancer therapies including chemotherapy, radiotherapy, targeted treatment and surgery within 4 weeks prior to participation;
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0\~1;
• Expected overall survival (Life expectancy)≥ 3 months;
• Laboratory test results must meet the following standards:
• Absolute neutrophil count (ANC) ≥1.5 x 10\^9/L; Platelet count (PLT) ≥75×10\^9/L; Hemoglobin (Hb) ≥90 g/L (no blood transfusion within 14 days); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 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；
• Male and female subjects of childbearing potential should agree to use suitable method of contraception during the treatment and 6 months after the last dose of study medication; female participants should have negative results of serum/urine pregnancy test within 7 days prior to enrollment and cannot be breastfeeding.

You may not qualify if:

• Has participated in other clinical trials and received the treatment within 4 weeks prior to enrollment;
• Patients who cannot swallow or have chronic diarrhea and intestinal obstruction, which may affect the administration and absorption of the drug;
• Subject who meets one of the following criteria:
• Corrected QT (QTc) ≥470ms in women, ≥450ms in men; or congenital long QT syndrome (LQTS), taking QT prolonging medications, and has a family history of long QT syndrome;
• Resting ECG result shows clinically significant abnormalities of rhythm, conduction or morphology, requiring therapeutic intervention;
• Urinalysis result shows protein in urine ≥ ++ and 24-hour urine protein \> 1.0g;
• Based on the investigator's assessment, patients with known severe comorbidities which may influence the safety of the patients and the study completion \[such as uncontrolled hypertension (systolic pressure ≥150 mmHg or diastolic pressure ≥100 mmHg, despite treated with the optimal medicine), diabetes, etc.\];
• Patients who have symptoms of metastatic brain/meningeal tumors within 4 weeks of participation;
• Ongoing adverse events\>grade 1 at the time of participation (except hair loss and pigmentation);
• Patients who have undergone major surgery or have not recovered from Invasive operation within 4 weeks prior to initiation of study treatment;
• Coagulation disorders (INR \>1.5, prothrombin time (PT) \> ULN+4s or APTT \>1.5ULN): with bleeding diathesis (such as active peptic ulcer) or receiving thrombolytic or anti-coagulant treatment;
• Known pulmonary infection/ pneumonitis / interstitial pneumonia who are not suitable for the research;
• Known active Hepatitis B or Hepatitis C virus infection;
• if HBsAg result is positive, additional HBV DNA testing is required (the result is higher than the ULN of the research center);
• if HCV antibody result is positive, additional HCV RNA testing is required (the result is higher than the ULN of the research center);

Sponsors & Collaborators

• CSPC ZhongQi Pharmaceutical Technology Co., Ltd.: lead

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510000, China

RECRUITING

Related Publications (1)

• Ruan DY, Huang WW, Li Y, Zhao Y, Shi Y, Jia Y, Cang S, Zhang W, Shi J, Chen J, Lin J, Liu Y, Xu J, Ouyang W, Fang J, Zhuang W, Liu C, Bu Q, Li M, Meng X, Sun M, Yang N, Dong X, Pan Y, Li X, Qu X, Zhang T, Yuan X, Hu S, Guo W, Li Y, Li S, Liu D, Song F, Tan L, Yu Y, Yu X, Zang A, Sun C, Zhang Q, Zou K, Dan M, Xu RH, Zhao H. Safety, pharmacokinetics and efficacy of HA121-28 in patients with advanced solid tumors and RET fusion-positive non-small-cell lung cancer: a multicenter, open-label, single-arm phase 1/2 trial. Signal Transduct Target Ther. 2025 Feb 28;10(1):62. doi: 10.1038/s41392-025-02155-5.

  PMID: 40016191 DERIVED

Study Officials

• Wen Xu

  Clinical Medicine Department CSPC R&D Business Division

  STUDY DIRECTOR

Central Study Contacts

Wen Xu

CONTACT

1850063169; xuwen@mail.ecspc.com

Chuan Yang

CONTACT

18224456799; yangchuan@mail.ecspc.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 18, 2019
• First Posted: June 21, 2019
• Study Start: October 10, 2018
• Primary Completion: December 30, 2022
• Study Completion: December 30, 2022
• Last Updated: February 10, 2022

Record last verified: 2022-02

Locations

CN (1)