Clinical trial NCT03994484: Study of Dosage Exploration and Pharmacokinetics for HA121-28 Tablets
Official title: Pharmacokinetics of Single and Multiple Doses of HA121-28 Tablets and Exploration of Maximum Tolerated Dose in Patients With Advanced Solid Tumor in PhaseⅠClinical Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Advanced Solid Tumor
Lead sponsor: CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2019-06-21
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Detailed description: If participants are found to be eligible to take part in this study, they will be assigned to a study group based on when they join this study. Up to 8 groups of up to 20 participants will be enrolled in Phase 1 of the study, and up to 3 groups of up to 24 participants will be enrolled in Phase 2.

If participant is enrolled in Phase 1, the dose of HA121-28 tablets they receive will depend on when they join this study. The first group of participants will receive the lowest dose level of HA121-28 tablets. Each new group will receive a higher dose of HA121-28 tablets than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of HA121-28 tablets is found. If participant is enrolled in Phase 2, they will receive HA121-28 tablets at the low, medium and high doses to select the recommended dose for phase Ⅱ clinical trials.

Eligibility criteria: Inclusion Criteria:

1. Be willing to participate in the clinical trial and sign the informed consent;
2. Men and women aged 18 to 75 years;
3. 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);
4. At least one measurable lesion according to RECIST 1.1 ;
5. Subject has not received any anti-cancer therapies including chemotherapy, radiotherapy, targeted treatment and surgery within 4 weeks prior to participation;
6. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0\~1;
7. Expected overall survival (Life expectancy)≥ 3 months;
8. 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；
9. 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.

Exclusion Criteria:

1. Has participated in other clinical trials and received the treatment within 4 weeks prior to enrollment;
2. Patients who cannot swallow or have chronic diarrhea and intestinal obstruction, which may affect the administration and absorption of the drug;
3. 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;
4. Urinalysis result shows protein in urine ≥ ++ and 24-hour urine protein \> 1.0g;
5. Based on the investigator's assessment, patients with known severe comorbidities which may influence the safety of the patients and the study completion \[such as uncontrolled hypertension (systolic pressure ≥150 mmHg or diastolic pressure ≥100 mmHg, despite treated with the optimal medicine), diabetes, etc.\];
6. Patients who have symptoms of metastatic brain/meningeal tumors within 4 weeks of participation;
7. Ongoing adverse events\>grade 1 at the time of participation (except hair loss and pigmentation);
8. Patients who have undergone major surgery or have not recovered from Invasive operation within 4 weeks prior to initiation of study treatment;
9. 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;
10. Known pulmonary infection/ pneumonitis / interstitial pneumonia who are not suitable for the research;
11. 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);
12. Known history of human immunodeficiency virus (HIV), or other acquired/congenital immune deficiency diseases or organ transplantation;
13. Other anti-tumor therapies are required (including radiotherapy, chemotherapy, immunotherapy, targeted treatment, traditional Chinese medicine, etc.);
14. Patients with known history of neurological or psychiatric disorders, including epilepsy or dementia;
15. Not suitable for the treatment assessed by the researchers;
16. Cardiac ejection fraction less than 50%;
17. Patients who have suffered from or are complicated with any other malignant tumor within 5 years (except radically resected skin basal cell carcinoma, skin squamous cell carcinoma, superficial bladder cancer, local prostate cancer, in situ cervical cancer or other carcinoma in situ).

Primary outcomes:
measure: Maximum Tolerated Dose (MTD) of HA121-28 tablets in Advanced and/or Metastatic Cancer Refractory to Standard Treatment
timeFrame: At the end of Cycle 1 (each cycle is 28 days)
Secondary outcomes:
measure: Antitumor Efficacy of HA121-28 tablets: RECIST criteria version 1.1.
timeFrame: up to 24 weeks
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
Study officials:
affiliation: Clinical Medicine Department CSPC R&D Business Division
name: Wen Xu
role: STUDY_DIRECTOR
References: