Clinical trial NCT04309968: Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK) and Anti-tumor Activity of SYHA1801 Monotherapy in Patients With Advanced Solid Tumors
Official title: A Phase I Clinical Trial Evaluating the Safety, Tolerability, Pharmacokinetic Characteristics and Preliminary Anti-tumor Activity of SYHA1801 Capsules in Patients With Advanced Solid Tumors.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Advanced Solid Tumors
Lead sponsor: CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2020-03-17
Enrollment: 186
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel Assignment
Primary purpose: TREATMENT

Brief summary: This is a safety, pharmacokinetic and pharmacodynamic study designed to estimate the maximum tolerated dose (MTD), and determine the Recommended Phase 2 Dose (RP2D) of SYHA1801, a BRD4 inhibitor in patients with advanced solid tumors.

Detailed description: This study will be performed in two parts. Part 1 will enroll patients with advanced solid tumors. Patients will receive SYHA1801 orally on Days 1 and 4-31 in the first cycle. Enrollment will follow a dose-escalation schedule until grade 3 drug-related adverse events are observed, at this point the i3+3 enrollment design will be used. Dose increments will be guided by data generated from previous levels. The dose and possibly the schedule will be adjusted to determine the Maximum Tolerated Dose (MTD). If a patient wishes to continuously receive study treatment on completion of Cycle 1, the patient can continue study treatment in 28-day Cycle 2 and subsequent cycles.

Part 2 will enroll patients with specific solid tumor which might potentially respond to BRD4 inhibitor. Patients will receive SYHA1801 at a dose and schedule established in Part 1.

Eligibility criteria: Inclusion Criteria:

1. Age ≥18, ≤75 years, no gender limitation.
2. Histologically or cytologically confirmed diagnosis of advanced or metastatic solid tumors, for which standard therapy either does not exist or has proven ineffective, intolerable or inacceptable for the patient.
3. At least one measurable lesion as per RECIST version 1.1.
4. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤1.
5. Life expectancy ≥3 months.
6. Adequate bone marrow reserve, renal and liver function.
7. Women of childbearing potential should agree to use contraceptive measures (such as IUD, contraceptive or condom) during the study and within 6 months after the end of the study; the serum pregnancy test should be negative within 7 days before enrollment, and must be non-lactating subjects; men should agree to use contraceptive measures during the study and within 6 months after the end of the study.
8. Signed informed consent form.

Exclusion Criteria:

1. Administration of chemotherapy, radiotherapy, biotherapy, endocrine therapy, targeted therapy, immunotherapy and other anti-tumor treatment within 4 weeks before the first dose of the study drug, except the following: using nitrosourea and mitomycin C within 6 weeks, using fluorouracil and small molecule targeted drugs within 2 weeks (or within 5 half time period), using traditional Chinese medicine with anti-tumor indications within 2 weeks.
2. Administration of other unlisted clinical research drugs within 4 weeks before the first dose of SYHA1801.
3. Major organ surgery (excluding biopsy) or significant trauma within 4 weeks before the first dose of SYHA1801.
4. Administration of glucocorticoids or other immunosuppressants within 14 days prior to the first dose of SYHA1801, except the following: local, ocular, intraarticular, intranasal and inhaled glucocorticoids; short-term use of glucocorticoids for preventive treatment.
5. Concomitant therapy with strong CYP3A4 inhibitors or inducers within 14 days.
6. Prior treatment with BET inhibitors.
7. Persistent grade \>1 clinically significant toxicity related to prior antineoplastic therapies (except alopecia).
8. Central nervous system metastasis or meningeal metastasis with clinical symptoms, or other evidence that the patient's central nervous system metastasis or meningeal metastasis has not been controlled, that is not suitable for the group according to the judgment of the investigator.
9. Uncontrollable active infection.
10. History of autoimmune diseases, immunodeficiency, including HIV positive, or other acquired, congenital immunodeficiency, or organ transplant history.
11. Active hepatitis B; positive for hepatitis C antibody.
12. History of serious cardiovascular disease.
13. Inability to swallow oral medications or presence of a gastrointestinal disorder deemed to jeopardize intestinal absorption of SYHA1801.
14. Other serious illness or medical conditions.
15. Alcohol or drug dependence.
16. A clear history of neurological or psychiatric disorders.
17. Pregnant or breast-feeding female.
18. In the opinion of the investigator, not suitable for enrollment due to other reasons.

Primary outcomes:
measure: To evaluate AE,SAE and DLT of SYHA1801.
timeFrame: 28 days
measure: To evaluate the MTD of SYHA1801
timeFrame: through study completion, an average of 1 year
Secondary outcomes:
measure: AUC0-last of SYHA1801.
timeFrame: 31 days
measure: AUC0-∞ of SYHA1801.
timeFrame: 31 days
measure: Cmax of SYHA1801.
timeFrame: 31 days
measure: Tmax of SYHA1801.
timeFrame: 31 days
measure: t½ of SYHA1801.
timeFrame: 31 days
measure: CL/F of SYHA1801.
timeFrame: 31 days
measure: ORR of SYHA1801
timeFrame: 2 months
measure: PFS of SYHA1801
timeFrame: 2 months
measure: DCR of SYHA1801
timeFrame: 2 months
measure: DOR of SYHA1801
timeFrame: 2 months
Other outcomes:
measure: Biomarkers and Beneficiaries
timeFrame: 2 months
Locations:
city: Tianjin
country: China
facility: Tianjin Cancer Hospital
state: Tianjin
Study officials:
References: