Clinical trial NCT04049929: A Phase I Study of YY-20394 in Patients With Advanced Solid Tumors
Official title: A Single-Arm, Open-Label, Multi-Center, Phase I Study of YY-20394 in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Advanced Solid Tumor
Keywords: YY-20394
Advanced solid tumor
Lead sponsor: Shanghai YingLi Pharmaceutical Co. Ltd.
Sponsor class: INDUSTRY
First posted: 2019-08-08
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Protocol YY-20394-003 is a phase I single arm, open label study. The primary objective is to assess the safety of YY-20394 in subjects with advanced solid tumor. The secondary objective is to determine the preliminary efficacy and pharmacokinetics (PK).

Detailed description: In this clinical trials, patients will be dosed YY-20394 orally at 80mg per day until disease progression, unacceptable toxicity, or withdrawal from the study. A treatment cycle is defined as 28 days. Drug safety will be evaluated by NCI-CTC AE5.0 every week within 28 days after first dose and every 2 weeks in the following cycles. Efficacy will be assessed by RECIST1.1 after 2 cycles.

Eligibility criteria: Inclusion Criteria:

1. Males and/or females over age 18
2. Histologically or cytologically confirmed advanced solid tumors. Failure or lack of standard treatment.
3. Eastern Cooperative Oncology Group performance status of 0 to 2
4. Life expectancy of at least 3 months
5. At least one measurable lesion according to RECIST1.1.
6. Acceptable hematologic status:

   Absolute neutrophil count(ANC)≥1.5×10\^9/L; Platelet count(PLT)≥75×10\^9/L; Hemoglobin(Hb)≥80 g/L; Total bilirubin(TBIL)≤1.5×Upper limit of normal value(ULN); Alanine aminotransferase(ALT)≤1.5×ULN; Aspartate aminotransferase(AST)≤1.5×ULN; Creatinine(Cr)≤1.5×ULN; Left Ventricular Ejection Fractions(LVEF)≥50%； QTcF：male\<450 ms,female\<470 ms
7. Accept to use proper contraceptives throughout the study period and within 6 months after the last dose.
8. Ability to respect the protocol approved by investigator.
9. Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

1. Previously treated with PI3Kδ inhibitors and cause disease progression (removed from the study because of intolerance is not included).
2. Any anti-tumor treatment, within 4 weeks prior to study entry, such as chemotherapy, radiotherapy and immunotherapy. Nitrosoureas or mitomycin C within 6 weeks prior to study entry. Oral drug of fluorouracil or small molecular targeted drugs 2 weeks prior to study entry.
3. Any other investigational agents within 4 weeks prior to study entry.
4. Any surgery on main organ (needle biopsy not included) or serious injury within 4 weeks prior to study entry. Selective operation is required during the study period.
5. Adverse events of previous anti-cancer treatment have not recovered to CTCAE v5.0 ≤1.
6. There are third interstitial effusions (such as massive pleural effusion and ascites) which can not be controlled by drainage or other methods.
7. The dosage of steroid hormone (prednisone equivalent) was greater than 20mg/day, and lasted for more than 14 days.
8. Medical history of difficulty in swallowing, malabsorption, or other chronic gastrointestinal disease, or conditions that may hamper compliance and/or absorption of the tested drug.
9. During the study period, drugs that may prolong the QT (such as anti arrhythmic drugs) could not be interrupted.
10. Patients with central nervous system (CNS) matastasis or meningeal metastasis with clinical symptoms, or there are evidences of CNS matastasis or meningeal metastasis uncontrolled approved by investigators.
11. Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy(such as pneumonia).
12. Active hepatitis b (HBV titers\>1000 copies/ml or 200IU/ml), prophylactic antiviral therapies other than interferon are allowed. Patients with Hepatitis C virus (hepatitis C antibody test positive).
13. History of immunodeficiency, including HIV positive test, other acquired or congenital immunodeficiency disorders, organ transplantation or allogeneic bone marrow transplantation.
14. Has suffered from any heart disease within 6 months prior to study entry, including: (1) angina pectoris; (2) medicated or clinically significant arrhythmia; (3) myocardial infarction; (4) heart failure; (5) any other heart disease judged by the researchers not suitable for the test.
15. The baseline pregnancy test was positive in pregnant women, lactating women or fertile women.
16. According to the judgement of the investigator, there are concomitant diseases that seriously endanger the safety of patients or affect the completion of the study (such as severe hypertension, diabetes, thyroid diseases, etc.
17. Patients suffering from other primary malignant tumors in the past 5 years. Patients with curable local tumors (such as basal or squamous cell carcinoma, superficial bladder cancer, carcinoma in situ of the cervix or of the breast) could be enrolled after completely cured.

Primary outcomes:
measure: Adverse events evaluated by NCI CTCAE v5.0
timeFrame: with in 2 years after the first dose
Secondary outcomes:
measure: Objective response rate
timeFrame: with in 56 days after the first dose
measure: Disease control rate
timeFrame: with in 56 days after the first dose
measure: Maximum concentration (Cmax)
timeFrame: 10 mins pre-dose in D1, D7, D14; 0.5, 1, 2, 4, 6, 8, 24 hours after the first dose
measure: Time to maximum concentration (Tmax)
timeFrame: 10 mins pre-dose in D1, D7, D14; 0.5, 1, 2, 4, 6, 8, 24 hours after the first dose
measure: Minimum concentration(Cmin)
timeFrame: 10 mins pre-dose in D1, D7, D14; 0.5, 1, 2, 4, 6, 8, 24 hours after the first dose
measure: Area under the curve (AUC)
timeFrame: 10 mins pre-dose in D1, D7, D14; 0.5, 1, 2, 4, 6, 8, 24 hours after the first dose
measure: Half-life (t1/2)
timeFrame: 10 mins pre-dose in D1, D7, D14; 0.5, 1, 2, 4, 6, 8, 24 hours after the first dose
measure: Clearance (CL)
timeFrame: 10 mins pre-dose in D1, D7, D14; 0.5, 1, 2, 4, 6, 8, 24 hours after the first dose
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai East Hospital
state: Shanghai
Study officials:
affiliation: Shanghai YingLi Pharmaceutical Co. Ltd.
name: Hanying Bao, PhD
role: STUDY_DIRECTOR
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