A Study of HQP1351 in Patients With GIST or Other Solid Tumors
Study Details
Study Description
Brief Summary
This study is a Multi-center, Open-label Phase 1 Study to Determine the Recommend Phase 2 Dose (RP2D) and Evaluate PK/PD and preliminary Efficacy of HQP1351 in Patients With GIST or Other Solid Tumors.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Detailed Description
The primary objective of this phase 1 study is to determine the RP2D of HQP1351 in patients with GIST or other solid tumors. The secondary objective is to assess the safety, tolerability, PK and preliminary anti-tumor activities of HQP1351 in Patients With GIST or Other Solid Tumors.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: HQP1351 30mg 30 mg QOD(Minor subjects will be enrolled based on weight) |
Drug: HQP1351
HQP1351 Orally, once every other day (QOD) for consecutive 4 weeks each cycle.
|
| Experimental: HQP1351 40mg 40 mg QOD(Minor subjects will be enrolled based on weight) |
Drug: HQP1351
HQP1351 Orally, once every other day (QOD) for consecutive 4 weeks each cycle.
|
| Experimental: HQP1351 50mg 50 mg QOD |
Drug: HQP1351
HQP1351 Orally, once every other day (QOD) for consecutive 4 weeks each cycle.
|
| Experimental: HQP1351 20mg 20 mg QOD (Minor subjects will be enrolled based on weight) |
Drug: HQP1351
HQP1351 Orally, once every other day (QOD) for consecutive 4 weeks each cycle.
|
Outcome Measures
Primary Outcome Measures
- Safety and tolerance [30 days after the last dose of HQP1351]
Patients with HQP1351 treatment related adverse events (AE), serious adverse events (SAE) will be assessed according NCI CTCAE Version 4.03.
Secondary Outcome Measures
- Maximum plasma concentration (Cmax) of HQP1351 on Day 1 and Day 27 post HQP1351 treatment on cycle 1. [28 days]
Pharmacokinetic evaluation
- Area under the plasma concentration versus time curve (AUC) of HQP1351 on Day 1 and Day 27 post HQP1351 treatment on cycle 1. [28 days]
Pharmacokinetic evaluation
- Anti-tumor activities of HQP1351 [3-60 months]
Response will be evaluated every 2 cycles (8 weeks), according to the revised RECIST Guideline, Version 1.1
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Male or not pregnant or lactating women, age≥12years.
-
Advanced and/or metastatic GIST or other solid tumors, confirmed by histology and/or cytology. GIST patients must be primary resistant to imatinib (tumor progresses within 6 months first-line imatinib treatment, or succinate dehydrogenase B (SDHB) deficient confirmed by immunohistochemistry, or NF1 mutation), OR imatinib or imatinib and at least one other TKI treatment failure (after imatinib or other TKI treatment for more than 6 months, tumor progress again after achieving tumor remission or stability).
-
ECOG≤ 2.
-
Estimated survival at least 3 months.
-
Adequate hematologic and bone marrow functions.
-
Adequate renal and liver function.
-
Heart function index:
-
Troponin(I/T) ≤ Upper Limit of Normal;
-
Ejection fraction >40%;
-
QTc interval ≤ 450 ms in male or ≤ 470 ms in female.
-
Negative serum pregnancy test (for women of childbearing potential) documented within the 24-hour prior to the first dose of investigational product.
-
Willing to use contraception by a method that is deemed effective by the investigator by Subject and their partners throughout the treatment period and for at least 30 days following the last dose of study drug.
-
Ability to understand and willingness to sign a written informed consent form (the consent form must be signed by the subject prior to any study-specific procedures).
-
Willing and ability to comply with study procedures and follow-up examination.
Exclusion Criteria:
-
Received any anti-cancer chemotherapy, biological agent treatment (e.g. Monoclonal antibody), immunotherapy (e.g. IFN) or radiotherapy with 28 days or 5 times half- time before first dose of HQP1351.
-
Received any TKIs within 14 days before first dose of HQP1351.
-
Attended any clinical trials on other drugs within 14 days before first dose of HQP1351.
-
Have not recovered (> Grade 1 by CTCAE, v. 4.0) from AEs (except alopecia) due to agents previously administered.
-
Malabsorption syndrome or other diseases that affect the absorption of oral drugs.
-
Cardiovascular diseases of clinical significance, uncontrollable or active, including but not limited to: history of myocardial infarction; unstable history of angina pectoris; a history of congestive heart failure or lower left ventricular ejection fraction (LVEF) than normal limit within 6 months; the history of atrial arrhythmias was judged by the researchers to have important clinical significance; history of ventricular arrhythmias, etc.
-
Hypertension was still poorly controlled after medication treatment (SBP > 140 mmHg and/or DBP > 90 mmHg).
-
Concurrent use any medication led to prolong QT interval.
-
Pulmonary mean arterial pressure>35 mmHg by ECHO.
-
Significant severe cardiovascular conditions during previous TKI treatment.
-
Uncontrollable hypertriglyceridemia.
-
Performed major surgery (except for intravenous catheterization or bone marrow biopsy) within 14 days of first dose of HQP1351.
-
Arterial thrombosis or embolism events such as cerebrovascular accident (including transient ischemic attack, TIA), or venous thrombosis events or pulmonary embolism within 6 months before the first dose of HQP1351 or deep vein thrombosis within 3 months before the first dose of HQP1351.
-
Brain metastasis.
-
Had other primary malignant tumors in the last three years (exception of the tumors being cured for 5 years or more, or complete removal of non-melanoma skin cancer or successful treatment of carcinoma in situ, or the controlled prostate cancer).
-
Had active, symptomatic infections (including known infections of HIV, viral hepatitis (A, B, or C)). If there is no history of infection, screening is not required.
-
Subjects who are known to be allergic to pharmaceutical ingredients or their analogs.
-
Pregnancy or lactation, or expect to be pregnant during the study period.
-
According to the judgment of the investigator or sponsor, any symptoms or disease of the subject may jeopardize the safety or safety assessment of the subject.
-
Any other condition or circumstance of that would, in the opinion of the investigator, make the patient unsuitable for participation in the study.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Sun-Yat Sen University Cancer Center | Guangzhou | Guangdong | China | 510060 |
| 2 | Guangdong general hospital | Guangzhou | Guangdong | China | |
| 3 | Henan cancer hospital | Zhengzhou | Henan | China | |
| 4 | Union Hospital Tongji Medical College of Huazhong University of Science ang Technology | Wuhan | Hubei | China | 215316 |
| 5 | Chinese PLA general hospital, Beijing, China | Beijing | China | ||
| 6 | Fudan University Shanghai Cancer Center | Shanghai | China |
Sponsors and Collaborators
- Ascentage Pharma Group Inc.
- HealthQuest Pharma Inc.
Investigators
- Principal Investigator: Ruihua Xu, Professor, Sun Yat-sen University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- SJ-0003