Gastric cancer
Conditions
Interventions
Treatment group:This study employs a "3+3 dose-escalation design" for pimisertib mesylate, with dose levels escalated sequentially at 3.0 mg/m^2, 4.5 mg/m^2, and 6.0 mg/m^2. Participants in each dose-
Sponsors
West China Hospital, Sichuan University
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Inclusion criteria
Inclusion criteria: 1. The participants are is voluntary to participate in the clinical trial; the participants fully understand and are informed of the study and sign the informed consent form; the participants are willing to follow and be able to complete all trial procedures; 2. Aged between 18 and 70, open to both males and females; 3. Patients with pathologically confirmed unresectable locally advanced or metastatic gastric/ gastroesophageal junction adenocarcinoma; 4. Subjects who have previously received at least two treatment regimens for advanced or metastatic disease, if three chemotherapy drugs including taxanes (or anthracyclines), platinum compounds, and fluoropyrimidines were used as first-line treatment, these patients may also be eligible for enrollment in the study as assessed by the investigator; subjects with HER2-positive disease should have failed standard HER2-targeted therapy; Note: (1) Progress within 6 months after previous adjuvant or neoadjuvant chemotherapy is considered equivalent to disease progression during first-line treatment for advanced or metastatic disease; (2) If a drug in the previous combination therapy regimen was discontinued due to AEs, while the other drugs remained in use, it should be considered as "the same previous treatment regimen"; (3) If previous treatment was terminated due to poor tolerance or AEs, but no disease progression was recorded, it is not considered as "having received a previous treatment regimen"; (4) Changes in the dosage or route of administration of previous treatment regimens (such as IV or oral fluoropyrimidines) should be considered as "the same previous treatment regimen" if they are not accompanied by disease progression; 5. Expected survival duration >= 12 weeks; 6. There is measurable tumor lesion according to RECIST 1.1 criteria; (1) If a lesion that has previously undergone radiotherapy has progressed after the most recent radiotherapy and its boundary is clear, it can be considered as a target lesion; (2) For subjects who undergo biopsy during screening and/or treatment, although it is not required, the biopsy lesion should ideally be different from any target lesion used for RECIST 1.1 evaluation; 7. ECOG performance status score of 0-1, with no deterioration occurring within 2 weeks prior to baseline or the first day of drug administration; 8. Adequate organ and bone marrow function, with laboratory test values meeting the following requirements within 7 days prior to enrollment (no blood components, cell growth factors, albumin, or other corrective medications are allowed within 14 days prior to obtaining laboratory test results), as detailed below: (1) Complete blood count: absolute neutrophil count (ANC) >=1.5×10^9/L; platelet count (PLT) >=100×10^9/L; hemoglobin (HGB) >=9.0 g/dL; (2) Liver function: Total bilirubin (TBIL) = 30g/L; (3) Renal function: serum creatinine (Cr) <=1.5×ULN; (4) Coagulation function: International normalized ratio (INR) <= 1.5×ULN, and activated partial thromboplastin time (APTT) <= 1.5×ULN; 9. Female subjects of childbearing age or male subjects whose sexual partners are female subjects of childbearing age must take effective contraceptive measures throughout the treatment period and for six months thereafter
Exclusion criteria
Exclusion criteria: 1. Pregnant or lactating women; 2. Individuals infected with the Human Immunodeficiency Virus (HIV) (HIV 1/2 antibody positive), and individuals with known syphilis infection (TPPA test positive); 3. Any uncontrollable active infection, including but not limited to active tuberculosis; individuals who are currently undergoing anti-tuberculosis treatment or have received anti-tuberculosis treatment within 1 year prior to the first dose; 4. Known to have interstitial lung disease requiring steroid hormone treatment; 5. Known to have acute or chronic active hepatitis B (HBsAg positive and HBV DNA >= 2000 IU/mL or >= 10^4 copies/mL) or acute or chronic active hepatitis C (HCV antibody positive and HCV RNA positive) ; 6. Subjects with clinically significant thyroid dysfunction (as determined by serum thyroid hormone tests including TT4, TT3, FT3, FT4, and serum thyroid-stimulating hormone (TSH)) were deemed ineligible for enrollment in the study; 7. The toxic side effects caused by previous treatment have not recovered to CTCAE grade <=1. For adverse reactions such as hair loss and hypothyroidism, if they are tolerable as judged by the investigator or the laboratory test abnormalities are allowed in this study, can be excluded; 8. Previously exposed to any HDAC inhibitor; 9. Participating in another interventional clinical study at the same time, unless participating in observational (non-interventional) clinical studies or in the follow-up phase of an interventional study; 10. Having received anti-tumor treatment for the study disease within 3 weeks before the first dose, including but not limited to surgical operation, systemic chemotherapy (or within 5 half-lives of the drug, whichever is shorter), intervention, etc., or having received radiotherapy within 4 weeks before the first dose; or having received other unlisted clinical research drugs within 4 weeks (or within 5 half-lives of the drug, whichever is shorter) ; 11. Have used immunosuppressive drugs within 4 weeks before the first dose, excluding topical glucocorticoids administered via nasal spray, inhalation, or other routes, or systemic glucocorticoids at physiological doses (i.e., not exceeding 10 mg/day of prednisone or equivalent doses of other glucocorticoids) ; 12. Having received or planning to receive attenuated live vaccines within 4 weeks during the study period; 13. Active autoimmune disease requiring systemic treatment (such as disease-modifying drugs, corticosteroids, or immunosuppressants) within 2 years before the first dose. Alternative therapies (such as thyroxine, insulin, or physiological corticosteroids for adrenal or pituitary insufficiency) are allowed. Known history of primary immunodeficiency. Patients with only positive autoimmune antibodies need to be confirmed by the investigator whether they have autoimmune disease; 14. Having suffered from other unhealed malignant tumors within the past 3 years or currently suffering from such tumors, except for tumors with very low malignancy such as cervical cancer in situ and basal cell carcinoma of the skin; 15. Hepatic encephalopathy, hepatorenal syndrome, or Child-Pugh B grade or more severe cirrhosis; 16. Known or suspected brain metastasis; 17. Known history of hereditary bleeding tendency or coagulation dysfunction; 18. Pleural effusion, ascites, and pericardial effusion with clinical symptoms or requiring drainage, except for cases where imaging only shows a small amount of pleural effusion, a small amount of
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose limiting toxicity (DLT);Safety;Recommended phase 2 dose (RP2D); | — |
Secondary
| Measure | Time frame |
|---|---|
| Maximum tolerated dose (MTD);Objective response rate (ORR);Disease control rate (DCR);Progression-free survival (PFS);Overall survival (OS); | — |
Countries
China
Contacts
Public ContactHu Jiankun
West China Hospital, Sichuan University
Outcome results
None listed