None listed
Conditions
Brief summary
This study aims to establish the safety and best tolerated dose of a new investigational drug called APG-2449 in participants with ovarian cancer. Who is it for? You may be eligible to join this study if you are aged greater or equal to 18 years and have been diagnosed with ovarian cancer. Study details: All participants in this study will be treated with a new investigational drug called APG-2449 in combination with a chemotherapy called Doxorubicin Hydrochloride Liposome (PLD). APG-2449 capsules will be administered to study participants orally once daily at a 28-day repeated cycles, 1200mg as the starting dose, and the dose level may be escalated to 1500mg or de-escalated to 900mg to determine the optimal dose level based on the safety observations, in combination with PLD 40mg/m2 intravenously infused on Day 1 of each 28-day cycle. More participants will be treated, once the optimal dose level of APG2449 identified, with APG2449 capsules orally daily in combination with PLD 40mg/m2 intravenously infused on Day 1 of each 28-day cycle. Participants will be closely monitored until they reach their study endpoint (disease progression, intolerable toxicity or withdrawal of consent) in order to determine safety, tolerability and preliminary efficacy of treatment. The results from this study will be analysed to see if it is worthwhile for this new drug to be tested in future studies involving larger numbers of cancer participants.
Interventions
This is a multi-centre, open-label study of APG-2449 combined with Doxorubicin Hydrochloride Liposome (PLD) to evaluate the safety and efficacy in patients with ovarian cancer.
APG-2449 capsules will be administered orally on Day 1 of Cycle 1, and then once daily from Day 4 of Cycle 1 on a 28-day repeated cycles, 1200mg as the starting dose, following the principle of 3+3 study design to determine the safety of the combination/RP2D of the combination, and the dose escalation or de-escalation wi
This is a multi-centre, open-label study of APG-2449 combined with Doxorubicin Hydrochloride Liposome (PLD) to evaluate the safety and efficacy in patients with ovarian cancer. APG-2449 capsules will be administered orally on Day 1 of Cycle 1, and then once daily from Day 4 of Cycle 1 on a 28-day repeated cycles, 1200mg as the starting dose, following the principle of 3+3 study design to determine the safety of the combination/RP2D of the combination, and the dose escalation or de-escalation will be performed based on the safety of the starting dose. The escalated dose will be 1500 mg and the de-escalated dose will be 900 mg. PLD 40 mg/m2 is intravenously infused on Day 4 of Cycle 1 and then Day 1 of each subsequent 28-day cycles. Patient will be continuously treated until disease progression, unacceptable toxicity, or other criteria for treatment discontinuation are met, whichever comes first. No intra-patient dose escalation will be allowed. Once the RP2D is determined, expansion study cohort will be enrolled to assess the efficacy and safety of APG-2449/PLD combination in treating patients with platinum-resistant ovarian cancer. Specifically, APG-2449 will be administered at the RP2D orally daily for 28 days in each treatment cycle, in combination with PLD 40 mg/m2 intravenously infused on Day 1 of each 28-day cycle. Patient will be continuously treated until disease progression, unacceptable toxicity, or other criteria for treatment discontinuation are met, whichever comes first. Throughout the study, compliance and safety of the participants will be closedly monitored via regular medical review, safety lab assessments, drug administration diary and timely reconciliation of returned pills, etc.
Sponsors
Ascentage Pharma Pty Ltd
Study design
Allocation
Non-randomised trial
Intervention model
Other
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Patients must meet all the following inclusion criteria to be eligible for participation in this study: 1. greater than or equal to 18 years of age 2. Histologically confirmed ovarian cancer, including fallopian tube cancer, or primary peritoneal cancer, especially the subtype high-grade serous ovarian cancer (HGSOC). 3. Prior treatment with a platinum-based regimen and disease progression or relapse during platinum-based regimen therapy (at least 4 cycles) or within 6 months (184 calendar days) of the last platinum therapy. Note: Progression or recurrence of disease requires evidence of radiographic or clinical progression (e.g. cytological reports of new ascites or pleural effusion). Primary platinum-refractory (defined as progression during or within 4 weeks post to the first platinum-containing regimen) subjects could not be enrolled, but secondary platinum-refractory subjects could be enrolled in the study without the requirement for at least 4 cycles of platinum containing therapy. 4. Up to 5 lines of prior systemic therapies are permitted; up to 2 lines of prior systemic therapy are permitted following diagnosis of platinum-resistant relapse. Note: Hormone therapy (eg, tamoxifen), maintenance therapy with PARP inhibitors and bevacizumab are not counted as treatment lines. Other special maintenance options may not be counted as treatment lines. 5. Presence of at least one measurable tumor lesion (as assessed by the investigator) according to RECIST 1.1 criteria. 6. Eastern Cooperative Oncology Group (ECOG) score 0 to 1. 7. Life expectancy at least 3 months. 8. Adequate bone marrow, liver, kidney, and coagulation function reserve as confirmed by laboratory tests within 3 days prior to the first dose. a) Hemoglobin (Hb) greater than or equal to 90 g/L independent of transfusion red blood cell transfusion and erythropoietin (EPO) use. b) Platelet count greater than or equal to 100 x 10^9/L and independent of platelet transfusion. c) Absolute neutrophil count (ANC) greater than or equal to 10^9/L and independent of the use of colony-stimulating factor (CSF). d) Total bilirubin less than or equal to 1.5×upper limit of normal (ULN). e) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to 2.5×ULN (less than or equal to 5× ULN for subjects with confirmed liver metastases). f) Albumin greater than or equal to 30 g/L. g) Serum creatinine less than or equal to 1.5×ULN, and if serum creatinine greater than 1.5×ULN, creatinine clearance greater than or equal to 50 mL/min calculated using the Cockcroft-Gault formula. h) Negative or weakly positive urine protein (±); or urine protein 1 + but 24-hour urine protein quantification less than 1.0g/24 h. i) International normalized ratio (INR) less than or equal to 1.5 and activated partial thromboplastin time (aPTT) less than or equal to 1.5×ULN. Subjects on stable anticoagulant therapy may be enrolled at the discretion of the investigator. 9. AEs caused by previous treatment must be recovered to Grade 1 (CTCAEv5.0) or stable state as assessed by the investigator. Note: Mild toxicities without safety concerns, such as alopecia and grade 2 neuralgia, may be included at the investigator 's discretion. 10. Female subjects must be non-pregnant and non-lactating and meet either of the following: a) Does not meet the definition of women of childbearing potential (WOCBP). Or b) WOCBP agrees to comply with the contraception guidelines during the treatment period and for 3 months following the last dose. 11. Willing to sign an informed consent form. Voluntary written informed consent must be obtained from the subject before any study-specific procedures are performed, unless the procedures are performed according to clinical criteria and fall within the protocol-required time window and meet study-specific requirements, such as tumor imaging.
Exclusion criteria
Patients who meet any of the following exclusion criteria are not to be enrolled in this study: 1. Major surgery or major trauma within 28 days prior to the first dose or diagnostic biopsy within 14 days prior to the first dose. Note: Patients who are expected to require major surgery during study treatment will also be excluded. Subjects who had a diagnostic biopsy within 14 days prior to the first dose could also be enrolled if the investigator judged that the diagnostic biopsy did not affect the efficacy assessments during the study. 2. Have received systemic antineoplastic agents including investigational agents within a specified period, including targeted therapy within 14 days or 5 half-lives (whichever is shorter) before the first dose, or immunotherapy within 28 days before the first dose. 3. Radiotherapy within 14 days prior to first dose. 4. Previous FAK inhibitors 5. Previous cumulative anthracycline dose greater than or equal to 550 mg/m2. 6. Other sites or other histological types of tumors other than existing ovarian cancer within 3 years before the first dose, except curable tumors such as cervical carcinoma in situ. 7. Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Note: Subjects may be considered for enrollment if they have previously treated brain metastases that are clinically stable or radiologically stable within 14 days prior to the first dose (confirmed by repeat imaging at least 4 weeks apart and performed at screening). 8. Major cardiovascular or cerebrovascular disease (such as congestive heart failure, acute myocardial infarction, unstable angina pectoris, stroke, transient ischemic attack, deep venous thrombosis) within 6 months before the first dose, or any of the following abnormalities: a) QTc interval greater than 480 milliseconds. b) Left ventricular ejection fraction (LVEF) less than 50%. c) New York Heart Association (NYHA) cardiac function classification greater than or equal to grade 2. d) Severe arrhythmia. e) Poorly controlled hypertension or diabetes. f) Other serious heart disease. 9. Clinical symptoms of pleural effusion, pericardial effusion, or ascites should need puncture, drainage or drainage within 1 month before the first dose, except for a small amount of effusion on imaging but not accompanied by clinical symptoms. 10. Presence of malabsorption syndrome, or inability to take oral medication, or bowel obstruction. 11. Presence of serious gastrointestinal disease such as poorly controlled gastrointestinal inflammatory disease (active Crohn 's disease or ulcerative colitis) or poorly controlled gastrointestinal bleeding. Presence of clinical or radiographic evidence of ileus, or etiology of previous recurrent ileus will not be excluded. 12. Uncontrolled or active infectious diseases such as HIV, hepatitis B and hepatitis C. 13. Systemic administration of moderate or strong inhibitors/inducers of CYP3A4, CYP2C9 or CYP2C19 within 7 days prior to the first dose. Systemic administration of CYP3A4 sensitive substrates with narrow therapeutic index within 7 days prior to the first dose. 14. Other factors may cause the subject to be forced to terminate the study halfway as judged by the investigator, such as having other serious diseases (including mental illness) requiring concomitant treatment, severely abnormal laboratory tests, family, or social factors, which may affect the safety of the subject or the collection of trial data, etc.
Outcome results
None listed