None listed
Conditions
Brief summary
The primary purpose of this study is to evaluate the safety of a new cancer drug, APG-1252 which has not yet been tested in humans. The study will also look at the amount of drug in the blood to evaluate the way the body processes the drug and the way the drug acts on the growth of tumours in cancer patients. Who is it for? You may be eligible to participate in this study if you are aged 18 or over, and have been diagnosed with Small cell lung cancer or other solid tumor types with no standard treatment options. Before the study starts, they are asked to sign a consent form. Each participant then goes through a series of tests to see whether the study is suitable for them. These tests include reviewing the participants medical and medication history, a physical examination, an electrocardiogram (ECG), CT and bone scans (to locate and measure tumours), taking urine and blood samples for testing and asking about how able they are to do their usual daily activities. If a participant's test results are satisfactory, they are enrolled into the study. Study details: All participants in this study will receive a specified dose of APG-1252 in 28-day cycles, which is administered intravenously (i.e. directly into the vein), at a starting dose of 10mg. The first set of participants will start on the lowest dose level, with the next highest dose only commencing in the next set of participants once the safety of the first dose has been confirmed. Researchers will take a number of blood samples on days 1, 3, 8, 15, 22 of dosing in each participant to examine the rate that the body processes the drug. Further blood samples, as well as CT, MRI scans other medical imaging/assessments will be taken before treatment and at the end of treatment to look for changes in tumour growth. Participants will also be assessed for side effects throughout the study period. It is hoped that the findings of this trial will show whether APG-1252 can be safely given to cancer patients, and provide information on the rate of processing of the drug in the body. Using this information, researchers hope to find the best dose to use for further testing of APG-1252 in cancer patients.
Interventions
Investigational product will be administered via intravenous infusion for 30 minutes. No investigational or commercial agents or therapies may be administered with the intent to treat the patient's malignancy other than APG-1252. Supportive care measures including those directed at controlling symptoms resulting from the patient’s malignancy are allowed. Patients will be treated in 28-day cycles. Treatment will begin in the first cycle at 10 mg of APG-1252 administered via intravenous infusion f
Investigational product will be administered via intravenous infusion for 30 minutes. No investigational or commercial agents or therapies may be administered with the intent to treat the patient's malignancy other than APG-1252. Supportive care measures including those directed at controlling symptoms resulting from the patient’s malignancy are allowed. Patients will be treated in 28-day cycles. Treatment will begin in the first cycle at 10 mg of APG-1252 administered via intravenous infusion for 30 minutes, twice weekly (on Days 1, 4, 8, 11, 15, 18 and 22 of each cycle), then will be one week off treatment before commencing the next treatment cycle. Doses can be modified depending on toxicity and PK results based on discussions with the Investigators and Sponsor. If no DLTs or less than two drug related Grade 2 toxicities are observed by the end of Cycle 1, the dose of APG-1252 will be increased in subsequent cohorts, to 80 mg, 120 mg, 240 mg, 320 mg and 400 mg accordingly. If a DLT or two drug related Grade 2 toxicities occur in Cycle 1 at any dose level escalation will convert to the standard 3+3 design and will occur at increments of 1.4 x the preceding dose. If greater than or equal to 2/6 patients develop DLT at any dose level dose escalation will cease and the dose level immediately below will be expanded to 6 patients. If less than or equal to 1/6 patients develop a DLT at the highest dose reached this will be declared the MTD.
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 of the following inclusion criteria to be eligible for participation in this study: 1. Histologically or cytologically confirmed small cell lung cancer (SCLC) or other solid tumors; 2. Male or non-pregnant, non-lactating female patients age of 18 years or above; 3. Locally advanced or metastatic disease for which no standard therapy is judged appropriate by the investigator; 4. Eastern Cooperative Oncology Group (ECOG) Performance Status equal to or less than 2; 5. Adequate hematologic function as indicated by: a. Platelet count greater than or equal to 100,000/mm3, Note: Use of transfusions or thrombopoietic agents to achieve baseline platelet count criterion is prohibited. b. Absolute neutrophil count (ANC) greater than or equal to 1000/micro litre Note: Use of growth-factors to maintain ANC criterion is not permitted. c. Hemoglobin greater than or equal to 9.0g/dL 6. Adequate renal and liver function as indicated by: a. Serum creatinine less than or equal to 2.0mg/dL or calculated creatinine clearance greater than or equal to 50mL/min; b. Total bilirubin less than or equal to 1.5 x ULN; If Gilbert's Syndrome may have Bilirubin greater than or equal to 1.5 x ULN c. Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) less than or equal to 3 x ULN of institution's normal range; AST and ALT may be less than or equal to 5 x ULN for patients with known liver metastases. d. Coagulation: aPTT and PT less than or equal to 1.2 x the upper limit of normal 7. Brain metastases with clinically controlled neurologic symptoms, defined as surgical excision and/or radiation therapy followed by 21 days of stable neurologic function & no evidence of CNS disease progression as determined by CT or MRI within 21 days prior to the first dose of study drug. 8. Willingness to use contraception by a method that is deemed effective by the investigator by both males and female patients of child bearing potential (postmenopausal women must have been amenorrheal for at least 12 months to be considered of non-childbearing potential) and their partners throughout the treatment period and for at least three months following the last dose of study drug; 9. Ability to understand and willingness to sign a written informed consent form (the consent form must be signed by the patient prior to any study-specific procedures); 10. Willingness and ability to comply with study procedures and follow-up examination.
Exclusion criteria
Patients who meet any of the following exclusion criteria are not to be enrolled in this study: 1. Receiving concurrent anti-cancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy, hormonal therapy, targeted therapy, biologic therapy, with the exception of hormones for hypothyroidism or estrogen replacement therapy (ERT), anti-estrogen analogs, agonists required to suppress serum testosterone levels); or any investigational therapy, or has had tumor embolization or tumor lysis syndrome (TLS) within 14 days prior to the first dose of study drug. 2. Steroid therapy for anti-neoplastic intent within 7 days prior to the first dose of study drug. 3. Continuance of toxicities due to prior radiotherapy or chemotherapy agents that do not recover to < Grade 2; 4. Known bleeding diathesis/disorder; 5. Recent history of non-chemotherapy induced thrombocytopenia associated bleeding within 1 year prior to first dose of study drug. 6. Have active immune thrombocytopenic purpura (ITP), active autoimmune hemolytic anemia (AIHA), or a history of being refractory to platelet transfusions (within 1 year prior to the first dose of study drug). 7. Serious gastrointestinal bleeding within 3 months. 8. Use of therapeutic doses of anti-coagulants is excluded, along with anti-platelet agents; lowdose anticoagulation medications that are used to maintain the patency of a central intravenous catheter are permitted. 9. Received a biologic (G-CSF, GM-CSF or erythropoietin) within 28 days prior to the first dose of study drug. 10. Failure to recover adequately, as judged by the investigator, from prior surgical procedures. Patients who have had major surgery within 28 days from study entry, and patients who have had minor surgery within 14 days of study entry; 11. Unstable angina, myocardial infarction, or a coronary revascularization procedure within 180 days of study entry. 12. Neurologic instability per clinical evaluation due to tumor involvement of the central nervous system (CNS). Patients with CNS tumors that have been treated, are asymptomatic and who have discontinued steroids (for the treatment of CNS tumors) for >28 days may be enrolled; 13. Active symptomatic fungal, bacterial and/or viral infection including, but not limited to, active human immunodeficiency virus (HIV) or viral hepatitis (B or C); testing for hepatitis B and C is not required for study enrollment. 14. Diagnosis of fever and neutropenia within 1 week prior to study drug administration. 15. Uncontrolled concurrent illness including, but not limited to: serious uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric llness/social situations that would limit compliance with the study requirements. 16. Prior treatment with Bcl-2/Bcl-xL inhibitors. 17. Any other condition or circumstance of that would, in the opinion of the investigator, make the patient unsuitable for participation in the study.
Outcome results
None listed