A study of the safety, pharmacokinetic and pharmacodynamic properties of a novel anticancer drug APG-1252 in patients with small cell lung cancer or other solid tumors
- Conditions
- Solid tumourSmall cell lung cancerCancer - Lung - Small cellCancer - Other cancer types
- Registration Number
- ACTRN12616001597482
- Lead Sponsor
- Ascentage Pharma Pty Ltd
- Brief Summary
Overall, there were no major safety concerns of APG-1252 monotherapy up to 240 mg in patients with small cell lung cancer and other advanced solid tumors. Although there was no significant efficacy signal, we observed tumor cell death induced by APG-1252 treatment. Combination of APG-1252 with other medications will be further investigated in future clinical trials.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 24
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.
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.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method To characterize the safety of APG-1252, when intravenously administered to patients with small cell lung cancer (SCLC) or other solid tumors. All the patients will be monitored by performing and assessing the vital signs, ECG, serum chemistry, full blood examination, coagulation and urinalysis at screening, day1, day2, day 8, day 15 and day 22 of cycle 1, and day 1, day 22 for the subsequent cycles, end of study, and 30 days after last dose.[Baseline screening, cycle 1: day1, day2, day 8, day 15 and day 22; subsequent cycle(s): day 1 and day 22, end of the study, and 30 days after the last dose.];To determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT), when intravenously administered to patients with small cell lung cancer (SCLC) or other solid tutors. DLTs are assessed and determined as per NCI CTCAE v4.0.[End of each treatment cycle.]
- Secondary Outcome Measures
Name Time Method