None listed
Conditions
Brief summary
This study aims to establish the safety and best tolerated dose of a new investigational drug called APG-1387 in participants with advanced cancer. Who is it for? You may be eligible to join this study if you are aged 18 years or more and have been diagnosed with an advanced solid tumour or lymphoma. Study details All participants in this study will be treated with a new investigational drug called APG-1387. This drug blocks tumour growth by promoting cell death (a process called apoptosis) in cancer cells and attempts to stop the cancer cells from spreading further throughout the body. This drug has not previously been tested in humans. APG-1387 has undergone extensive testing in various animal models (including rats and monkeys) and human cancer cell models in the laboratory. APG-1387 will be administered via intravenous (IV) infusion (i.e. directly into the vein) on Days 1, 8 and 15 of study participation. The first group of participants will receive a dose of 0.3 mg of APG-1387, and if tolerated the dose will be increased for subsequent patient groups. Participants will be regularly monitored until they reach their 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-center, single-agent, open-label, Phase I accelerated dose escalation study of APG-1387. Initially, single patient cohorts will be evaluated and doses of APG-1387will increase by 50% until = Grade 2 drug related toxicity is observed, at which point dose escalation and cohort rules will follow a modified Fibonacci 3/6 Phase I design. Allowances for intra-patient dose escalations are provided. Treatment cycles will begin at 0.3 mg of APG-1387 administered via intravenous infusio
This is a multi-center, single-agent, open-label, Phase I accelerated dose escalation study of APG-1387. Initially, single patient cohorts will be evaluated and doses of APG-1387will increase by 50% until = Grade 2 drug related toxicity is observed, at which point dose escalation and cohort rules will follow a modified Fibonacci 3/6 Phase I design. Allowances for intra-patient dose escalations are provided. Treatment cycles will begin at 0.3 mg of APG-1387 administered via intravenous infusion for 30 minutes on Days 1, 8 and 15, then take one–week treatment off; each dosing cycle is 28 days. Doses could be modified depending on toxicity and PK results based on discussions with the Investigators and Sponsor. If no DLTs are observed by the end of Cycle 1, the dose of APG-1387 will be increased in subsequent cohorts, at 0.6 mg, 1 mg, 1.5 mg, 2.5 mg, 4.0 mg, 7.0 mg, 12 mg, 20 mg and 30 mg accordingly. Patients will be treated with APG-1387 until disease progression, unacceptable toxicity occurs or the patient withdraws consent.
Sponsors
Jiangsu Ascentage Pharma Inc
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
-Histologically or cytologically confirmed solid tumor or lymphoma; -Male or non-pregnant, non-lactating female patients age greater than or equal to 18 years; -Locally advanced or metastatic disease for which no standard therapy is judged appropriate by the investigator; -Life expectancy greater than or equal to 3 months; -Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to 1; -Adequate hematologic function as indicated by: ANC greater than or equal to 1,500/mm3; Hemoglobin greater than or equal to 9.0 g/dL; platelet count greater than or equal to 100,000/mm3 -QTc interval less than or equal to 450ms -Adequate renal and liver function as indicated by: -Serum creatinine less than or equal to 1. x ULN or if serum creatinine is >1.5 X ULN, creatinine clearance of greater than or equal to 50 cc/min; total bilirubin less than or equal to 1.5 x ULN AST and ALT less than or equal to 2.5 x ULN ; Alkaline phosphatase less than or equal to 2.5 x ULN -Negative Hepatitis B and Hepatitis C screening: -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 one month 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 patient prior to any study-specific procedures; -Willingness and ability to comply with study procedures and follow-up examination.
Exclusion criteria
-Received chemotherapy within 21 days (42 days for nitrosoureas or mitomycin C) prior to entering the study; Received hormonal, biologic therapies (e.g. interferons), or therapeutic antibodies (e.g. trastuzumab, cetuximab, rituximab, etc) within 21 days or <4 half-lives (whichever is greater) of study entry; Note: Leuteinizing hormone-releasing hormone (LHRH) agonists or antagonists to maintain castrate levels of testosterone in patients with hormone-refractory prostate cancer is allowed. Oral contraceptives and estrogen/progestogen HRT are acceptable -Receiving concurrent anti-cancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy, hormonal therapy, targeted therapy, biologic therapy); or has had tumor embolization within 14 days of study entry. -Radiation within 14 days of study entry, thoracic radiation within 28 days of study entry. Patients who have received prior radiotherapy must have discontinued steroids for 14 days prior to study entry and be clinically stable; -Failure to recover to less than or equal to Grade 1 from adverse events due to radiotherapy or chemotherapy agents; -Requirement for corticosteroid treatment, with the exception of megestrol, topical corticosteroids and inhaled corticosteroids for reactive airway disease. Patients who received prior therapy with corticosteroids must have discontinued use of corticosteroid therapy 14 days prior to the first dose of APG-1387 ; The patients who require replacement dose corticosteroids are allowed (eg if they have had endocrinopathy from ipilimumab) -Use of therapeutic doses of anti-coagulants is excluded. Therapeutic is defined as a target International Normalized Ratio (INR) of 1.5 or above. However, the prophylactic dose anticoagulation is allowed. -Concurrent treatment with an investigational agent or device within 28 days prior to the first dose of therapy; -Failure to recover adequately, as judged by the investigator, from prior surgical procedures. Patients with active wound healing, 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; -Elevated (above institutional normal limits) serum troponin T or I. -Unstable angina, myocardial infarction, or a coronary revascularization procedure within 180 days of study entry. -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; -History of Bell’s palsy -Active rheumatoid arthritis (RA), active inflammatory bowel disease, chronic infections, or any other disease or condition associated with chronic inflammation; -Active symptomatic fungal, bacterial and/or viral infection including, but not limited to, active HIV or viral hepatitis (A, B or C); -Known or suspected Wilson's Disease, or other conditions that affect copper accumulation or regulation. -Uncontrolled concurrent illness including, but not limited to: serious uncontrolled infection, symptomatic congestive heart failure (CHF), unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with the study requirements. -Prior treatment with IAP inhibitors. -Any other condition or circumstance that would, in the opinion of the investigator, make the patient unsuitable for participation in the study.
Outcome results
None listed