- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03080311
A Study of APG-1252 in Patients With SCLC or Other Solid Tumors
A Phase I Study of the Safety, Pharmacokinetic and Pharmacodynamic Properties of Intravenously Administered APG-1252 in Patients With Small Cell Lung Cancer (SCLC) or Other Solid Tumors
APG-1252 is a highly potent Bcl-2 family protein inhibitor, a promising drug candidate which shown high binding affinities to Bcl-2, Bcl-xL and Bcl-w. The preclinical studies have shown that APG-1252 alone achieves complete and persistent tumor regression in multiple tumor xenograft models with a twice weekly or weekly dose-schedule, including SCLC, colon, breast and acute lymphocytic leukemia (ALL) cancer xenografts; achieves strong synergy with the chemotherapeutic agents, indicating that APG-1252 may have a broad therapeutic potential for the treatment of human cancer as a single agent and in combination with other classes of anticancer drugs. APG-1252 is intended for the treatment of patients with SCLC or other solid tumors.
This is a multi-center, open-label, dose escalation Phase I study to determine the MTD and DLTs of intravenously administered APG-1252. After dose escalation to 240mg twice weekly, 2 dose cohorts two different dosing schedules including weekly and twice weekly will be assessed to evaluate for safety, tolerability, pharmacokinetics (PK) and preliminary anti-tumor efficacy. Treatment with APG-1252 will be administered to 30-60 patients at approximately 2 investigational sites in US.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
In dose cohort 1, patients will be treated in cycles, which are defined by APG-1252 intravenous administration on Days 1, 4, 8, 11, 15, 18 and 22, over a 28-day cycle the start dose is 10mg.
After dose escalation to 240mg twice weekly in dose cohort 1, dose cohort 2 will be performed with dose cohort 1 parallelly, patients will be treated in the same 28-day-cycles, APG-1252 intravenous administration on Days 1, 8, 15, and 22, the start dose is 240mg.
In both dose cohorts' patients could continue to receive cycles of APG-1252 until disease progress or unacceptable toxicity.
Study drug will be administered by intravenous infusion for 30 minutes at the investigational site by site staff.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Michigan
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Grand Rapids, Michigan, United States, 49503
- START Midwest
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Texas
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San Antonio, Texas, United States, 78229
- The START Center for Cancer Care
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Histologically or cytologically confirmed small cell lung cancer (SCLC) or other solid tumors
- Male or non-pregnant, non-lactating female patients age ≥18 years
- Locally advanced or metastatic disease for which no standard therapy is judged appropriate by the investigator
- Eastern Cooperative Oncology Group (ECOG) Performance Status < 2
Adequate hematologic function as indicated by:
- Platelet count ≥ 100,000/mm˄3
- Hemoglobin ≥ 9.0g/dL Platelet count ≥ 100,000/mm˄3
- Absolute neutrophil count (ANC) ≥1000/µL
Adequate renal and liver function as indicated by:
- Serum creatinine ≤ 1.5 x upper limit of normal (ULN); if serum creatinine is >1.5 X ULN, creatinine clearance must be ≥ 50 mL/min
- Total bilirubin ≤1.5 x ULN; If Gilbert's Syndrome may have Bilirubin> 1.5 x ULN
- Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤3 x ULN of institution's normal range; for patients with known liver metastases, AST and ALT may be ≤ 5 x ULN
- Coagulation: activated partial thromboplastin time (aPTT) and prothrombin time (PT)<1.2 x the upper limit of normal
- Brain metastases with clinically controlled neurologic symptoms, defined as surgical excision and/or radiation therapy followed by 21 days of stable neurologic function and no evidence of CNS disease progression as determined by CT or MRI within 21 days prior to the first dose of study drug
- 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
- Ability to understand and willingness to sign a written informed consent form
- Willingness and ability to comply with study procedures and follow-up examination
Exclusion Criteria:
- 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
- Steroid therapy for anti-neoplastic intent within 7 days prior to the first dose of study drug
- Continuance of toxicities due to prior radiotherapy or chemotherapy agents that do not recover to < Grade 2
- Known bleeding diathesis/disorder
- Recent history of non-chemotherapy induced thrombocytopenia associated bleeding within 1 year prior to first dose of study drug
- 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)
- Serious gastrointestinal bleeding within 3 months
- Use of therapeutic doses of anti-coagulants is excluded, along with anti-platelet agents; low-dose anticoagulation medications that are used to maintain the patency of a central intravenous catheter are permitted
- Received a biologic (G-CSF, GM-CSF or erythropoietin) within 28 days prior to the first dose of study drug
- 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
- 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
- Active symptomatic fungal, bacterial and/or viral infection including, but not limited to, active human immunodeficiency virus (HIV) or viral hepatitis (B or C)
- Diagnosis of fever and neutropenia within 1 week prior to study drug administration
- Uncontrolled concurrent illness including, but not limited to: serious uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with the study requirements
- Prior treatment with Bcl-2/Bcl-xL inhibitors
- Any other condition or circumstance of that would, in the opinion of the investigator, make the patient unsuitable for participation in the study
- Known clinically active hepatitis B or hepatitis C infection. Testing for hepatitis B and C is not required for study enrollment.
- Known HIV infection
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: APG-1252
An accelerated dose escalation scheme will be utilized initially with one patient enrolled per cohort.
If at 10 mg or 20 mg dose level, any occurrence in cycle 1 of one ≥ Grade 2 adverse event related or possibly related to APG-1252 (graded as per the National Cancer Institute's Common Terminology Criteria for Adverse Events [NCI CTCAE] version 4.0) is the trigger for converting to a standard 3+3 design at that dose level.
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Multiple dose cohorts, 30 minute IV infusion, twice weekly for 3 weeks of a cycle with 28 days.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Dose limiting toxicity (DLT) determination
Time Frame: 28 days
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Number of participants with APG-1252 treatment-related adverse events as assessed by NCI CTCAE v4.03
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28 days
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Maximum tolerated dose (MTD) determination
Time Frame: 18 - 24 months
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If ≥ 2/6 patients develop a DLT at any dose level, then this dose will be declared as the MTD
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18 - 24 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Pharmacokinetic evaluation
Time Frame: 18 - 24 months
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Peak plasma concentration (Cmax) will be assessed on all participants with APG-1252 treatments
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18 - 24 months
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Pharmacokinetic evaluation
Time Frame: 18 - 24 months
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Area under the plasma concentration versus time curve (AUC) will be assessed on all participants with APG-1252 treatments
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18 - 24 months
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Pharmacodynamic evaluation
Time Frame: 18-24 months
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Platelet counts will be measured on the participants with APG-1252 treatments
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18-24 months
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Pharmacodynamic evaluation
Time Frame: 18-24 months
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Bcl-2 protein in peripheral blood mononuclear cells (PBMCs) will be measured on the participants with APG-1252 treatments
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18-24 months
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Pharmacodynamic evaluation
Time Frame: 18-24 months
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Activation of apoptosis will be measured on the participants with APG-1252 treatments
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18-24 months
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Preliminary efficacy assessment
Time Frame: 18-24 months
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Patients will be evaluated for response every 2 cycles (i.e., 8 weeks), according to the new response evaluation criteria in solid tumors: revised RECIST Guideline, Version 1.1
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18-24 months
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- APG-1252-US-001
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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