A Study of APG-1252 in Patients With SCLC or Other Solid Tumors
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|ClinicalTrials.gov Identifier: NCT03080311|
Recruitment Status : Recruiting
First Posted : March 15, 2017
Last Update Posted : March 15, 2019
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 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, PK and preliminary anti-tumor efficacy. Treatment with APG-1252 will be administered to 30-60 patients at approximately 2 investigational sites in US.
|Condition or disease||Intervention/treatment||Phase|
|Small Cell Lung Cancer and Other Solid Tumors||Drug: APG-1252||Phase 1|
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 :||Interventional (Clinical Trial)|
|Estimated Enrollment :||50 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Masking Description:||Open label|
|Official Title:||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|
|Actual Study Start Date :||February 12, 2017|
|Estimated Primary Completion Date :||June 12, 2019|
|Estimated Study Completion Date :||September 12, 2019|
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.
Multiple dose cohorts, 30 minute IV infusion, twice weekly for 3 weeks of a cycle with 28 days.
Other Name: APG-1252 for injection
- Dose limit toxicity (DLT) determination [ Time Frame: 18 - 24 months ]Number of participants with APG-1252 treatment-related adverse events as assessed by CTCAE v4.0
- Maximum tolerated dose (MTD) determination [ Time Frame: 18 - 24 months ]If ≥ 2/6 patients develop a DLT at any dose level, then this dose will be declared as the MTD
- Pharmacokinetic evaluation [ Time Frame: 18 - 24 months ]Peak plasma concentration (Cmax) will be assessed on all participants with APG-1252 treatments
- Pharmacokinetic evaluation [ Time Frame: 18 - 24 months ]Area under the plasma concentration versus time curve (AUC) will be assessed on all participants with APG-1252 treatments
- Pharmacodynamic evaluation [ Time Frame: 18-24 months ]Platelet counts will be measured on the participants with APG-1252 treatments
- Pharmacodynamic evaluation [ Time Frame: 18-24 months ]Bcl-2 protein in PBMCs will be measured on the participants with APG-1252 treatments
- Pharmacodynamic evaluation [ Time Frame: 18-24 months ]Activation of apoptosis will be measured on the participants with APG-1252 treatments
- Preliminary efficacy assessment [ Time Frame: 18-24 months ]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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03080311
|Contact: Isabel Jimenez, RN, MSNemail@example.com|
|United States, Michigan|
|Grand Rapids, Michigan, United States, 49503|
|Contact: Kathy Estkowski, BS, CCRP 616-954-5554 firstname.lastname@example.org|
|Contact: Timothy J Cole, RN, BSN, OCN 616-954-5554 email@example.com|
|Principal Investigator: Nehal Lakhani, M.D., Ph.D.|
|United States, Texas|
|The START Center for Cancer Care||Recruiting|
|San Antonio, Texas, United States, 78229|
|Contact: Isabel Jimenez, RN, MSN 210-593-5265 firstname.lastname@example.org|
|Principal Investigator: Drew Resco, M.D.|
|Study Director:||Yifan Zhai, M.D., Ph.D.||Ascentage Pharma Group Inc.|