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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04210037




Registration number
NCT04210037
Ethics application status
Date submitted
20/12/2019
Date registered
24/12/2019
Date last updated
7/05/2021

Titles & IDs
Public title
Study of APG-1252 Plus Paclitaxel in Patients With Relapsed/Refractory Small Cell Lung Cancer
Scientific title
A Multi-Center, Phase Ib/II Study of Combination Treatment of APG-1252 With Paclitaxel in Patients With Relapsed/Refractory Small Cell Lung Cancer
Secondary ID [1] 0 0
APG1252SU101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Small Cell Lung Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - APG-1252
Treatment: Drugs - Paclitaxel

Experimental: APG-1252 160 mg - intravenous infusion over 30 minutes on days 1, 8 and 15

Experimental: APG-1252 240 mg - intravenous infusion over 30 minutes on days 1, 8 and 15

Experimental: APG-1252 80 mg - intravenous infusion over 30 minutes on days 1, 8 and 15


Treatment: Drugs: APG-1252
APG-1252 (Ascentage Pharma) is a highly potent Bcl-2 family protein inhibitor with high binding affinity for Bcl-2, Bcl-xL and Bcl-w. APG-1252 possesses strong antitumor activity as a single-agent against tumor cells addicted to Bcl-2/Bcl-xL, and exhibits a much broader antitumor activity when combined with chemotherapeutic agents.

Treatment: Drugs: Paclitaxel
80 mg/m^2 on days 1 and 8 of a 21-day cycle

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Primary Toxicity Endpoint: dose-limiting toxicity (DLT) - DLT will be will be assessed via CTCAE version 5.0
Timepoint [1] 0 0
21 days
Primary outcome [2] 0 0
Preliminary efficacy assessment - Partial or complete response according to RECIST v1.1 criteria measured at anytime with 12 months of start of therapy
Timepoint [2] 0 0
12 months

Eligibility
Key inclusion criteria
- Histologically or cytologically confirmed SCLC

- Progression of disease on or after initial treatment with platinum-based therapy with
or without thoracic radiotherapy; patients may have also received prior immunotherapy
or other chemotherapy agents, except for paclitaxel; there is no limit on the number
of prior treatment regimens allowed

- Male or non-pregnant, non-lactating female patients

- Eastern Cooperative Oncology Group (ECOG) performance status 0-1

- Adequate hematologic function as indicated by:

1. Platelet count = 100,000/mm^3 Note: Use of transfusions or thrombopoietic agents
to achieve baseline platelet count criterion is prohibited.

2. Hemoglobin = 9.0 g/dL

3. Absolute neutrophil count (ANC) = 1000/µL Note: Use of growth-factors to maintain
ANC criterion prior to enrollment is not permitted.

- Adequate renal and liver function as indicated by:

1. Serum creatinine = 1.5 × upper limit of normal (ULN); if serum creatinine is >
1.5 × ULN, creatinine clearance must be = 50 mL/min

2. Total bilirubin = 1.5 × ULN; If patient has Gilbert's syndrome, may have
bilirubin > 1.5 × ULN

3. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 3 × ULN;
for patients with known liver metastases, AST and ALT may be = 5 × ULN

4. Coagulation: activated partial thromboplastin time (aPTT) and prothrombin time
(PT) = 1.2 × ULN

- Patients with previously treated, clinically controlled brain metastases are allowed.
Clinically controlled is defined as surgical excision and/or radiation therapy
followed by at least 14 days of stable neurologic function and no evidence of central
nervous system (CNS) disease progression as determined by CT or MRI within 14 days
prior to study enrollment. Continued use of corticosteroids is permissible.

- Willingness to use contraception by a method that is deemed effective by the
investigator by both males and female patients of child bearing potential and their
partners throughout the treatment period and for at least three months following the
last dose of study drug (postmenopausal women must have been amenorrheic for at least
12 months to be considered of non-childbearing potential).

- Able to understand and willing to sign a written informed consent form

- Able and willing to comply with study procedures and follow-up examination
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Receiving concurrent anti-cancer therapy (chemotherapy, radiation therapy, surgery,
immunotherapy, hormonal therapy, targeted therapy, biologic therapy) or any
investigational therapy within 14 days prior to the first dose of treatment, with the
exception of hormones for hypothyroidism, estrogen replacement therapy (ERT),
anti-estrogen analogs, or agonists required to suppress serum testosterone levels

- Continuance of toxicities due to prior treatment that do not recover to < grade 2,
except for clinically insignificant toxicities such as lymphopenia or alopecia

- Known bleeding diathesis/disorder

- Recent history of non-chemotherapy induced thrombocytopenia associated a major
bleeding episode within 1 year prior to study entry

- 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 of study entry

- Use of therapeutic doses of anti-coagulants is an exclusion, including anti-platelet
agents. Use of low-dose anticoagulation medications to maintain the patency of a
central intravenous catheter or aspirin (<100 mg) for cardiovascular protection are
permitted.

- Failure to recover adequately from prior surgical procedures, as judged by the
investigator. 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 are excluded. (Minor
surgery is invasive operative procedure involving resecting skin or mucus membranes
and connective tissue. Major surgery is an invasive operative procedure involving more
extensive resection, such as body cavity opening or organ resection.)

- Unstable angina, myocardial infarction, or a coronary revascularization procedure
within 180 days of study entry

- 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

- Uncontrolled concurrent illness that would limit compliance with the study
requirements, including, but not limited to: serious uncontrolled infection,
symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or
psychiatric illness

- Prior treatment with a Bcl-2/Bcl-xL inhibitor

- Prior treatment with paclitaxel

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1/Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA
Recruitment hospital [1] 0 0
Westmead Hospital - Westmead
Recruitment hospital [2] 0 0
Flinders Medical Centre - Bedford Park
Recruitment postcode(s) [1] 0 0
2148 - Westmead
Recruitment postcode(s) [2] 0 0
5042 - Bedford Park
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Florida
Country [2] 0 0
United States of America
State/province [2] 0 0
Georgia
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
Massachusetts
Country [5] 0 0
United States of America
State/province [5] 0 0
Michigan
Country [6] 0 0
United States of America
State/province [6] 0 0
Virginia

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Ascentage Pharma Group Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a multi-center, open-label, phase Ib/II study of combination therapy with APG-1252
plus paclitaxel in patients with relapsed/refractory small-cell lung cancer(SCLC). The phase
Ib portion will be done using time-to-event continual reassessment method (TITE-CRM)
methodology to determine the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) of
APG-1252 with a fixed dose of paclitaxel. The phase II portion will utilize a Simon two-stage
design to determine the efficacy of the combination therapy with response rate as the primary
endpoint.
Trial website
https://clinicaltrials.gov/show/NCT04210037
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Yifan Zhai, MD, PhD
Address 0 0
Ascentage Pharma Group Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Kathryn Shantz
Address 0 0
Country 0 0
Phone 0 0
301-802-3414
Fax 0 0
Email 0 0
kate.shantz@ascentage.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04210037