Small Cell Lung CancerPhase 1/2NCT04210037
Study of APG-1252 Plus Paclitaxel in Patients With Relapsed/Refractory Small Cell Lung Cancer
A Phase 1/2 study testing APG-1252 and Paclitaxel in people with Small Cell Lung Cancer, run by Ascentage Pharma Group Inc. at 8 sites in 2 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Small Cell Lung Cancer
- What is being tested?
- APG-1252 and Paclitaxel
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 8 sitesin 2 countries
- Study dates
- 20 Aug 2020to 15 May 2022
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
- Platelet count ≥ 100,000/mm˄3 Note: Use of transfusions or thrombopoietic agents to achieve baseline platelet count criterion is prohibited.
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- Hemoglobin ≥ 9.0 g/dL
- 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:
- Serum creatinine ≤ 1.5 × upper limit of normal (ULN); if serum creatinine is > 1.5 × ULN, creatinine clearance must be ≥ 50 mL/min
- Total bilirubin ≤ 1.5 × ULN; If patient has Gilbert's syndrome, may have bilirubin > 1.5 × ULN
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × ULN; for patients with known liver metastases, AST and ALT may be ≤ 5 × ULN
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
8 sites in 2 countries.
8 sites in 2 countries
United States6 sites
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, 48109
Winship Cancer Institute, Emory University
Atlanta, Georgia, 30322
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
Northwestern University
Chicago, Illinois, 60611
Virginia Cancer Specialists
Fairfax, Virginia, 22031
BRCR Medical Center
Plantation, Florida, 33322
Australia2 sites
Flinders Medical Centre
Bedford Park, South Australia, 5042
Westmead Hospital
Westmead, New South Wales, 2148
About this study
Official 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
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.
Read the detailed description
Upon enrollment, patients will undergo a comprehensive history and physical exam, along with baseline laboratory assessment. Baseline CT imaging will be required within 4 weeks prior to study entry. Archival tissue is mandatory; a fresh biopsy of the primary tumor or a metastatic lesion prior to initiation of therapy is optional and post-treatment tumor biopsy is strongly encouraged.
In the phase Ib portion, eligible patients will receive APG-1252 at the assigned dose-level on days 1, 8 and 15 plus a fixed-dose of paclitaxel 80 mg/m˄2 on days 1 and 8 of a 21-day cycle. There will be three dose-levels of APG-1252 (-1, 80 mg; 1, 160 mg; 2, 240 mg) with the first patient starting at dose-level 1 and subsequent patients at dose-levels determined by the TITE-CRM methodology. There will be no intra-patient dose-escalation. Patients will be continuously assessed for adverse events, including DLTs which are defined in the protocol. Response assessment by CT imaging will occur every 2 cycles and treatment will continue until progression of disease, unacceptable toxicity, patient preference to stop treatment, withdrawal of consent, or administrative discontinuation.
In the phase II portion, eligible patients will receive APG-1252 at the RP2D determined in the phase Ib portion on days 1, 8 and 15 plus paclitaxel 80 mg/m˄2 on days 1 and 8 of a 21-day cycle. Response assessment by CT imaging will occur every 2 cycles and treatment will continue until progression of disease, unacceptable toxicity, patient preference to stop treatment, withdrawal of consent, or administrative discontinuation.
- Conditions
- Small Cell Lung Cancer
- Being tested
- APG-1252, Paclitaxel
- Medical subject headings
- Small Cell Lung Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
APG-1252Drug
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.
PaclitaxelDrug
Also called Abraxane
80 mg/m˄2 on days 1 and 8 of a 21-day cycle
| Study group | Role | What they receive |
|---|---|---|
| APG-1252 160 mg | Experimental | intravenous infusion over 30 minutes on days 1, 8 and 15 Receives: Drug: APG-1252; Drug: Paclitaxel |
| APG-1252 240 mg | Experimental | intravenous infusion over 30 minutes on days 1, 8 and 15 Receives: Drug: APG-1252; Drug: Paclitaxel |
| APG-1252 80 mg | Experimental | intravenous infusion over 30 minutes on days 1, 8 and 15 Receives: Drug: APG-1252; Drug: Paclitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary Toxicity Endpoint: dose-limiting toxicity (DLT)
DLT will be will be assessed via CTCAE version 5.0
Measured: 21 days
Preliminary efficacy assessment
Partial or complete response according to RECIST v1.1 criteria measured at anytime with 12 months of start of therapy
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Dec 2019
- Study start20 Aug 2020
- Primary completion30 Aug 2021
- Study completion15 May 2022
Why it stopped: Sponsor decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by Ascentage Pharma Group Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- APG-1252 at the selected dose-level on days 1, 8 and 15 plus a fixed-dose of paclitaxel 80 mg/m˄2 on days 1 and 8 of a 21-day cycle. There will be three dose-levels of APG-1252 (-1, 80 mg; 1, 160 mg; 2, 240 mg).
- Masking
- None (open label)
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ascentage Pharma Group Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Yifan Zhai, MD, PhD, Study chair, Ascentage Pharma Group Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04210037
- Sponsor's protocol ID
- APG1252SU101
- Status last verified
- Jul 2022
- First submitted
- 20 Dec 2019
- Last updated
- 12 Jul 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT04210037
- Acronym / sponsor ID
- APG1252SU101
- Conditions
- Small Cell Lung Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor decision
- Enrolment
- 28 participants (actual)
- Lead sponsor
- Ascentage Pharma Group Inc.Industry (pharma, biotech, devices)
- Study start
- 20 Aug 2020 (actual)
- Primary completion
- 30 Aug 2021 (actual)
- Study completion
- 15 May 2022 (actual)
- First posted
- 24 Dec 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Upon enrollment, patients will undergo a comprehensive history and physical exam, along with baseline laboratory assessment. Baseline CT imaging will be required within 4 weeks prior to study entry. Archival tissue is mandatory; a fresh biopsy of the primary tumor or a metastatic lesion prior to initiation of therapy is optional and post-treatment tumor biopsy is strongly encouraged.
In the phase Ib portion, eligible patients will receive APG-1252 at the assigned dose-level on days 1, 8 and 15 plus a fixed-dose of paclitaxel 80 mg/m˄2 on days 1 and 8 of a 21-day cycle. There will be three dose-levels of APG-1252 (-1, 80 mg; 1, 160 mg; 2, 240 mg) with the first patient starting at dose-level 1 and subsequent patients at dose-levels determined by the TITE-CRM methodology. There will be no intra-patient dose-escalation. Patients will be continuously assessed for adverse events, including DLTs which are defined in the protocol. Response assessment by CT imaging will occur every 2 cycles and treatment will continue until progression of disease, unacceptable toxicity, patient preference to stop treatment, withdrawal of consent, or administrative discontinuation.
In the phase II portion, eligible patients will receive APG-1252 at the RP2D determined in the phase Ib portion on days 1, 8 and 15 plus paclitaxel 80 mg/m˄2 on days 1 and 8 of a 21-day cycle. Response assessment by CT imaging will occur every 2 cycles and treatment will continue until progression of disease, unacceptable toxicity, patient preference to stop treatment, withdrawal of consent, or administrative discontinuation.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- APG-1252 at the selected dose-level on days 1, 8 and 15 plus a fixed-dose of paclitaxel 80 mg/m˄2 on days 1 and 8 of a 21-day cycle. There will be three dose-levels of APG-1252 (-1, 80 mg; 1, 160 mg; 2, 240 mg).
| Arm | Type | Receives |
|---|---|---|
| APG-1252 160 mg | Experimental | Drug: APG-1252, Drug: Paclitaxelintravenous infusion over 30 minutes on days 1, 8 and 15 |
| APG-1252 240 mg | Experimental | Drug: APG-1252, Drug: Paclitaxelintravenous infusion over 30 minutes on days 1, 8 and 15 |
| APG-1252 80 mg | Experimental | Drug: APG-1252, Drug: Paclitaxelintravenous infusion over 30 minutes on days 1, 8 and 15 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- 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:
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| APG-1252APG-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. | Drug | APG-1252 160 mg, APG-1252 240 mg, APG-1252 80 mg |
| PaclitaxelAlso: Abraxane80 mg/m˄2 on days 1 and 8 of a 21-day cycle | Drug | APG-1252 160 mg, APG-1252 240 mg, APG-1252 80 mg |
Primary outcome
Primary Toxicity Endpoint: dose-limiting toxicity (DLT)
Time frame: 21 days
DLT will be will be assessed via CTCAE version 5.0
Preliminary efficacy assessment
Time frame: 12 months
Partial or complete response according to RECIST v1.1 criteria measured at anytime with 12 months of start of therapy
Results and safety
The study was stopped early (reason given: Sponsor decision). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jul 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yifan Zhai, MD, PhD study chair
Ascentage Pharma Group Inc.
8 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing APG-1252 and Paclitaxel in people with Small Cell Lung Cancer, run by Ascentage Pharma Group Inc. at 8 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 12 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States, Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Sponsor decision). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Primary Toxicity Endpoint: dose-limiting toxicity (DLT) (time frame: 21 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jul 2022.