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Small Cell Lung CancerPhase 1NCT03080311

A Study of APG-1252 in Patients With SCLC or Other Solid Tumors

A Phase 1 study testing APG-1252 in people with Small Cell Lung Cancer and Solid Tumor, run by Ascentage Pharma Group Inc. at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Small Cell Lung Cancer, Solid Tumor
What is being tested?
APG-1252
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
2 sitesUnited States
Study dates
12 Feb 2017to 17 Jul 2020
Phase
Phase 1
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 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
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  • 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

Who cannot join

  • 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)
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  • 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

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • START Midwest

    Grand Rapids, Michigan, 49503

  • The START Center for Cancer Care

    San Antonio, Texas, 78229

Other trials in United States

About this study

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

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.

Read the 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.

Being tested
APG-1252
Keywords
Bcl-2/Bcl-xL dual inhibitor
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

    Also called APG-1252 for injection

    Multiple dose cohorts, 30 minute IV infusion, twice weekly for 3 weeks of a cycle with 28 days.

Study groups in NCT03080311
Study groupRoleWhat they receive
APG-1252ExperimentalAn 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.
Receives: Drug: APG-1252

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose limiting toxicity (DLT) determination

    Number of participants with APG-1252 treatment-related adverse events as assessed by NCI CTCAE v4.03

    Measured: 28 days

  2. Maximum tolerated dose (MTD) determination

    If ≥ 2/6 patients develop a DLT at any dose level, then this dose will be declared as the MTD

    Measured: 18 - 24 months

Secondary outcomes (6)

  1. Pharmacokinetic evaluation

    Peak plasma concentration (Cmax) will be assessed on all participants with APG-1252 treatments

    Measured: 18 - 24 months

  2. Pharmacokinetic evaluation

    Area under the plasma concentration versus time curve (AUC) will be assessed on all participants with APG-1252 treatments

    Measured: 18 - 24 months

  3. Pharmacodynamic evaluation

    Platelet counts will be measured on the participants with APG-1252 treatments

    Measured: 18-24 months

  4. Pharmacodynamic evaluation

    Bcl-2 protein in peripheral blood mononuclear cells (PBMCs) will be measured on the participants with APG-1252 treatments

    Measured: 18-24 months

  5. Pharmacodynamic evaluation

    Activation of apoptosis will be measured on the participants with APG-1252 treatments

    Measured: 18-24 months

  6. Preliminary efficacy assessment

    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

    Measured: 18-24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Mar 2017
  2. Study start12 Feb 2017
  3. Primary completion22 Jun 2020
  4. Study completion17 Jul 2020

Resources

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
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
50 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03080311
Sponsor's protocol ID
APG-1252-US-001
Status last verified
Jul 2022
First submitted
12 Feb 2017
Last updated
12 Jul 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing APG-1252 in people with Small Cell Lung Cancer and Solid Tumor, run by Ascentage Pharma Group Inc. at 2 sites in United States.

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 19 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: finished, 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 2 sites in United States. 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 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.

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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Dose limiting toxicity (DLT) determination (time frame: 28 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?

On the ClinicalTrials.gov record for NCT03080311.

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.

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