Clinical Trials /

Study of Combination APG-1252 Plus Paclitaxel in Patients With Relapsed/Refractory Small Cell Lung Cancer

NCT04210037

Description:

A Multi-Center, Phase Ib/II Study of Combination APG-1252 plus Paclitaxel in Patients with Relapsed/Refractory Small Cell Lung Cancer (SCLC)

Related Conditions:
  • Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of Combination APG-1252 Plus Paclitaxel in Patients With Relapsed/Refractory Small Cell Lung Cancer
  • Official Title: A Multi-Center, Phase I/II Study of Combination APG-1252 Plus Paclitaxel in Patients With Relapsed/Refractory Small Cell Lung Cancer

Clinical Trial IDs

  • ORG STUDY ID: APG1252SU101
  • NCT ID: NCT04210037

Conditions

  • Small Cell Lung Cancer

Interventions

DrugSynonymsArms
APG1252Dose level -1
PaclitaxelAbraxaneDose level -1

Purpose

A Multi-Center, Phase Ib/II Study of Combination APG-1252 plus Paclitaxel in Patients with Relapsed/Refractory Small Cell Lung Cancer

Detailed Description

      This is a multi-center, open-label, phase Ib/II study of combination therapy with APG-1252
      plus paclitaxel in patients with relapsed/refractory SCLC. The phase Ib portion will be done
      using TITE-CRM methodology to determine the MTD 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.

      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/m2 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/m2 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.
    

Trial Arms

NameTypeDescriptionInterventions
Dose level 1ExperimentalAPG1252 160 mg intravenous infusion over 30 minutes on days 1, 8 and 15
  • APG1252
  • Paclitaxel
Dose level 2ExperimentalAPG1252 240 mg intravenous infusion over 30 minutes on days 1, 8 and 15
  • APG1252
  • Paclitaxel
Dose level -1ExperimentalAPG1252 80 mg intravenous infusion over 30 minutes on days 1, 8 and 15
  • APG1252
  • Paclitaxel

Eligibility Criteria

        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 0-2

          -  Adequate hematologic function as indicated by:

               1. Platelet count ≥ 100,000/mm3 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: aPTT and 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 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; see section 7.4 for contraceptive methods (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

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Primary Toxicity Endpoint: dose-limiting toxicity (DLT)
Time Frame:21 days
Safety Issue:
Description:DLT will be will be assessed via CTCAE version 5.0

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Ascentage Pharma Group Inc.

Last Updated

April 20, 2020