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A Phase I Study of AZD4635 in Japanese Patients With Advanced Solid Malignancies

NCT03980821

Description:

This is a Phase I, open-label study to assess the safety, tolerability, pharmacokinetics and anti-tumor activity of AZD4635 in Japanese patients with advanced solid malignancies. This study consists of 2 cohorts, Cohort1 and Cohort2. At least 3 or up to 6 evaluable Japanese patients with advanced solid malignancies will be enrolled in Cohort1 and 6 evaluable patients will be enrolled in Cohort2.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Phase I Study of AZD4635 in Japanese Patients With Advanced Solid Malignancies
  • Official Title: A Phase I, Open-label Study to Assess the Safety, Tolerability, Pharmacokinetics and Anti-tumor Activity of AZD4635 in Japanese Patients With Advanced Solid Malignancies

Clinical Trial IDs

  • ORG STUDY ID: D8730C00005
  • NCT ID: NCT03980821

Conditions

  • Advanced Solid Malignancies

Interventions

DrugSynonymsArms
AZD4635AZD4635 monotherapy

Purpose

This is a Phase I, open-label study to assess the safety, tolerability, pharmacokinetics and anti-tumor activity of AZD4635 in Japanese patients with advanced solid malignancies. This study consists of 2 cohorts, Cohort1 and Cohort2. At least 3 or up to 6 evaluable Japanese patients with advanced solid malignancies will be enrolled in Cohort1 and 6 evaluable patients will be enrolled in Cohort2.

Detailed Description

      Objectives:

      Primary objective:

      Investigate the safety and tolerability of AZD4635 monotherapy in Japanese patients

      Secondary objective:

      Characterize the single-dose and multiple-dose plasma pharmacokinetic (PK) parameters of
      AZD4635 monotherapy Determine the preliminary anti-tumor activity of AZD4645 monotherapy

      Overall design:

      This is a phase I, open-label study of AZD4635 in Japanese patients with advanced solid
      malignancies.

      The study consists of 2 cohorts, Cohort 1 and Cohort 2. At least 3 or up to 6 evaluable
      Japanese subjects with advanced solid malignancies will be enrolled in Cohort 1 and 6
      evaluable patients will be required for Cohort 2 to confirm the tolerability. The total
      number of evaluable subjects in each cohort will depend upon available data in each cohort
      and decision of Safety Review Committee(SRC).

      Study Period:

      The study is expected to start in June 2019 and end in June 2020.

      Number of Subjects:

      9 to 12 evaluable subjects will be enrolled in this study to confirm the tolerability.

      Treatments and treatment duration:

      Subjects will receive AZD4635 once daily (QD). A single dose of AZD4635 will be taken on
      Cycle 0 Day1 and the subsequent dose of AZD4635 will be taken from Cycle 1 Day 1 until
      discontinuation criterion is met. A cycle of study treatment will be defined as 21 days of
      continuous dosing.
    

Trial Arms

NameTypeDescriptionInterventions
AZD4635 monotherapyExperimentalDose escalation of AZD4635 monotherapy for patients with advanced solid malignancies
  • AZD4635

Eligibility Criteria

        Major Inclusion Criteria:

          -  Adult subjects; age ≥ 20 years

          -  Histologically or cytological confirmation of a solid, malignant tumor, excluding
             central nervous system (CNS) tumors and lymphoma, that is refractory to standard
             therapy or for which no standard of care regimen currently exists

          -  Patients must have either at least one lesion that can be evaluable using RECIST v1.1
             or patients with mCRPC must have measurable prostate specific antigen above normal
             limits (per local ranges)

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

          -  Normotensive or well controlled blood pressure, with or without current
             antihypertensive treatment

          -  Females of child-bearing potential must use 2 highly effective methods of
             contraception

          -  Male patients should be willing to use barrier contraception

        Major Exclusion Criteria:

          -  Any investigational medicinal product or other systemic anticancer treatment within at
             least 4 weeks prior to the first dose of study treatment, or within 8 weeks after
             immunotherapy or other long half-life antibody therapy, whichever is the most
             appropriate and as judged by the Investigator.

          -  Evidence of recent or significant cardiovascular disease

          -  Unresolved toxicities from prior therapy greater than CTCAE Grade 1 at starting study
             treatment

          -  History of seizures, CNS tumors or CNS metastasis

          -  Active or prior documented autoimmune or inflammatory disorders within the past 3
             years to the start of treatment

          -  Patients with prior ≥ Grade3 immune-mediated reactions

          -  Evidence of severe or uncontrolled systemic diseases

          -  Inadequate bone marrow reserve or organ function

          -  Refractory nausea and vomiting, chronic gastrointestinal diseases, or previous
             significant bowel resection that would preclude adequate absorption of AZD4635

          -  History of hypersensitivity to AZD4635 or drugs with a similar chemical structure or
             class to AZD4635

          -  Judgment by the Investigator that the patient should not participate in the study
      
Maximum Eligible Age:N/A
Minimum Eligible Age:20 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:The incidence of Adverse event and SAE
Time Frame:From the informed consent to 30 days post last dose
Safety Issue:
Description:Investigate the safety and tolerability of AZD4635

Secondary Outcome Measures

Measure:Objective response rate (ORR)
Time Frame:Tumor assessment is Cycle 4 Day 1 and then on Day 1 of each even numbered cycle (+/-5 days) until disease progression. Expected to be for up to 6 months.
Safety Issue:
Description:Summarize based on RECIST 1.1 by cohort and overall.
Measure:Maximum plasma concentration (Cmax)
Time Frame:Samples will be collected at pre-specified time points in the single-dose and multiple-dose portion of the study beginning with Cycle 1 Day 1 until last dose. Expected to be for up to 6 months.
Safety Issue:
Description:Characterize the single-dose and multiple-dose plasma of AZD4635
Measure:Disease control rate (DCR)
Time Frame:Tumor assessment is Cycle 4 Day 1 and then on Day 1 of each even numbered cycle (+/-5 days) until disease progression. Expected to be for up to 6 months.
Safety Issue:
Description:Summarize based on RECIST 1.1 by cohort and overall.
Measure:Area under the plasma concentration-time curve (AUC)
Time Frame:Samples will be collected at pre-specified time points in the single-dose and multiple-dose portion of the study beginning with Cycle 1 Day 1 until last dose. Expected to be for up to 6 months.
Safety Issue:
Description:Characterize the single-dose and multiple-dose plasma of AZD4635

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:AstraZeneca

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