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出境医 / 临床实验 / A Phase I Study of AZD4635 in Japanese Patients With Advanced Solid Malignancies

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

Study Description
Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Advanced Solid Malignancies Drug: AZD4635 Phase 1

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.

Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
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.
Actual Study Start Date : July 4, 2019
Actual Primary Completion Date : September 7, 2020
Actual Study Completion Date : September 7, 2020
Arms and Interventions
Arm Intervention/treatment
Experimental: AZD4635 monotherapy
Dose escalation of AZD4635 monotherapy for patients with advanced solid malignancies
 Drug: AZD4635
AZD4635 taken orally
Outcome Measures
Primary Outcome Measures :
  1. The incidence of Adverse event and SAE [ Time Frame: From the informed consent to 30 days post last dose ]
    Investigate the safety and tolerability of AZD4635

  2. The incidence of Dose-limiting toxicity (DLTs) [ Time Frame: 25 days (Cycle0 and Cycle1) ]
    Investigate the safety and tolerability of AZD4635


Secondary Outcome Measures :
  1. 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. ]
    Summarize based on RECIST 1.1 by cohort and overall.

  2. 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. ]
    Characterize the single-dose and multiple-dose plasma of AZD4635

  3. 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. ]
    Summarize based on RECIST 1.1 by cohort and overall.

  4. 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. ]
    Characterize the single-dose and multiple-dose plasma of AZD4635


Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   20 Years to 130 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations

Locations
Layout table for location information
Japan
Research Site
Chuo-ku, Japan, 104-0045
Research Site
Kashiwa, Japan, 277-8577
Sponsors and Collaborators
AstraZeneca
Tracking Information
First Submitted Date  ICMJE May 24, 2019
First Posted Date  ICMJE June 10, 2019
Last Update Posted Date December 8, 2020
Actual Study Start Date  ICMJE July 4, 2019
Actual Primary Completion Date September 7, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 7, 2019)
  • The incidence of Adverse event and SAE [ Time Frame: From the informed consent to 30 days post last dose ]
    Investigate the safety and tolerability of AZD4635
  • The incidence of Dose-limiting toxicity (DLTs) [ Time Frame: 25 days (Cycle0 and Cycle1) ]
    Investigate the safety and tolerability of AZD4635
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 7, 2019)
  • 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. ]
    Summarize based on RECIST 1.1 by cohort and overall.
  • 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. ]
    Characterize the single-dose and multiple-dose plasma of AZD4635
  • 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. ]
    Summarize based on RECIST 1.1 by cohort and overall.
  • 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. ]
    Characterize the single-dose and multiple-dose plasma of AZD4635
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase I Study of AZD4635 in Japanese Patients With Advanced Solid Malignancies
Official Title  ICMJE 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.
Brief Summary 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Condition  ICMJE Advanced Solid Malignancies
Intervention  ICMJE Drug: AZD4635
AZD4635 taken orally
Study Arms  ICMJE Experimental: AZD4635 monotherapy
Dose escalation of AZD4635 monotherapy for patients with advanced solid malignancies
Intervention: Drug: AZD4635
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 31, 2020) 		10
Original Estimated Enrollment  ICMJE
 (submitted: June 7, 2019) 		12
Actual Study Completion Date  ICMJE September 7, 2020
Actual Primary Completion Date September 7, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 20 Years to 130 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Japan
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03980821
Other Study ID Numbers  ICMJE D8730C00005
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description:

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal.

All request will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home
Responsible Party AstraZeneca
Study Sponsor  ICMJE AstraZeneca
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account AstraZeneca
Verification Date December 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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