Advanced Solid MalignanciesPhase 1NCT03980821
A Phase I Study of AZD4635 in Japanese Patients With Advanced Solid Malignancies
A Phase 1 study testing AZD4635 in people with Advanced Solid Malignancies, run by AstraZeneca at 2 sites in Japan.
Trial 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. Read more about this study
- Who is it for?
- Ages 20 to 130 years
- Conditions the study is for
- Advanced Solid Malignancies
- What is being tested?
- AZD4635
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 2 sitesJapan
- Study dates
- 4 Jul 2019to 7 Sep 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 20 to 130 years
- All sexes
- No healthy volunteers
- Adult, Older adult
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
Trial locations and contacts
2 sites in 1 country.
About this study
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.
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.
Read the 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.
- Conditions
- Advanced Solid Malignancies
- Being tested
- AZD4635
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD4635Drug
AZD4635 taken orally
| Study group | Role | What they receive |
|---|---|---|
| AZD4635 monotherapy | Experimental | Dose escalation of AZD4635 monotherapy for patients with advanced solid malignancies Receives: Drug: AZD4635 |
What is being measured
The primary outcome is the main question the study is designed to answer.
The incidence of Adverse event and SAE
Investigate the safety and tolerability of AZD4635
Measured: From the informed consent to 30 days post last dose
The incidence of Dose-limiting toxicity (DLTs)
Investigate the safety and tolerability of AZD4635
Measured: 25 days (Cycle0 and Cycle1)
Secondary outcomes (4)
Objective response rate (ORR)
Summarize based on RECIST 1.1 by cohort and overall.
Measured: 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.
Maximum plasma concentration (Cmax)
Characterize the single-dose and multiple-dose plasma of AZD4635
Measured: 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.
Disease control rate (DCR)
Summarize based on RECIST 1.1 by cohort and overall.
Measured: 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.
Area under the plasma concentration-time curve (AUC)
Characterize the single-dose and multiple-dose plasma of AZD4635
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jun 2019
- Study start4 Jul 2019
- Primary completion7 Sep 2020
- Study completion7 Sep 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Advanced Solid MalignanciesStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe 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
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03980821
- Sponsor's protocol ID
- D8730C00005
- Status last verified
- Dec 2020
- First submitted
- 24 May 2019
- Last updated
- 8 Dec 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
Matsubara N, Kusuhara S, Yamamoto N, Sudo K, Yanagita M, Murayama K, Kawasumi H, Russell DL, Yin D, Shimizu T. Safety and pharmacokinetics of imaradenant (AZD4635) in Japanese patients with advanced solid malignancies: a phase I, open-label study. Cancer Chemother Pharmacol. 2024 Apr;93(4):341-352. doi: 10.1007/s00280-023-04605-9. Epub 2023 Dec 13.
PubMed 38086998
Study at a glance
From the registry record, last updated by the sponsor on 8 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT03980821
- Acronym / sponsor ID
- D8730C00005
- Conditions
- Advanced Solid Malignancies
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 4 Jul 2019 (actual)
- Primary completion
- 7 Sep 2020 (actual)
- Study completion
- 7 Sep 2020 (actual)
- First posted
- 10 Jun 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 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 design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| AZD4635 monotherapy | Experimental | Drug: AZD4635Dose escalation of AZD4635 monotherapy for patients with advanced solid malignancies |
Who may qualify
- Ages
- 20 to 130 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| AZD4635AZD4635 taken orally | Drug | AZD4635 monotherapy |
Primary outcome
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
4 secondary outcomes
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.
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.
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.
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Dec 2020.
- Derived from this study: PubMed 38086998Matsubara N, Kusuhara S, Yamamoto N, Sudo K, Yanagita M, Murayama K, Kawasumi H, Russell DL, Yin D, Shimizu T. Safety and pharmacokinetics of imaradenant (AZD4635) in Japanese patients with advanced solid malignancies: a phase I, open-label study. Cancer Chemother Pharmacol. 2024 Apr;93(4):341-352. doi: 10.1007/s00280-023-04605-9. Epub 2023 Dec 13.
- Individual participant dataSharing planned: Yes. 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.
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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.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AZD4635 in people with Advanced Solid Malignancies, run by AstraZeneca at 2 sites in Japan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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 8 Dec 2020. 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 Japan. 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?
The incidence of Adverse event and SAE (time frame: From the informed consent to 30 days post last dose). 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 NCT03980821, which also lists 1 linked publication.
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 8 Dec 2020.