Trial Review

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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06130553




Registration number
NCT06130553
Ethics application status
Date submitted
19/10/2023
Date registered
14/11/2023
Date last updated
14/08/2024

Titles & IDs
Public title
A Study of AZD3470, a PRMT5 Inhibitor, in Patients With MTAP Deficient Advanced/Metastatic Solid Tumours
Scientific title
PRIMROSE: A Modular Phase I/IIa, Multi-centre, Dose Escalation, and Expansion Study of AZD3470, a MTA Cooperative PRMT5 Inhibitor, as Monotherapy and in Combination With Anticancer Agents in Patients With Advanced/Metastatic Solid Tumours That Are MTAP Deficient
Secondary ID [1] 0 0
165618
Secondary ID [2] 0 0
D9970C00001
Universal Trial Number (UTN)
Trial acronym
PRIMROSE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
BEHAVIORAL - Pulmonary Fibrosis self-management package and smartphone application
Treatment: Drugs - AZD3470

BEHAVIORAL: Pulmonary Fibrosis self-management package and smartphone application
The pulmonary fibrosis package includes modules on understanding treatment options for pulmonary fibrosis, managing medication and side effects, understanding and accessing clinical trials, managing shortness of breath, managing fatigue and mood, managing co-existing conditions, the role and importance of pulmonary rehabilitation and regular physical activity, role of oxygen therapy, smoking cessation advice and support, accessing community support, and communicating with others when living with pulmonary fibrosis.

The RE-BUILD app is used as a tool for data collection and to help participants self-monitor their disease over time. Participants enter their health data, including baseline conditions, medications and diagnosis, pulmonary function results and supplementary oxygen use. It also tracks air quality data close to the participant as well as physical activity level (step count). The app also has links to ILD-related educational resources.

Treatment: Drugs: AZD3470
AZD3470 is a novel, potent and selective, second-generation, methylthioadenosine (MTA)-selective, small molecule inhibitor of PRMT5.
Intervention code [1] 0 0
BEHAVIORAL
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of adverse events (AEs) and serious adverse events (SAEs)
Timepoint [1] 0 0
From time of informed consent to 28 days post last dose of AZD3470
Primary outcome [2] 0 0
Incidence of dose-limiting toxicities (DLT)
Timepoint [2] 0 0
From first dose of study treatment until the end of Cycle 1 (each cycle is 21 days)
Secondary outcome [1] 0 0
Radiological response assessed by the Investigator evaluated according to RECIST v1.1 - ORR (Objective Response Rate)
Timepoint [1] 0 0
From date of first dose of AZD3470 up until progression, or the last evaluable assessment in the absence of progression (approximately 2 years).
Secondary outcome [2] 0 0
Radiological response assessed by the Investigator evaluated according to RECIST v1.1 - DoR (Duration of Response)
Timepoint [2] 0 0
From date of first dose of AZD3470 up until progression, or the last evaluable assessment in the absence of progression (approximately 2 years).
Secondary outcome [3] 0 0
Radiological response assessed by the Investigator evaluated according to RECIST v1.1 - Best percentage change in tumour size
Timepoint [3] 0 0
From date of first dose of AZD3470 up until progression, or the last evaluable assessment in the absence of progression (approximately 2 years).
Secondary outcome [4] 0 0
Radiological response assessed by the Investigator evaluated according to RECIST v1.1 - PFS (Progression Free Survival)
Timepoint [4] 0 0
From date of first dose of AZD3470 up until progression, or the last evaluable assessment in the absence of progression (approximately 2 years).
Secondary outcome [5] 0 0
Radiological response assessed by the Investigator evaluated according to RECIST v1.1 - DCR (Disease Control Rate) at 12 weeks
Timepoint [5] 0 0
From date of first dose of AZD3470 up until progression, or the last evaluable assessment in the absence of progression (for each patient this is expected to be measured at 12 weeks).
Secondary outcome [6] 0 0
Overall Survival (OS)
Timepoint [6] 0 0
From date of first dose of AZD3470 up until the date of death due to any cause (approximately 2 years).
Secondary outcome [7] 0 0
Module 1 Endpoints Part A (Dose escalation) Measurement of PK parameters: AUC
Timepoint [7] 0 0
At predefined intervals throughout the treatment period (for each patient this is expected to be measured up to approximately 4 weeks)
Secondary outcome [8] 0 0
Module 1 Endpoints Part A (Dose escalation) Measurement of PK parameters: C-max
Timepoint [8] 0 0
At predefined intervals throughout the treatment period (for each patient this is expected to be measured up to approximately 4 weeks)
Secondary outcome [9] 0 0
Module 1 Endpoints Part A (Dose escalation) Measurement of PK parameters: half life
Timepoint [9] 0 0
At predefined intervals throughout the treatment period (for each patient this is expected to be measured up to approximately 4 weeks)
Secondary outcome [10] 0 0
Module 1 Endpoints Part A (Dose escalation) Measurement of PK parameters: Ae (excreted in urine)
Timepoint [10] 0 0
At predefined intervals throughout the treatment period (for each patient this is expected to be measured up to approximately 4 weeks)
Secondary outcome [11] 0 0
Module 1 Endpoints Part A (Dose escalation) Measurement of PK parameters: Clr (renal clearance)
Timepoint [11] 0 0
At predefined intervals throughout the treatment period (for each patient this is expected to be measured up to approximately 4 weeks)

Eligibility
Key inclusion criteria
Principal

* Participant must be at least 18 years of age or the legal age of consent in the jurisdiction in which the study is taking place, at the time of signing the ICF.
* Willing to provide archival and/or baseline tumour sample to meet the minimum tissue requirement for central MTAP deficiency testing.
* Participants must have received and progressed, are refractory or are intolerant to standard therapy for the specific tumour type. All participants are required to have had at least one prior line of treatment in the recurrent or metastatic setting.
* MTAP deficient tumours defined as evidence of homozygous deletion of one or more exons of the MTAP gene in tumour tissue AND/OR loss of MTAP expression in the tumour tissue.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
* A minimum life expectance of 12 weeks in the opinion of the Investigator.
* Participants must have at least one measurable lesion according to Response Evaluation Criteria in Solid Tumours (RECIST) v1.1
* Adequate organ and bone marrow reserve function.
* Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

Principal
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Spinal cord compression or symptomatic and unstable brain metastases or leptomeningeal disease.
* Allogenic organ transplantation.
* Any significant laboratory finding or any severe and uncontrolled medical condition.
* Any of the following cardiac criteria:
* LVEF = 50%
* prior or current cardiomyopathy
* clinically active cardiovascular disease, or a history of myocardial infarction within the last 6 months
* uncontrolled angina or acute coronary syndrome within 6 months
* severe valvular heart disease
* uncontrolled hypertension
* risk of brain perfusion problems. Stroke or transient ischemic attack in the last 6 months, undergone coronary artery bypass graft, angioplasty or vascular stent
* chronic heart failure
* factors that increase the risk of QTc prolongation or risk of arrhythmic events
* Mean resting QTcF > 470 msec or any clinically important abnormalities in rhythm
* Use of therapeutic anti-coagulation for treatment of active thromboembolic events.
* Serologic active hepatitis B or C infection.
* Known to have tested positive for Human immunodeficiency virus (HIV).
* Confirmed or suspected ILD/pneumonitis or history of (non-infectious) ILD/pneumonitis that required oral or IV steroids or supplemental oxygen
* Active gastrointestinal disease or other condition that would interfere with oral therapy.
* History of another primary malignancy.
* Unresolved toxicities from prior anti-cancer therapy, except alopecia and neuropathy.
* Prior treatment with a protein arginine methyltransferase 5 (PRMT5) inhibitor.

Study design
Purpose of the study
Treatment
Allocation to intervention
NA
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
18/01/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
26/02/2026
Actual
Sample size
Target
210
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AstraZeneca
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
AstraZeneca Clinical Study Information Center
Address 0 0
Country 0 0
Phone 0 0
1-877-240-9479
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT06130553