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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04644068




Registration number
NCT04644068
Ethics application status
Date submitted
26/10/2020
Date registered
25/11/2020
Date last updated
25/06/2024

Titles & IDs
Public title
Study of AZD5305 as Monotherapy and in Combination With Anti-cancer Agents in Patients With Advanced Solid Malignancies
Scientific title
A Modular Phase I/IIa, Open-label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of Ascending Doses of AZD5305 as Monotherapy and in Combination With Anti-cancer Agents in Patients With Advanced Solid Malignancies
Secondary ID [1] 0 0
2020-002688-77
Secondary ID [2] 0 0
D9720C00001
Universal Trial Number (UTN)
Trial acronym
PETRA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ovarian Cancer 0 0
Breast Cancer 0 0
Pancreatic Cancer 0 0
Prostate Cancer 0 0
Additional Indications Below for Module 4 and 5 0 0
Non-small Cell Lung Cancer 0 0
Colorectal Cancer 0 0
Bladder Cancer 0 0
Gastric Cancer 0 0
Biliary Cancer 0 0
Cervical Cancer 0 0
Endometrial Cancer 0 0
Small Cell Lung Cancer Only in Module 5 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell
Cancer 0 0 0 0
Prostate
Cancer 0 0 0 0
Pancreatic
Cancer 0 0 0 0
Ovarian and primary peritoneal
Cancer 0 0 0 0
Womb (Uterine or endometrial cancer)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - AZD5305
Treatment: Drugs - Paclitaxel
Treatment: Drugs - Carboplatin
Treatment: Drugs - T- Dxd
Treatment: Drugs - Dato-DXd
Treatment: Drugs - Camizestrant

Experimental: Module 1: AZD5305 Monotherapy - AZD5305 Monotherapy

Experimental: Module 2: AZD5305 + Paclitaxel - AZD5305 + Paclitaxel

Experimental: Module 3: AZD5305 + Carboplatin with or without Paclitaxel - AZD5305 + Carboplatin with or without Paclitaxel

Experimental: Module 4: AZD5305 + Trastuzumab Deruxtecan - AZD5305 + T- DXd

Experimental: Module 5 AZD5305 + Datopotamab Deruxtecan - AZD5305 + Dato-DXd

Experimental: Module 6 AZD5305 + Camizestrant - AZD5305 + Camizestrant


Treatment: Drugs: AZD5305
Oral PARP inhibitor

Treatment: Drugs: Paclitaxel
IV Anti-microtubule agent

Treatment: Drugs: Carboplatin
IV Platinum chemotherapeutic

Treatment: Drugs: T- Dxd
IV Antibody-drug conjugate

Treatment: Drugs: Dato-DXd
IV Antibody-drug conjugate

Treatment: Drugs: Camizestrant
Oral SERD Molecule

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
The number of subjects with adverse events/serious adverse events
Timepoint [1] 0 0
From time of Informed Consent to 28 + 7 days post last dose ( modules 1,2,3,5 and 6). 40+7 days post last dose for Module 4.
Primary outcome [2] 0 0
The number of subjects with dose-limiting toxicity (DLT), as defined in the protocol.
Timepoint [2] 0 0
From first dose of study treatment until the end of Cycle 1.
Secondary outcome [1] 0 0
Best percentage change in target lesion
Timepoint [1] 0 0
From Screening to confirmed progressive disease (approximately 1 year)
Secondary outcome [2] 0 0
Objective Response Rate
Timepoint [2] 0 0
From Screening to confirmed progressive disease (approximately 1 year)
Secondary outcome [3] 0 0
Duration of Response
Timepoint [3] 0 0
From Screening to confirmed progressive disease (approximately 1 year)
Secondary outcome [4] 0 0
Progression Free Survival
Timepoint [4] 0 0
From Screening to confirmed progressive disease (approximately 1 year)
Secondary outcome [5] 0 0
Time To Response
Timepoint [5] 0 0
From Screening to confirmed progressive disease (approximately 1 year)
Secondary outcome [6] 0 0
Effects of AZD5305 on pH2AX (Ser139) PD biomarker
Timepoint [6] 0 0
From Cycle 0 Day 1 to Cycle 1 Day 15 (approximately 21 days)
Secondary outcome [7] 0 0
CA125 response (ovarian cancer)
Timepoint [7] 0 0
From Screening to confirmed progressive disease (approximately 1 year)
Secondary outcome [8] 0 0
Module 1: Area Under Curve (AUC)
Timepoint [8] 0 0
At predefined intervals throughout the treatment period (approximately 12 weeks)
Secondary outcome [9] 0 0
Module 1: Maximum plasma concentration of the drug (Cmax)
Timepoint [9] 0 0
At predefined intervals throughout the treatment period (approximately 12 weeks)
Secondary outcome [10] 0 0
Module 1: The time taken to reach the maximum concentration (Tmax)
Timepoint [10] 0 0
At predefined intervals throughout the treatment period (approximately 12 weeks)
Secondary outcome [11] 0 0
Module 1 and Module 5: Objective Response Rate (prostate cancer)
Timepoint [11] 0 0
From Screening to confirmed progressive disease (approximately 1 year)
Secondary outcome [12] 0 0
Module 1: Radiographic progression free survival (prostate cancer)
Timepoint [12] 0 0
From Screening to confirmed progressive disease (approximately 1 year)
Secondary outcome [13] 0 0
Module 1: Proportion of subjects with = 50% PSA decrease (prostate cancer)
Timepoint [13] 0 0
From Screening to confirmed progressive disease (approximately 1 year)
Secondary outcome [14] 0 0
Module 1 : To investigate the effect of a high-fat meal on the PK of AZD5305
Timepoint [14] 0 0
Cycle 0, Day 1 (C0D1), in either the "fasted" or "fed" state, followed by a single oral dose of AZD5305 in the other state for Cycle 1, Day 1 (C1D1) at least 72 hours later; 1 cycle is 28 days.
Secondary outcome [15] 0 0
Module 2: Area Under Curve (AUC)
Timepoint [15] 0 0
At predefined intervals throughout the treatment period (approximately 12 weeks)
Secondary outcome [16] 0 0
Module 2: Maximum plasma concentration of the drug (Cmax)
Timepoint [16] 0 0
At predefined intervals throughout the treatment period (approximately 12 weeks)
Secondary outcome [17] 0 0
Module 2: The time taken to reach the maximum concentration (Tmax)
Timepoint [17] 0 0
At predefined intervals throughout the treatment period (approximately 12 weeks)
Secondary outcome [18] 0 0
Module 3: Area Under Curve (AUC)
Timepoint [18] 0 0
At predefined intervals throughout the treatment period (approximately 12 weeks)
Secondary outcome [19] 0 0
Module 3: Maximum plasma concentration of the drug (Cmax)
Timepoint [19] 0 0
At predefined intervals throughout the treatment period (approximately 12 weeks)
Secondary outcome [20] 0 0
Module 3: The time taken to reach the maximum concentration (Tmax)
Timepoint [20] 0 0
At predefined intervals throughout the treatment period (approximately 12 weeks)
Secondary outcome [21] 0 0
Module 4 : Area Under Curve
Timepoint [21] 0 0
At predefined intervals throughout the treatment period (approximately 12 weeks)
Secondary outcome [22] 0 0
Module 4: Maximum plasma concentration of the drug (Cmax)
Timepoint [22] 0 0
At predefined intervals throughout the treatment period (approximately 12 weeks)
Secondary outcome [23] 0 0
Module 4: The time taken to reach the maximum concentration (Tmax)
Timepoint [23] 0 0
At predefined intervals throughout the treatment period (approximately 12 weeks)
Secondary outcome [24] 0 0
Module 4: Anti-Drug Antibody (ADA)
Timepoint [24] 0 0
Samples will be collected within 1 hour before dose administration on Day 1 of Cycle 1, 2, and 4, then every 4 Cycles (each cycle is 21 days), EoT, and at safety follow-up (40 days after last dose) as per Schedule of Assessments
Secondary outcome [25] 0 0
Module 4: To assess the preliminary anti-tumour activity of AZD5305 as monotherapy and in combination with T-DXd.
Timepoint [25] 0 0
From screening to approximately 6 months
Secondary outcome [26] 0 0
Module 5: Area Under Curve
Timepoint [26] 0 0
At predefined intervals throughout the treatment period (approximately 12 weeks)
Secondary outcome [27] 0 0
Module 5: Maximum plasma concentration of the drug (Cmax)
Timepoint [27] 0 0
At predefined intervals throughout the treatment period (approximately 12 weeks)
Secondary outcome [28] 0 0
Module 5: The time taken to reach the maximum concentration (Tmax)
Timepoint [28] 0 0
At predefined intervals throughout the treatment period (approximately 12 weeks)
Secondary outcome [29] 0 0
Module 5: Anti-Drug Antibody (ADA)
Timepoint [29] 0 0
Whole blood samples for determination of ADA for Dato-DXd in plasma will be collected in patients receiving Dato-DXd per the schedule specified in the SoA : Day 1 of Cycle 1, 2, 4, and 8 (each cycle is 21 days) , EoT, and then 28 day follow up visit.
Secondary outcome [30] 0 0
Module 5: Premilinary anti tumour activity AZD5305 in combination with
Timepoint [30] 0 0
From screening to confirmed progresive disease ( approximately 12 weeks)
Secondary outcome [31] 0 0
Module 6: To characterise the PK of AZD5305 and camizestrant following a single dose and at steady state after multiple dosing, when given in combination.
Timepoint [31] 0 0
At predefined interval throughout the treatment (approximately 12 weeks)
Secondary outcome [32] 0 0
Module 6: To evaluate the effect of camizestrant on the PK of AZD5305.
Timepoint [32] 0 0
At predefined intervals throughout the treatment period (approximately 12 weeks)
Secondary outcome [33] 0 0
Module 6: To evaluate the effect of AZD5305 on the PK of Camizestrant.
Timepoint [33] 0 0
At predefined intervals throughout the treatment period (approximately 12 weeks)

Eligibility
Key inclusion criteria
Key

* Age = 18 at the time of screening
* Histological or cytological confirmation of advanced malignancy considered to be suitable for study treatment and meeting module specific eligibility criteria..
* Eastern Cooperative Oncology Group Performance status (ECOG PS: 0-2)
* Life expectancy = 12 weeks
* Progressive cancer at the time of study entry
* Patients must have evaluable disease as defined in module-specific criteria for Part A and Part B
* Adequate organ and marrow function as defined by the protocol.
* For Part B expansion cohorts: Provision of formalin-fixed and paraffin embedded (FFPE) tumour specimen is mandatory, where available, except if stated that it is optional in a specific Module.

For Part A:

- Patients may have received up to one prior line of therapy with a PARPi-based regimen (either as a treatment or as maintenance)

For Part B:

- Patients must not have received prior therapy with a PARPi-based regimen (either as a treatment or as maintenance).

Key
Minimum age
18 Years
Maximum age
130 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Treatment with any of the following:

1. Nitrosourea or mitomycin C within 6 weeks of the first dose of study treatment
2. Any investigational agents or study drugs from a previous clinical study within 5 half-lives or 3 weeks (whichever is shorter) of the first dose of study treatment
3. Any other chemotherapy, immunotherapy or anticancer agents within 3 weeks of the first dose of study treatment
4. Any live virus or bacterial vaccine within 28 days of the first dose of study treatment
* Concomitant use of medications or herbal supplements known to be cytochrome P450 3A4 (CYP3A4) strong and moderate inhibitors or inducers.
* Concomitant use of drugs that are known to prolong or shorten QT and have a known risk of Torsades de Pointes.
* Receiving continuous corticosteroids at a dose of >10 mg prednisone/day or equivalent for any reason.
* Major surgery within 4 weeks of the first dose of study treatment.
* Radiotherapy with a wide field of radiation within 4 weeks or radiotherapy with a limited field of radiation for palliation within 2 weeks of the first dose of study treatment.
* Any history of persisting (> 2 weeks) severe pancytopenia due to any cause
* Spinal cord compression or brain metastases unless asymptomatic, treated and stable and not requiring continuous corticosteroids at a dose of >10mg prednisone/day or equivalent for at least 4 weeks prior to start of study treatment. Patients with leptomeningeal carcinomatosis are excluded.
* patient with known predisposition to bleeding (e.g., active peptic ulceration, recent [within 6 months] haemorrhagic stroke, proliferative diabetic retinopathy).
* Cardiac conditions as defined by the clinical study protocol
* Other cardiovascular diseases as defined by any of the following:

1. Symptomatic heart failure,
2. uncontrolled hypertension,
3. hypertensive heart disease with significant left ventricular hypertrophy
4. acute coronary syndrome (ACS)/acute myocardial infarction (AMI), unstable angina pectoris, coronary intervention procedure with percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) within 6 months.
5. cardiomyopathy of any etiology
6. presence of clinically significant valvular heart disease
7. history of atrial or ventricular arrhythmia requiring treatment; subjects with atrial fibrillation and optimally controlled ventricular rate (< 100 beats per minute) are permitted.
8. subjects with atrial fibrillation and optimally controlled ventricular rate are permitted
9. transient ischaemic attack, or stroke within 6 months prior to screening
10. patients with symptomatic hypotension at screening
* Patients with myelodysplastic syndrome/acute myeloid leukaemia or with features suggestive of myelodysplastic syndrome (MDS)/acute myeloid leukaemia (AML).
* Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of AZD5305
* Known allergy or hypersensitivity to investigational product(s) or any of the excipients of the investigational product(s).

Prior malignancy whose natural history, in the Investigator's opinion, has the potential to interfere with safety and efficacy assessments of the investigational regimen.

other module-specific criteria may apply

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Heidelberg
Recruitment hospital [2] 0 0
Research Site - Melbourne
Recruitment postcode(s) [1] 0 0
3084 - Heidelberg
Recruitment postcode(s) [2] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Massachusetts
Country [3] 0 0
United States of America
State/province [3] 0 0
New York
Country [4] 0 0
United States of America
State/province [4] 0 0
Oklahoma
Country [5] 0 0
United States of America
State/province [5] 0 0
Texas
Country [6] 0 0
Canada
State/province [6] 0 0
British Columbia
Country [7] 0 0
Canada
State/province [7] 0 0
Ontario
Country [8] 0 0
Canada
State/province [8] 0 0
Quebec
Country [9] 0 0
China
State/province [9] 0 0
Beijing
Country [10] 0 0
China
State/province [10] 0 0
Changchun
Country [11] 0 0
China
State/province [11] 0 0
Changsha
Country [12] 0 0
China
State/province [12] 0 0
Chengdu
Country [13] 0 0
China
State/province [13] 0 0
Chongqing
Country [14] 0 0
China
State/province [14] 0 0
Guangzhou
Country [15] 0 0
China
State/province [15] 0 0
Harbin
Country [16] 0 0
China
State/province [16] 0 0
Jining
Country [17] 0 0
China
State/province [17] 0 0
Shandong
Country [18] 0 0
China
State/province [18] 0 0
Shanghai
Country [19] 0 0
China
State/province [19] 0 0
Taiyuan
Country [20] 0 0
China
State/province [20] 0 0
Wuhan
Country [21] 0 0
China
State/province [21] 0 0
Xi'an
Country [22] 0 0
Czechia
State/province [22] 0 0
Brno
Country [23] 0 0
Czechia
State/province [23] 0 0
Olomouc
Country [24] 0 0
Czechia
State/province [24] 0 0
Praha
Country [25] 0 0
Hungary
State/province [25] 0 0
Budapest
Country [26] 0 0
Italy
State/province [26] 0 0
Milano
Country [27] 0 0
Italy
State/province [27] 0 0
Milan
Country [28] 0 0
Italy
State/province [28] 0 0
Modena
Country [29] 0 0
Italy
State/province [29] 0 0
Napoli
Country [30] 0 0
Italy
State/province [30] 0 0
Padova
Country [31] 0 0
Italy
State/province [31] 0 0
Roma
Country [32] 0 0
Japan
State/province [32] 0 0
Chuo-ku
Country [33] 0 0
Japan
State/province [33] 0 0
Koto-ku
Country [34] 0 0
Korea, Republic of
State/province [34] 0 0
Seoul
Country [35] 0 0
Poland
State/province [35] 0 0
Bydgoszcz
Country [36] 0 0
Poland
State/province [36] 0 0
Gdansk
Country [37] 0 0
Poland
State/province [37] 0 0
Gdynia
Country [38] 0 0
Poland
State/province [38] 0 0
Gliwice
Country [39] 0 0
Poland
State/province [39] 0 0
Grzepnica
Country [40] 0 0
Poland
State/province [40] 0 0
Kraków
Country [41] 0 0
Poland
State/province [41] 0 0
Lublin
Country [42] 0 0
Poland
State/province [42] 0 0
Torun
Country [43] 0 0
Poland
State/province [43] 0 0
Warszawa
Country [44] 0 0
Poland
State/province [44] 0 0
Lódz
Country [45] 0 0
Russian Federation
State/province [45] 0 0
Moscow
Country [46] 0 0
Spain
State/province [46] 0 0
Barcelona
Country [47] 0 0
Spain
State/province [47] 0 0
Madrid
Country [48] 0 0
Spain
State/province [48] 0 0
Málaga
Country [49] 0 0
Spain
State/province [49] 0 0
Pozuelo de Alarcon
Country [50] 0 0
Spain
State/province [50] 0 0
Sevilla
Country [51] 0 0
United Kingdom
State/province [51] 0 0
Cambridge
Country [52] 0 0
United Kingdom
State/province [52] 0 0
Manchester
Country [53] 0 0
United Kingdom
State/province [53] 0 0
Oxford
Country [54] 0 0
United Kingdom
State/province [54] 0 0
Sutton

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
Timothy Yap
Address 0 0
M.D. Anderson Cancer Center
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
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.