Register a trial

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05367440




Registration number
NCT05367440
Ethics application status
Date submitted
19/04/2022
Date registered
10/05/2022

Titles & IDs
Public title
Study of AZD5305 When Given in Combination With New Hormonal Agents in Patients With Metastatic Prostate Cancer
Scientific title
A Multi-arm, Open-label Phase I/IIa Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of AZD5305 in Combination With New Hormonal Agents in Patients With Metastatic Prostate Cancer (PETRANHA)
Secondary ID [1] 0 0
2021-006289-19
Secondary ID [2] 0 0
D9720C00003
Universal Trial Number (UTN)
Trial acronym
PETRANHA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Prostate Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - AZD5305
Treatment: Drugs - Enzalutamide
Treatment: Drugs - Abiraterone Acetate
Treatment: Drugs - Darolutamide
Treatment: Drugs - Apalutamide

Experimental: Arm 1 (AZD5305 in combination with enzalutamide) - Patients will receive an oral dose of AZD5305 and Enzalutamide once daily until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study treatment occur.

Experimental: Arm 2 (AZD5305 in combination with abiraterone acetate) - Patients will receive an oral dose of AZD5305 and Abiraterone Acetate once daily until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study treatment occur.

Experimental: Arm 3 (AZD5305 in combination with darolutamide) - Patients will receive an oral dose of AZD5305 once daily and Darolutamide twice daily until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study treatment occur.

Experimental: Arm 4 (AZD5305 in combination with apalutamide) - Patients will receive an oral dose of AZD5305 and Apalutamide once daily until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study treatment occur.


Treatment: Drugs: AZD5305
Patients will receive an oral dose of AZD5305 once daily

Treatment: Drugs: Enzalutamide
Patients will receive an oral dose of Enzalutamide once daily

Treatment: Drugs: Abiraterone Acetate
Patients will receive an oral dose of Abiraterone Acetate once daily

Treatment: Drugs: Darolutamide
Patients will receive an oral dose of Darolutamide twice daily

Treatment: Drugs: Apalutamide
Patients will receive an oral dose of Apalutamide once daily
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of patients with Adverse Events and Serious Adverse Events
Timepoint [1] 0 0
Up to post treatment follow-up (28 days after last dose) [assessed up to 2.3 years]
Primary outcome [2] 0 0
Part A: Number of patients with Dose Limiting Toxicities (DLTs)
Timepoint [2] 0 0
For Arm 1: 35 days, For Arm 2 and 3: 28 days
Secondary outcome [1] 0 0
Area Under the concentration Curve (AUC) of AZD5305
Timepoint [1] 0 0
At the end of Cycle 0 (Cycle 0 is of 7 days)
Secondary outcome [2] 0 0
Maximum plasma concentration (Cmax) of AZD5305
Timepoint [2] 0 0
At the end of Cycle 0 (Cycle 0 is of 7 days)
Secondary outcome [3] 0 0
Time to maximum concentration (tmax) of AZD5305
Timepoint [3] 0 0
At the end of Cycle 0 (Cycle 0 is of 7 days)
Secondary outcome [4] 0 0
AUC of AZD5305
Timepoint [4] 0 0
Arm 1: At Cycle 1 Day 1, Cycle 1 Day 22, Cycle 2 Day 1, Cycle 2 Day 2, Cycle 2 Day 8, and Cycle 3 Day 1; Arm 2 and 3: At Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 2 Day 1 (Each Cycle is of 28 days)
Secondary outcome [5] 0 0
Cmax of AZD5305
Timepoint [5] 0 0
Arm 1: At Cycle 1 Day 1, Cycle 1 Day 22, Cycle 2 Day 1, Cycle 2 Day 2, Cycle 2 Day 8, and Cycle 3 Day 1; Arm 2 and 3: At Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 2 Day 1 (Each Cycle is of 28 days)
Secondary outcome [6] 0 0
tmax of AZD5305
Timepoint [6] 0 0
Arm 1: At Cycle 1 Day 1, Cycle 1 Day 22, Cycle 2 Day 1, Cycle 2 Day 2, Cycle 2 Day 8, and Cycle 3 Day 1; Arm 2 and 3: At Cycle 1 Day 1, Cycle 1 Day 15 and Cycle 2 Day 1 (Each Cycle is of 28 days)
Secondary outcome [7] 0 0
Objective response rate (ORR)
Timepoint [7] 0 0
From Screening (Day -28) to confirmed disease progression [assessed up to 2.3 years]
Secondary outcome [8] 0 0
Duration of response (DoR)
Timepoint [8] 0 0
From Screening (Day -28) to confirmed disease progression [assessed up to 2.3 years]
Secondary outcome [9] 0 0
Time to response (TTR)
Timepoint [9] 0 0
From Screening (Day -28) to confirmed disease progression [assessed up to 2.3 years]
Secondary outcome [10] 0 0
Radiographic progression-free survival (rPFS)
Timepoint [10] 0 0
From Screening (Day -28), 12 months, 24 months and up to confirmed disease progression [assessed up to 2.3 years]
Secondary outcome [11] 0 0
Percentage change in tumour size
Timepoint [11] 0 0
From Screening (Day -28) to confirmed disease progression [assessed up to 2.3 years]
Secondary outcome [12] 0 0
Number of patients with = 50% prostate-specific antigen (PSA) decrease from baseline
Timepoint [12] 0 0
From Screening (Day -28) to confirmed disease progression [assessed up to 2.3 years]
Secondary outcome [13] 0 0
Number of patients with = 90% prostate-specific antigen (PSA) decrease from baseline
Timepoint [13] 0 0
From Screening (Day -28) to confirmed disease progression [assessed up to 2.3 years]
Secondary outcome [14] 0 0
Part B: Number of patients with undetectable PSA (< 0.2 ng/mL)
Timepoint [14] 0 0
3, 6, 9 and 12 months
Secondary outcome [15] 0 0
PSA Progression-free survival
Timepoint [15] 0 0
6, 12, 18, 24 and 30 months
Secondary outcome [16] 0 0
AUC of Enzalutamide
Timepoint [16] 0 0
At Cycle 1 Day 22, Cycle 2 Day 1, Cycle 2 Day 2, Cycle 2 Day 8 and Cycle 3 Day 1 (Each Cycle is of 28 days)
Secondary outcome [17] 0 0
Cmax of Enzalutamide
Timepoint [17] 0 0
At Cycle 1 Day 22, Cycle 2 Day 1, Cycle 2 Day 2, Cycle 2 Day 8 and Cycle 3 Day 1 (Each Cycle is of 28 days)
Secondary outcome [18] 0 0
tmax of Enzalutamide
Timepoint [18] 0 0
At Cycle 1 Day 22, Cycle 2 Day 1, Cycle 2 Day 2, Cycle 2 Day 8 and Cycle 3 Day 1 (Each Cycle is of 28 days)
Secondary outcome [19] 0 0
AUC of Apalutamide
Timepoint [19] 0 0
At Cycle 1 Day 22, Cycle 2 Day 1, Cycle 2 Day 2, Cycle 2 Day 8 and Cycle 3 Day 1 (Each Cycle is of 28 days)
Secondary outcome [20] 0 0
Cmax of Apalutamide
Timepoint [20] 0 0
At Cycle 1 Day 22, Cycle 2 Day 1, Cycle 2 Day 2, Cycle 2 Day 8 and Cycle 3 Day 1 (Each Cycle is of 28 days)
Secondary outcome [21] 0 0
tmax of Apalutamide
Timepoint [21] 0 0
At Cycle 1 Day 22, Cycle 2 Day 1, Cycle 2 Day 2, Cycle 2 Day 8 and Cycle 3 Day 1 (Each Cycle is of 28 days)
Secondary outcome [22] 0 0
Part B: Homologous recombination repair gene mutation (HRRRm)
Timepoint [22] 0 0
From Screening (Day -28) to confirmed disease progression [assessed up to 2.3 years]

Eligibility
Key inclusion criteria
For whole study:

* Age = 18 at the time of screening.
* Histologically confirmed diagnosis of metastatic prostate cancer.
* Candidate for treatment with enzalutamide, abiraterone acetate, darolutamide or apalutamide with documented current evidence of metastatic prostate cancer.
* Surgically or medically castrated.
* Adequate organ and marrow function.
* Eastern Cooperative Oncology Group Performance Status (ECOG PS): 0-1 with no deterioration over the previous 2 weeks.
* Life expectancy = 16 weeks.
* Non-sterilized male patients who are sexually active with a female partner of childbearing potential must use a condom with spermicide from screening to approximately 6 months after the last dose of study treatment .

For Patients Recruited Specifically to tumour Pharmacodynamic Cohorts:

• Patients must have at least 1 tumour suitable for paired biopsies

For Part A:

• Patients with Metastatic Castrate ion-Resistant Prostate Cancer (mCRPC) or Metastatic Castration Sensitive Prostate Cancer (mCSPC).

For Part B:

• Patients must have mCSPC (de novo or recurrent) with a baseline PSA value of = 0.2 ng/mL
Minimum age
18 Years
Maximum age
130 Years
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
For Part A mCRPC patients only:

* Any previous treatment with a new hormonal agent (NHA), poly (adenosine diphosphateribose) polymerase inhibitor (PARPi), Lutetium prostate-specific membrane antigen (Lu-PSMA), platinum chemotherapy
* Patients recruited to the PDc cohorts should not have received a prior use of new hormonal agents (NHA).

For Part A and Part B mCSPC Patients:

* Any previous treatment with a PARPi, platinum, NHA, Immuno-oncology (IO), radiopharmaceutical therapy, or prior treatment with docetaxel in mCSPC setting.
* Concomitant use of medications or herbal supplements known to be:

1. Strong and moderate CYP3A4 inducers/inhibitors (applies for all arms)
2. For Arm 1 (enzalutamide) patients: Strong CYP2C8 inhibitors
3. For Arm 3 (darolutamide) patients: Strong P-glycoprotein inducers
* Concomitant use of drugs that are known to prolong or shorten QT and have a known risk of Torsades de Pointes.
* Treatment with any of the following:

1. Any investigational agents or study interventions from a previous clinical study within 5 half lives or 3 weeks (whichever is longer) of the first dose of study treatment.
2. Any other anticancer treatment within the following time periods prior to the first dose of study treatment: (i) Cytotoxic and non-cytotoxic treatment: 3 weeks or 5 half-lives (whichever is shorter). (ii) Biological products including immuno-oncology agents: 4 weeks before enrolment.
3. Any live virus or bacterial vaccine within 28 days of the first dose of study treatment.
* Any concurrent anticancer therapy or concurrent use of prohibited medications.
* Major surgery within 4 weeks prior to 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.
* With the exception of alopecia, and peripheral neuropathy; any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 at the time of study enrolment.
* Any history of persisting (> 2 weeks) severe pancytopenia.
* Spinal cord compression, or brain metastases unless asymptomatic and treated and stable.
* Any evidence of severe or uncontrolled systemic diseases, including, active bleeding diatheses, or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV).
* Patients with any known predisposition to bleeding (eg, active peptic ulceration, recent [within 6 months] haemorrhagic stroke, proliferative diabetic retinopathy.
* Any clinically significant cardiac disorders including QT prolongation, abnormal electrocardiogram (ECG).
* Any clinically significant cardiovascular diseases including symptomatic heart failure, uncontrolled hypertension, acute coronary syndrome, cardiomyopathy, valvular heart disease, atrial fibrillation, stroke.
* Patients with history 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.
* Known allergy or hypersensitivity to investigational product(s) or any of the excipients of the investigational product(s).
* Any condition that would interfere with evaluation of the study treatment or interpretation of patient safety or study results.
* Uncontrolled intercurrent illness within the last 12 months, including but not limited to, active interstitial lung disease, serious chronic gastrointestinal (GI) conditions associated with diarrhoea, or psychiatric illness/social situations
* History of another primary malignancy except for malignancy treated with curative intent with no known active disease within 3 years before the first dose of study treatment and of low potential risk for recurrence.
* Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.
* Arm 1 (Enzalutamide) and Arm 4 (Apalutamide): History of seizure or any condition that may predispose to seizure (eg, prior cortical stroke, significant brain trauma).
* Arm 2 (Abiraterone acetate) only: (i) Active infection or other medical condition that would contraindicate the use of systemic steroids (prednisone/prednisolone). (ii) Low serum potassium (< 3.5 mmol/L). (iii) History of uncontrolled pituitary or adrenal dysfunction.
* Arm 4 (Apalutamide): (i) Moderate or severe skin conditions or diseases that could affect the skin (eg. scleroderma, lupus). (ii) Any skin or medical condition that in the Investigator's opinion could increase the risk of skin toxicity.

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
Parallel
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
2/06/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
15/08/2030
Actual
Sample size
Target
172
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Camperdown
Recruitment hospital [2] 0 0
Research Site - Darlinghurst
Recruitment hospital [3] 0 0
Research Site - East Melbourne
Recruitment hospital [4] 0 0
Research Site - Heidelberg
Recruitment hospital [5] 0 0
Research Site - Melbourne
Recruitment hospital [6] 0 0
Research Site - St. Leonards
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [3] 0 0
3002 - East Melbourne
Recruitment postcode(s) [4] 0 0
3084 - Heidelberg
Recruitment postcode(s) [5] 0 0
3004 - Melbourne
Recruitment postcode(s) [6] 0 0
2065 - St. Leonards
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
Indiana
Country [3] 0 0
United States of America
State/province [3] 0 0
Michigan
Country [4] 0 0
United States of America
State/province [4] 0 0
New York
Country [5] 0 0
United States of America
State/province [5] 0 0
Pennsylvania
Country [6] 0 0
United States of America
State/province [6] 0 0
South Carolina
Country [7] 0 0
United States of America
State/province [7] 0 0
Texas
Country [8] 0 0
Italy
State/province [8] 0 0
Candiolo
Country [9] 0 0
Italy
State/province [9] 0 0
Milano
Country [10] 0 0
Italy
State/province [10] 0 0
Orbassano
Country [11] 0 0
Italy
State/province [11] 0 0
Padova
Country [12] 0 0
Italy
State/province [12] 0 0
Pavia
Country [13] 0 0
United Kingdom
State/province [13] 0 0
Cambridge
Country [14] 0 0
United Kingdom
State/province [14] 0 0
Glasgow
Country [15] 0 0
United Kingdom
State/province [15] 0 0
Hampshire
Country [16] 0 0
United Kingdom
State/province [16] 0 0
Manchester
Country [17] 0 0
United Kingdom
State/province [17] 0 0
Newcastle Upon Tyne
Country [18] 0 0
United Kingdom
State/province [18] 0 0
Plymouth

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AstraZeneca
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Bayer
Address [1] 0 0
Country [1] 0 0

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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
When will data be available (start and end dates)?
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.
Available to whom?
When a request has been approved AstraZeneca will provide access to the de-identified 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.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://astrazenecagroup-dt.pharmacm.com/DT/Home


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/NCT05367440