Study of AZD5305 When Given in Combination With New Hormonal Agents in Patients With Metastatic Prostate Cancer (PETRANHA)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AstraZeneca AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

17 May 2022 → ongoing

Decision date (initial)

2024-02-28

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

AstraZeneca AB

External identifiers

EU CT number

2023-508536-64-00

EudraCT number

2021-006289-19

ClinicalTrials.gov

NCT05367440

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Safety, Pharmacokinetic, Efficacy

To assess the safety and tolerability of AZD5305 when given in combination with new hormonal agents (NHA) (enzalutamide, abiraterone acetate, darolutamide, or apalutamide) to patients with metastatic prostate cancer

Secondary objectives 5

1. To characterise the Pharmacokinetic (PK) of AZD5305 monotherapy in plasma following a single dose and/or at steady state after multiple dosing when given orally as monotherapy and in combination with an NHA
2. To evaluate the effect of enzalutamide and apalutamide on the PK of AZD5305
3. To assess the preliminary antitumour activity of AZD5305 in combination with an NHA
4. To characterize the PK of enzalutamide and apalutamide in plasma at steady state when given orally in combination with AZD5305
5. To investigate the efficacy of AZD5305 in combination with an NHA according to biomarker subgroups defined from the tumour or circulating tumour deoxyribonucleic acid (ctDNA)

Conditions and MedDRA coding

Metastatic Prostate Cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. For whole study: Age ≥ 18 at the time of screening.
2. For whole study: Histologically confirmed diagnosis of metastatic prostate cancer.
3. For whole study: Candidate for treatment with enzalutamide, abiraterone acetate, darolutamide or apalutamide with documented current evidence of metastatic prostate cancer.
4. For whole study: Surgically or medically castrated.
5. For whole study: Adequate organ and marrow function.
6. For whole study: Eastern Cooperative Oncology Group Performance Status (ECOG PS): 0-1 with no deterioration over the previous 2 weeks.
7. For whole study: Life expectancy ≥ 16 weeks.
8. For whole study: 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.
9. For Patients Recruited Specifically to tumour Pharmacodynamic Cohorts: Patients must have at least 1 tumour suitable for paired biopsies
10. For Part A: Patients with Metastatic Castrate ion-Resistant Prostate Cancer (mCRPC) or Metastatic Castration Sensitive Prostate Cancer (mCSPC).
11. For Part B: Patients must have mCSPC (de novo or recurrent)

Exclusion criteria 26

1. For Part A mCRPC patients only: Any previous treatment with a new hormonal agent (NHA), poly (adenosine diphosphate–ribose) polymerase inhibitor (PARPi), Lutetium prostate-specific membrane antigen (Lu-PSMA), platinum chemotherapy
2. For Part A and Part B mCSPC Patients only: 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.
3. For Part A and Part B mCSPC Patients only: Any history of persisting (> 2 weeks) severe pancytopenia.
4. For Part A and Part B mCSPC Patients only: Spinal cord compression, or brain metastases unless asymptomatic and treated and stable.
5. For Part A and Part B mCSPC Patients only: 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).
6. For Part A and Part B mCSPC Patients only: Patients with any known predisposition to bleeding (eg, active peptic ulceration, recent [within 6 months] haemorrhagic stroke, proliferative diabetic retinopathy.
7. For Part A and Part B mCSPC Patients only: Any clinically significant cardiac disorders including QT prolongation, abnormal electrocardiogram (ECG).
8. For Part A and Part B mCSPC Patients only: Any clinically significant cardiovascular diseases including symptomatic heart failure, uncontrolled hypertension, acute coronary syndrome, cardiomyopathy, valvular heart disease, atrial fibrillation, stroke.
9. For Part A and Part B mCSPC Patients only: Patients with history of myelodysplastic syndrome (MDS)/ acute myeloid leukaemia (AML).
10. For Part A and Part B mCSPC Patients only: Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection.
11. For Part A and Part B mCSPC Patients only: Known allergy or hypersensitivity to investigational product(s) or any of the excipients of the investigational product(s).
12. For Part A mCRPC patients only: Patients recruited to the PDc cohorts should not have received a prior use of NHA.
13. For Part A and Part B mCSPC Patients only: Any condition that would interfere with evaluation of the study treatment or interpretation of patient safety or study results.
14. For Part A and Part B mCSPC Patients only: 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
15. For Part A and Part B mCSPC Patients only: 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.
16. For Part A and Part B mCSPC Patients only: 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.
17. For Part A and Part B mCSPC Patients only: 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).
18. For Part A and Part B mCSPC Patients only: 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.
19. For Part A and Part B mCSPC Patients only: Any previous treatment with a PARPi, platinum, NHA, Immuno-oncology (IO), radiopharmaceutical therapy, or prior treatment with docetaxel in mCSPC setting.
20. For Part A and Part B mCSPC Patients only: Concomitant use of medications or herbal supplements known to be: (a) Strong and moderate CYP3A4 inducers/inhibitors (applies for all arms) (b) For Arm 1 (enzalutamide) patients: Strong CYP2C8 inhibitors (c) For Arm 3 (darolutamide) patients: Strong P-glycoprotein inducers
21. For Part A and Part B mCSPC Patients only: Concomitant use of drugs that are known to prolong or shorten QT and have a known risk of Torsades de Pointes.
22. For Part A and Part B mCSPC Patients only: Treatment with any of the following: a) 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. b) 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. c) Any live virus or bacterial vaccine within 28 days of the first dose of study treatment.
23. For Part A and Part B mCSPC Patients only: Any concurrent anticancer therapy or concurrent use of prohibited medications.
24. For Part A and Part B mCSPC Patients only: Major surgery within 4 weeks prior to the first dose of study treatment.
25. For Part A and Part B mCSPC Patients only: Radiotherapy within 4 weeks of the first dose of study treatment.
26. For Part A and Part B mCSPC Patients only: 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. AZD5305 in combination with NHA: Number of participants with adverse events/ serious adverse events
2. AZD5305 in combination with NHA: Number of participants with Dose Limiting Toxicities (DLTs) [Part A]
3. AZD5305 in combination with NHA: Changes from baseline in laboratory findings, physical examination, ECOG performance status, ECGs, and vital signs

Secondary endpoints 19

1. PK Parameters: (AZD5305 monotherapy): Area Under the concentration Curve (AUC) of AZD5305
2. PK Parameters: (AZD5305 monotherapy): Maximum plasma concentration (Cmax) of AZD5305
3. PK Parameters: (AZD5305 monotherapy): Time to maximum concentration (tmax) of AZD5305;
4. PK Parameters: (AZD5305 in combination with NHA): AUC of AZD5305
5. PK Parameters: (AZD5305 in combination with NHA): Cmax of AZD5305
6. PK Parameters: (AZD5305 in combination with NHA): tmax of AZD5305;
7. Efficacy parameters: Objective response rate (ORR)
8. Efficacy parameters: Duration of response (DoR)
9. Efficacy parameters: Time to response (TTR)
10. Efficacy parameters: Radiographic progression-free survival (rPFS)
11. Efficacy parameters: Percentage change in target lesion size
12. Efficacy parameters: Proportion of participants with ≥ 50% PSA decrease
13. Efficacy parameters: Proportion of participants with ≥ 90% PSA decrease
14. Efficacy parameters: Proportion of patients with undetectable PSA (< 0.2 ng/mL) [Part B]
15. Efficacy parameters: PSA progression free survival
16. Efficacy parameters: Homologous recombination repair gene mutation (HRRRm) (including BRCA1/2) and their relationship with clinical response [Part B]
17. [Part A] PK parameters of Enzalutamide and Apalutamide in combination with AZD5305: AUC of enzalutamide and apalutamide
18. [Part A] PK parameters of Enzalutamide and Apalutamide in combination with AZD5305: Cmax of enzalutamide and apalutamide
19. [Part A] PK parameters of Enzalutamide and Apalutamide in combination with AZD5305: tmax of enzalutamide and apalutamide

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 7

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AstraZeneca AB

Sponsor organisation

AstraZeneca AB

Address

Astraallen Gartuna, Karlebyhus Byggnad 674 Karlebyhus Byggnad 674

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

AstraZeneca AB

Contact name

Information Center

Public contact point

Organisation

AstraZeneca AB

Contact name

Information Center

Locations

1 EU/EEA country · 6 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 22 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications