PETRANHA: Study of AZD5305 When Given in Combination With New Hormonal Agents in Patients With Metastatic Prostate Cancer
Study Details
Study Description
Brief Summary
This study will evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary efficacy of AZD5305 when given in combination with new hormonal agents (NHAs) in patients with Metastatic Prostate Cancer
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Detailed Description
Approximately 140 patients will be enrolled and screened to ensure that up to approximately 126 evaluable patients can be assigned to study treatments across all study arms (1 to 3).
Study treatment administration will continue until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study treatment occur.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| 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. |
Drug: AZD5305
Patients will receive an oral dose of AZD5305 once daily
Drug: Enzalutamide
Patients will receive an oral dose of Enzalutamide once daily
Other Names:
|
| 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. |
Drug: AZD5305
Patients will receive an oral dose of AZD5305 once daily
Drug: Abiraterone Acetate
Patients will receive an oral dose of Abiraterone Acetate once daily
Other Names:
|
| 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. |
Drug: AZD5305
Patients will receive an oral dose of AZD5305 once daily
Drug: Darolutamide
Patients will receive an oral dose of Darolutamide twice daily
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of patients with Adverse Events and Serious Adverse Events [Up to post treatment follow-up (28 days after last dose) [assessed up to 2.3 years]]
Number of patients with adverse events and with serious adverse events including abnormal clinical observations, abnormal ECG parameters, abnormal laboratory assessments and abnormal vital signs that changed from baseline will be assessed.
- Number of patients with Dose Limiting Toxicities (DLTs) [For Arm 1: 35 days, For Arm 2 and 3: 28 days]
To assess the safety and tolerability of AZD5305 when given in combination with NHA.
Secondary Outcome Measures
- Area Under the concentration Curve (AUC) of AZD5305 [At the end of Cycle 0 (Cycle 0 is of 7 days)]
To characterise the PK (AUC) of AZD5305 at steady state after multiple dosing of AZD5305 monotherapy.
- Maximum plasma concentration (Cmax) of AZD5305 [At the end of Cycle 0 (Cycle 0 is of 7 days)]
To characterise the PK (Cmax) of AZD5305 at steady state after multiple dosing of AZD5305 monotherapy.
- Time to maximum concentration (tmax) of AZD5305 [At the end of Cycle 0 (Cycle 0 is of 7 days)]
To characterise the PK (tmax) of AZD5305 at steady state after multiple dosing of AZD5305 monotherapy.
- AUC of AZD5305 [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)]
To characterise the PK (AUC) of AZD5305 following oral dose administration of AZD5305 in combination with NHA.
- Cmax of AZD5305 [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)]
To characterise the PK (Cmax) of AZD5305 following oral dose administration of AZD5305 in combination with NHA.
- tmax of AZD5305 [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)]
To characterise the PK (tmax) of AZD5305 following oral dose administration of AZD5305 in combination with NHA.
- Objective response rate (ORR) [From Screening (Day -28) to confirmed disease progression [assessed up to 2.3 years]]
To assess the preliminary antitumour activity of AZD5305 in combination with NHA. ORR will be assessed as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (soft tissue) and Prostate Cancer Clinical Trials Working Group 3 (PCWG3) and is defined as the percentage of patients who have a confirmed visit response of complete response (CR) or partial response (PR) in their soft tissue disease and no disease progression in their bone scan.
- Duration of response (DoR) [From Screening (Day -28) to confirmed disease progression [assessed up to 2.3 years]]
To assess the preliminary antitumour activity of AZD5305 in combination with NHA. DoR is defined as the time from the date of first documented response (which is subsequently confirmed) until date of documented progression or death in the absence of progressive disease (PD).
- Time to response (TTR) [From Screening (Day -28) to confirmed disease progression [assessed up to 2.3 years]]
To assess the preliminary antitumour activity of AZD5305 in combination with NHA. TTR is defined as the time from first dose until the first documentation of a subsequently confirmed objective response.
- Radiographic progression-free survival (rPFS) [From Screening (Day -28) to confirmed disease progression [assessed up to 2.3 years]]
To assess the preliminary antitumour activity of AZD5305 in combination with NHA. rPFS is defined as the time from start of first treatment until progression as per RECIST v1.1 (soft tissue) and PCWG3 criteria (bone) or death from any cause.
- Percentage change in tumour size [From Screening (Day -28) to confirmed disease progression [assessed up to 2.3 years]]
To assess the preliminary antitumour activity of AZD5305 in combination with NHA. Percentage change in tumour size will be determined for patients with measurable disease at baseline.
- Percentage of participants with > 50% prostate-specific antigen (PSA) decrease from baseline [From Screening (Day -28) to confirmed disease progression [assessed up to 2.3 years]]
To assess the preliminary antitumour activity of AZD5305 in combination with NHA.
- AUC of Enzalutamide [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)]
To characterize the PK (AUC) of Enzalutamide in plasma at steady state when given orally in combination with AZD5305
- Cmax of Enzalutamide [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)]
To characterize the PK (Cmax) of Enzalutamide in plasma at steady state when given orally in combination with AZD5305
- tmax of Enzalutamide [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)]
To characterize the PK (tmax) of Enzalutamide in plasma at steady state when given orally in combination with AZD5305
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Histologically confirmed diagnosis of metastatic prostate cancer.
-
Candidate for treatment with enzalutamide, abiraterone acetate, or darolutamide with documented current evidence of metastatic prostate cancer.
-
Surgically or medically castrated.
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Patients with Metastatic Castrate Resistant Prostate Cancer (mCRPC) or Metastatic Hormone Sensitive Prostate Cancer (mHSPC).
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Adequate organ and marrow function.
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Eastern Cooperative Oncology Group Performance Status (ECOG PS): 0-1 with no deterioration over the previous 2 weeks.
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Life expectancy ≥ 16 weeks.
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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.
Exclusion Criteria:
-
Concomitant use of medications or herbal supplements that may involve severe drug-drug interactions with the study treatment.
-
Concomitant use of drugs that are known to prolong or shorten QT and have a known risk of Torsades de Pointes.
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Treatment with any of the following:
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Any investigational agents or study interventions from a previous clinical study within 5 half lives or 3 weeks (whichever is shorter) of the first dose of study treatment.
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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.
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Any live virus or bacterial vaccine within 28 days of the first dose of study treatment.
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Any concurrent anticancer therapy or concurrent use of prohibited medications.
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Any previous treatment with a poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitor, Lu-PSMA, platinum chemotherapy, docetaxel (for mHSPC patients).
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Major surgery within 4 weeks prior to the first dose of study treatment.
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Radiotherapy within 4 weeks of the first dose of study treatment.
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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.
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Any history of persisting (> 2 weeks) severe pancytopenia.
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Spinal cord compression, or brain metastases unless asymptomatic and treated and stable.
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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).
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Patients with any known predisposition to bleeding (eg, active peptic ulceration, recent [within 6 months] haemorrhagic stroke, proliferative diabetic retinopathy).
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Any clinically significant cardiac disorders including QT prolongation, abnormal electrocardiogram (ECG).
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Any clinically significant cardiovascular diseases including symptomatic heart failure, uncontrolled hypertension, acute coronary syndrome, cardiomyopathy, valvular heart disease, atrial fibrillation, stroke.
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Patients with history of myelodysplastic syndrome (MDS)/ acute myeloid leukaemia (AML).
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Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection.
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Known allergy or hypersensitivity to investigational product(s) or any of the excipients of the investigational product(s).
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Any condition that would interfere with evaluation of the study treatment or interpretation of patient safety or study results.
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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.
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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.
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Arm 1 (Enzalutamide) only: 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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Research Site | Camperdown | Australia | 2050 | |
| 2 | Research Site | Darlinghurst | Australia | 2010 | |
| 3 | Research Site | East Melbourne | Australia | 3002 | |
| 4 | Research Site | Melbourne | Australia | 3000 | |
| 5 | Research Site | St. Leonards | Australia | 2065 | |
| 6 | Research Site | Cambridge | United Kingdom | CB2 0QQ | |
| 7 | Research Site | Glasgow | United Kingdom | G12 0YN | |
| 8 | Research Site | Hampshire | United Kingdom | SO16 6YD | |
| 9 | Research Site | Manchester | United Kingdom | M20 4BX | |
| 10 | Research Site | Newcastle Upon Tyne | United Kingdom | NE7 7JA | |
| 11 | Research Site | Plymouth | United Kingdom | PL6 8DH |
Sponsors and Collaborators
- AstraZeneca
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- D9720C00003
- 2021-006289-19