2023-508536-64-00招募中2 期
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)
适应症
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 50
- 试验地点
- 6
- 主要终点
- AZD5305 in combination with NHA: Number of participants with adverse events/ serious adverse events
研究概览
简要总结
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
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •For whole study: Age ≥ 18 at the time of screening.
- •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)
- •For whole study: Histologically confirmed diagnosis of metastatic prostate cancer.
- •For whole study: Candidate for treatment with enzalutamide, abiraterone acetate, darolutamide or apalutamide with documented current evidence of metastatic prostate cancer.
- •For whole study: Surgically or medically castrated.
- •For whole study: Adequate organ and marrow function.
- •For whole study: Eastern Cooperative Oncology Group Performance Status (ECOG PS): 0-1 with no deterioration over the previous 2 weeks.
- •For whole study: Life expectancy ≥ 16 weeks.
- •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.
- •For Patients Recruited Specifically to tumour Pharmacodynamic Cohorts: Patients must have at least 1 tumour suitable for paired biopsies
排除标准
- •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
- •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.
- •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).
- •For Part A mCRPC patients only: Patients recruited to the PDc cohorts should not have received a prior use of NHA.
- •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.
- •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
- •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.
- •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.
- •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).
- •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.
- •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.
- •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.
- •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
- •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.
- •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.
- •For Part A and Part B mCSPC Patients only: Any concurrent anticancer therapy or concurrent use of prohibited medications.
- •For Part A and Part B mCSPC Patients only: Major surgery within 4 weeks prior to the first dose of study treatment.
- •For Part A and Part B mCSPC Patients only: Radiotherapy within 4 weeks of the first dose of study treatment.
- •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.
- •For Part A and Part B mCSPC Patients only: Any history of persisting (> 2 weeks) severe pancytopenia.
- •For Part A and Part B mCSPC Patients only: Spinal cord compression, or brain metastases unless asymptomatic and treated and stable.
- •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).
- •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.
- •For Part A and Part B mCSPC Patients only: Any clinically significant cardiac disorders including QT prolongation, abnormal electrocardiogram (ECG).
- •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.
- •For Part A and Part B mCSPC Patients only: Patients with history of myelodysplastic syndrome (MDS)/ acute myeloid leukaemia (AML).
结局指标
主要结局
AZD5305 in combination with NHA: Number of participants with adverse events/ serious adverse events
AZD5305 in combination with NHA: Number of participants with adverse events/ serious adverse events
AZD5305 in combination with NHA: Number of participants with Dose Limiting Toxicities (DLTs) [Part A]
AZD5305 in combination with NHA: Number of participants with Dose Limiting Toxicities (DLTs) [Part A]
AZD5305 in combination with NHA: Changes from baseline in laboratory findings, physical examination, ECOG performance status, ECGs, and vital signs
AZD5305 in combination with NHA: Changes from baseline in laboratory findings, physical examination, ECOG performance status, ECGs, and vital signs
次要结局
- PK Parameters: (AZD5305 monotherapy): Area Under the concentration Curve (AUC) of AZD5305
- PK Parameters: (AZD5305 monotherapy): Maximum plasma concentration (Cmax) of AZD5305
- PK Parameters: (AZD5305 monotherapy): Time to maximum concentration (tmax) of AZD5305;
- PK Parameters: (AZD5305 in combination with NHA): AUC of AZD5305
- PK Parameters: (AZD5305 in combination with NHA): Cmax of AZD5305
- PK Parameters: (AZD5305 in combination with NHA): tmax of AZD5305;
- Efficacy parameters: Objective response rate (ORR)
- Efficacy parameters: Duration of response (DoR)
- Efficacy parameters: Time to response (TTR)
- Efficacy parameters: Radiographic progression-free survival (rPFS)
- Efficacy parameters: Percentage change in target lesion size
- Efficacy parameters: Proportion of participants with ≥ 50% PSA decrease
- Efficacy parameters: Proportion of participants with ≥ 90% PSA decrease
- Efficacy parameters: Proportion of patients with undetectable PSA (< 0.2 ng/mL) [Part B]
- Efficacy parameters: PSA progression free survival
- Efficacy parameters: Homologous recombination repair gene mutation (HRRRm) (including BRCA1/2) and their relationship with clinical response [Part B]
- [Part A] PK parameters of Enzalutamide and Apalutamide in combination with AZD5305: AUC of enzalutamide and apalutamide
- [Part A] PK parameters of Enzalutamide and Apalutamide in combination with AZD5305: Cmax of enzalutamide and apalutamide
- [Part A] PK parameters of Enzalutamide and Apalutamide in combination with AZD5305: tmax of enzalutamide and apalutamide
研究者
Information Center
Scientific
AstraZeneca AB
研究点 (6)
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