Phase III Study of Abiraterone Acetate (II) Versus Abiraterone Acetate in Patients with MCRPC

A Multicenter, Randomized Controlled Trial of Abiraterone Acetate (II) Combined with ADT Versus Abiraterone Acetate Combined with ADT in Patients with Metastatic Castration-resistant Prostate Cancer

Acetate abiraterone tablets (II) is a modified new drug launched in China, prepared using nanocrystal technology and supplemented with SNAC as an absorption enhancer, working together to promote the gastrointestinal absorption of Abiraterone, improve its oral bioavailability, and reduce its pharmacokinetic variability within individuals, as well as the impact of food on its pharmacokinetics. According to preliminary research results, the exposure to 300mg acetate abiraterone tablets (II) under fasting conditions is not less than the exposure to the original Zeke® 1000mg, and the food effect of acetate abiraterone tablets (II) is small, allowing for medication without dietary restrictions. The registration study uses steady-state serum testosterone levels as the primary pharmacodynamic indicator, comparing the efficacy of 300mg acetate Abiraterone tablets (II) and 1000mg Zeke® in mCRPC patients to be equivalent, with a safety advantage.This study is a non-inferior phase III, open-label, randomized controlled, multicenter trial. The study planned to enroll 400 mCRPC subjects and randomly assign them to the experimental group or the control group in a 1:1 ratio. The experimental group was treated with abiraterone acetate tablets (II.) combined with prednisone, and the control group was treated with abiraterone acetate tablets combined with prednisone, and the primary endpoints were PSA50 response rate and safety.To assess whether the efficacy (PSA50) of Abiraterone Acetate Tablets (II) is statistically non-inferior to that of Abiraterone Acetate Tablets, and whether there is a significant reduction in the incidence of grade 3 and above TEAEs.

Inclusion Criteria:

1. Age≧ 18 years old, male;

2. Physical condition ECOG score 0~1 points;

3. Expected survival of at least 6 months;

4. Prostate adenocarcinoma confirmed by histological or cytological examination, and no diagnosis of neuroendocrine carcinoma or small cell carcinoma;

5. Ongoing luteinizing hormone-releasing hormone-releasing hormone (LHRHA) therapy (medical castration) or prior bilateral orchiectomy (surgical castration); Subjects who have not undergone bilateral orchiectomy must plan to maintain effective LHRHA therapy throughout the study;

6. Testosterone at castration level (≦50 ng/dL or 1.73 nmol/L) at screening;

7. Disease progression at the time of study enrollment. Disease progression is defined as the occurrence of one or more of the following 3 items while the subject is receiving castration therapy: (1) PSA progression, defined as PSA > 1 ng/mL with a PSA interval of 1 week, 2 consecutive episodes of >50% increase from the baseline value; In patients treated with flutamide or bicalutamide, PSA must also progress after discontinuation (≧ 4 weeks and ≧6 weeks, respectively); (2) disease progression as defined in RECIST 1.1; (3) Bone disease progression as defined by PCWG3 criteria, i.e., more than ≧2 new lesions found on bone scan;

8. Subjects who have been treated with one endocrine drug and/or one cytotoxic chemotherapeutic drug in the hormone-sensitive stage, such as novel androgen receptor antagonists (such as enzalutamide, apalutamide, ODM-201, revilutamide, HC-1119 and proxalutamide) or ADT (such as goserelin), etc., subjects who have been treated ≤with more than one treatment (bicalutamide for 4 weeks in the mCRPC stage can be included, and subjects who are on a triple regimen of new endocrine therapy combined with docetaxel can be included, Dual subjects with docetaxel in combination with ADT may be included);

9. Metastatic lesions confirmed by CT/MRI or radioactive bone scan (99mTc) imaging examination;

10. The functional level of the organ must meet the following requirements (no blood transfusion or hematopoietic growth factor therapy within 2 weeks prior to routine blood screening):

    • ANC≧1.5×10*9/L；
    • PLT≧100×10*9/L；
    • Hb≧80 g/L；
    • TBIL≦1.0×ULN；
    • ALT and AST ≦2.5×ULN;
    • BUN and Cr≦1.5×ULN.

11. As judged by the investigator, be able to comply with the test protocol;

12. Male subjects whose partner is a female of childbearing potential, should be surgically sterile or agree to use effective contraception during the trial and for at least 3 weeks after the last administration of abiraterone acetate tablets (Ecente) or abiraterone acetate (II), sperm donation is not allowed during the study;

13. Voluntarily participate in this clinical trial, understand the study procedures and have signed informed consent.

Exclusion Criteria:

1. Previous treatment with abiraterone acetate for prostate cancer;
2. Have received ≥2-line systemic drug therapy in the hormone-sensitive stage in the past;
3. Prior treatment with novel androgen receptor antagonists (such as enzalutamide, apalutamide, ODM-201, revilutamide, HC-1119 and proxalutamide), any cytotoxic chemotherapy drug therapy, molecularly targeted therapy (patients with HRR mutations who refuse or are unable to use PARP inhibitors can be enrolled) or immunotherapy in the mCRPC stage;
4. The washout period of any prior anti-tumor therapy (including radiotherapy, surgery, molecularly targeted therapy, immunotherapy, and first-generation androgen receptor antagonists) to the end of the randomization date of this study is < 4 weeks (except for the bicalutamide washout period < 6 weeks);
5. Participate in other drug clinical trials as subjects, and the last test drug administration is within 4 weeks from the randomization date of the drug in this study;
6. Plan to receive any other anti-tumor therapy during this trial;
7. Known untreated central nervous system (CNS) metastases. Patients with a history of surgery or radiotherapy for brain metastases, if the disease has been stable for at least 8 weeks after treatment prior to enrollment and corticosteroid-free for at least 2 weeks prior to enrollment;
8. Severe bone injury caused by tumor bone metastasis judged by the investigator, including severe bone pain with poor control, pathological fractures and spinal cord compression of important parts that occurred in the past 6 months or are expected to occur in the near future;
9. Presence of contraindications to prednisone (corticosteroid) use, such as active infection or other conditions;
10. Presence of any chronic condition requiring treatment with corticosteroids administered at doses greater than "prednisone 5 mg, BID";
11. Habitual constipation or diarrhea, irritable bowel syndrome, inflammatory bowel disease; Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to the first dose of the drug; Those with abnormal gastrointestinal function, which may affect drug absorption as judged by the investigator;
12. Have a history of epilepsy, or have had diseases that can induce seizures within 12 months before C1D1 (including a history of transient ischemic attack, cerebral stroke, traumatic brain injury with impaired consciousness requiring hospitalization);
13. Uncontrolled hypertension. Subjects with a history of hypertension are allowed to participate in this study if they can effectively control their blood pressure through antihypertensive therapy;
14. Presence of active cardiac disease within 6 months prior to the randomization date of the study, including: severe/unstable angina, myocardial infarction, symptomatic congestive heart failure, left ventricular ejection fraction <50%, and ventricular arrhythmias requiring medication;
15. Other malignant tumors within 5 years before the randomization date of the study (except for carcinoma in situ that has been in complete remission and malignant tumors that have been judged to have progressed slowly by the investigator);
16. Patients with active HBV or HCV infection (HBV virus copy number≧ 10*4 copies/mL, HCV virus copy number≧10*3 copies/mL);
17. History of immunodeficiency (including HIV test positive, other acquired and congenital immunodeficiency diseases) or organ transplantation;
18. Presence of inability to swallow, chronic diarrhea, intestinal obstruction or other factors affecting drug taking and absorption;
19. Known allergy or intolerance to abiraterone acetate or its excipients;
20. According to the judgment of the investigator, there are concomitant diseases (such as severe diabetes, peripheral neuropathy, thyroid diseases and psychiatric disorders, etc.) or any other conditions that seriously endanger the safety of the patient or affect the completion of the study.