Clinical trial NCT05405439: To Evaluate the Efficacy of TQB3823 Combined With Abiraterone and Prednisone in Metastatic Castration-resistant Prostate Cancer Patientsprednisone Acetate Tablets in Patients With Metastatic Castration-resistant Prostate Cancer
Official title: Phase Ib/II Clinical Study of TQB3823 Tablets Combined With Abiraterone Acetate Tablets and Prednisone Acetate Tablets in Patients With Metastatic Castration-resistant Prostate Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Metastatic Castration-resistant Prostate Cancer
Lead sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2022-06-06
Enrollment: 39
Sex: MALE
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a phase Ib/II clinical study to explore the safety and efficacy of TQB3823 tablets combined with abiraterone acetate tablets and prednisone acetate tablets in patients with metastatic castration-resistant prostate cancer.

Detailed description: This is a two-phase, open-label Phase Ib clinical trial. The first phase plans to enroll 6-12 patients as two cohorts to explore the safety and of TQB3823 tablets combined with abiraterone and prednisone and the recommended dose of phase II of TQB3823. Subjects involved in cohort one accepts TQB3823 treatment during cycle one and then TQB3823 combined with abiraterone and prednisone from cycle two till the disease progression. The second phase plans to enroll a total of 40-60 subjects, aiming to evaluate the safety and efficacy of TQB3823 tablets combined with abiraterone and prednisone.

Eligibility criteria: Inclusion Criteria:

* Male patients aged 18 to 85.
* Subjects with pathologically proven with prostate adenocarcinoma.
* Metastatic disease confirmed by imaging (eg, bone scan and CT/MRI).
* The patient's serum testosterone level at the screening visit was ≤ 1.73 nmol/L (50 ng/dL). Patients who did not undergo bilateral orchiectomy required continued ADT \[gonadotropin-releasing hormone analog (LHRHa, agonist/antagonist)\] treatment throughout the study period.
* Disease progression during consecutive androgen deprivation therapy (ADT), defined at study entry, as meeting one or more of the following criteria:

  1. At least two consecutive PSA elevations separated by at least 1 week, the last result must be at least 1.0 ng/mL.
  2. Soft tissue lesion progression as assessed by RECIST 1.1 with or without PSA progression.
  3. Bone disease progression assessed by PCWG3, i.e., ≥2 new lesions detected on bone scan, ≥2 new bone lesions other than those previously assessed on reassessment at least 8 weeks later, with ≥2 previously assessed bone lesions still exist, regardless of PSA progression.
* Patients must discontinue all prior cancer therapy (except ADT and bone loss prophylaxis) and have recovered to ≤ Grade 1 or baseline (according to the Common Terminology Criteria for Adverse Events) prior to first dose of all acute toxic effects of prior therapy or surgery Version 5.0 \[CTCAE v 5.0\]), with the exception of alopecia and peripheral neuropathy, and the washout period since the last prior systemic or radiation therapy was as follows:

  1. At least 4 weeks must have elapsed since enrollment with 5-alpha reductase inhibitors (eg, dutasteride, finasteride), estrogen, and cyproterone.
  2. At least 4 weeks must have elapsed from major surgery or radiation therapy to enrollment。
* Laboratory indicators meet the requirements.

Exclusion Criteria:

* For subjects with brain metastases with symptoms or symptom control for less than 1 month, screening for CNS metastases at baseline is not required unless there are signs and/or symptoms of CNS involvement.
* Subjects who have developed or is currently suffering from other malignancies within 3 years, except for cured skin basal cell carcinoma and cervical carcinoma in situ.
* Subjects who have accepted botanicals (such as saw palmetto) that may lower PSA levels within 4 weeks before the first dose.
* Subjects who have accepted oral targeted drugs within 5 drug half-lives from the first dose (calculated from the end of the last treatment).
* Subjects who have not recovered to ≤ Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 due to the adverse event of prior therapy.
* Subjects who have previously accepted CYP17 enzyme inhibitors (including drugs such as abiraterone, TAK-700, TOK-001, and ketoconazole, ect.,) or second generation androgen receptor inhibitors (including enzalutamide, apalutamide, darolutamide , etc.) (mHSPC, nmCRPC stage).

  1. The study accept patients who received McRpc-based chemotherapy with CYP17 inhibitors other than abiraterone or second-generation androgen receptor inhibitors or paclitaxel for less than 3 months without disease progression, However, 4 weeks or 5 half-life washing out period is required (whichever is longer).
  2. Patients who received abiraterone in the mCRPC phase for less than 3 months and did not progress (no need to stop elution) are allowed in the study, but cannot be enrolled in the phase I cohort of a single drug population in this study.
  3. Patients who received ADT+ paclitaxel chemotherapy, ADT+ 1st generation androgen receptor inhibitors (e.g. Flutamide, bicalutamide, nilutamide, etc.), ADT+ERBT (external radiation therapy) in mHSPC phase will be acceptable in the study, provided that they met the exclusion criteria 2.
* Subjects who receive medications known to be potent inhibitors of cytochrome P450 3A4 (CYP3A4) or potent or moderate inducers and unable to discontinue these medications or switch to another for at least 5 half-lives prior to initiation of study medication different medicines.
* Subjects who suffer from contraindications to prednisone (corticosteroid) use, such as active systemic infection (e.g. bacterial infection requiring intravenous antibiotics at initiation of study treatment, fungal infection, or detectable viral infection requiring systemic therapy ) or viral load (e.g. known HIV positive or known active hepatitis B or C (e.g. hepatitis B surface antigen positive). Screening for contraindications other than HIV/HBV and HCV is not required to determine eligibility.
* Subjects with history of idiopathic pulmonary fibrosis, organizing pneumonia (eg, bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on a chest CT scan during screening.
* Subjects with any chronic condition requiring corticosteroid treatment at doses greater than "Prednisone 5mg, BID";

Primary outcomes:
measure: Dose limiting toxicity (DLT)
timeFrame: Up to 4 weeks
measure: Recommended phase II dose (RP2D)
timeFrame: Up to 8 weeks
measure: The ratio of subject radiographic progression-free survival for 12 months
timeFrame: For 12 months
measure: Adiographic progression-free survival (rPFS)
timeFrame: Up to 24 months
Secondary outcomes:
measure: The ratio of subject radiographic progression-free survival for 12 months
timeFrame: For 6 months
measure: The ratio of prostate specific antigen (PSA) reduction
timeFrame: Up to 24 months
measure: Overall response rate (ORR) based on 2014 Lugano
timeFrame: Up to 24 months
measure: Overall survival (OS)
timeFrame: Up to death
measure: Clinical benefit rate (CBR)
timeFrame: Up to 24 months
measure: Duration of Response (DOR)
timeFrame: Up to 24 months
measure: time to bone-related event
timeFrame: Up to 24 months
measure: Time to PSA progression
timeFrame: Up to 24 months
measure: Peak time (Tmax)
timeFrame: Cycle 1 day 1 and cycle 1 day 28 Before administration, and 1, 2, 4, 6, 8, 11, 12, 24 hours after administration. Cycle 1 day 14 before administration,(each cycle is 28 days)
measure: Peak concentration (Cmax)
timeFrame: Cycle 1 day 1 and cycle 1 day 28 Before administration, and 1, 2, 4, 6, 8, 11, 12, 24 hours after administration. Cycle 1 day 14 before administration,(each cycle is 28 days)
measure: Half-life /T1/2
timeFrame: Cycle 1 day 1 and cycle 1 day 28 Before administration, and 1, 2, 4, 6, 8, 11, 12, 24 hours after administration. Cycle 1 day 14 before administration,(each cycle is 28 days)
measure: Adverse event rate
timeFrame: Baseline up to 96 weeks
measure: Adverse event rate
timeFrame: Baseline up to 24 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: The First Hospital of Peking University
state: Beijing
city: Chongqing
country: China
facility: The Southwest Hospitai of Amu
state: Chongqing
city: Chongqing
country: China
facility: Chongqing Cancer Hospital
state: Chongqing
city: Lanzhou
country: China
facility: The Second Hospital of Harbin Medical University
state: Gansu
city: Guangzhou
country: China
facility: Sun Yat-Sun University Cancer Prevertion and Treatment Center
state: Guangdong
city: Qingyuan
country: China
facility: Qingyuan People's Hospital
state: Guangdong
city: Nanning
country: China
facility: The First Affiliated Hospital of Guangxi Medical University
state: Guangxi
city: Harbin
country: China
facility: Affiliated Cancer Hospital of Harbin Medical University
state: Heilongjiang
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Nanjing
country: China
facility: Jiangsu Province Hospital
state: Jiangsu
city: Shenyang
country: China
facility: Shengjing Hospital Affiliated to China Medical University
state: Liaoning
city: Jinan
country: China
facility: Shandong Cancer Hospital
state: Shandong
city: Shanghai
country: China
facility: Huadong Hospital Affiliated to Fudan University
state: Shanghai
city: Xi'an
country: China
facility: The First Affiliated Hospital of The Chinese People's Liberation Army Air Force Military Medical University
state: Shanxi
city: Chengdu
country: China
facility: West China Hospital，Sichuan University
state: Sichuan
city: Chengdu
country: China
facility: Sichuan Provincial People's Hospital
state: Sichuan
city: Luzhou
country: China
facility: The Affiliated Hospital of Southwest Medical University
state: Sichuan
city: Mianyang
country: China
facility: Mianyang Central Hospital
state: Sichuan
city: Zigong
country: China
facility: Zigong Fourth People's Hospital
state: Sichuan
city: Tianjin
country: China
facility: Cancer Hospital of Tianjin Medical University
state: Tianjin
city: Kunming
country: China
facility: The First Affiliated Hospital of Kunming Medical University
state: Yunnan
city: Kunming
country: China
facility: Second Affiliated Hospital of Kunming Medical University
state: Yunnan
city: Wenzhou
country: China
facility: The First Affiliated Hospital of Wenzhou Medical Univerity
state: Zhejiang
Study officials:
References: