Back to resultsNeoadjuvant Therapy of Abiraterone Plus ADT for Intraductal Carcinoma of the Prostate
Primary Purpose
Prostate Cancer
Status
Not yet recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Abiraterone acetate
Prednisolone
Goserelin
Sponsored by
About this trial
This is an interventional treatment trial for Prostate Cancer focused on measuring abiraterone acetate
Eligibility Criteria
Inclusion Criteria:
- Age ≥ 18 years
- Histologically or cytologically diagnosis of prostate cancer with positive IDC-P status
- High-risk localized prostate cancer, defined by either: Tumor stage ≥T3a by digital rectal examination, or Primary tumor Gleason score ≥ 8, or PSA > 20 ng/mL
- No evidence of metastases
- The ECOG score of the patient is ≤2
- Expected survival over 5 years
- Patients must participate voluntarily and sign an informed consent form (ICF), indicating that they understand the purpose and required procedures of the study, and are willing to participate in. Patients must be willing to obey the prohibitions and restrictions specified in the research protocol
- Agree to collect the tumor tissue and blood samples needed for the research and apply them to related study
Adequate hematologic, renal and hepatic function:
- Absolute neutrophil count [ANC] ≥1.5 x 10^9/L
- Platelet count [PLT] ≥100 x 10^9/L
- Hemoglobin [HGB] ≥9 g/dL
- Serum Total bilirubin [TBIL] ≤1.5 x upper limit of normal (ULN)
- Aspartate aminotransferase (AST), alanine aminotransferase (ALT) < 2.5 x ULN
- Serum albumin [ALB] ≥2.8 g/dL
- Serum Creatinine ≤ 1.5 x ULN
- Creatinine Clearance ≥ 40 mL/min
Exclusion Criteria:
- Prior androgen deprivation therapy (medical or surgical), radiation therapy or chemotherapy for prostate cancer
- Evidence of metastatic disease (M1) on imaging studies
- Pathological finding consistent with small cell, ductal or neuroendocrine carcinoma of the prostate
- Major surgery or severe trauma within 30 days before enrollment
Patients with severe or uncontrolled concurrent，including but not limited to：
- Severe or uncontrolled concurrent infections
- Human immunodeficiency virus [HIV] infection positive
- Suffer from acute or chronic active hepatitis B (HBsAg positive and HBV DNA>1x10^3/mL) Or acute or chronic active hepatitis C (HCV antibody positive and HCV RNA>15 IU/mL)
- Active tuberculosis, etc
- Abnormal cardiac function as manifested by NYHA (New York Heart Association) class III or IV heart failure，or clinically significant ventricular arrhythmias
- Uncontrolled hypertension（Systolic blood pressure≥160mmHg or Diastolic blood pressure≥100mmHg）
- Severe or unstable angina, myocardial infarction，arterial or venous thromboembolic events (eg, pulmonary embolism, cerebrovascular accident including transient ischemic attacks) Occurred within 6 months before enrollment
- Evidence of serious and/or unstable pre-existing medical, psychiatric or other condition (including laboratory abnormalities) that could interfere with patient safety or provision of informed consent to participate in this study
- Any condition that in the opinion of the investigator, would preclude participation in this study
Sites / Locations
- West China Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
ADT with Abiraterone and prednisone
Arm Description
All subjects in this arm will receive luteinizing hormone releasing hormone analogue (LHRHa) plus abiraterone acetate and prednisone, as per standard of care. Goserelin 10.8 mg will be used once per 12 weeks. Abiraterone acetate will be administered orally as 1000 mg once daily along with 5 mg of oral prednisone once per day. Subjects will continue to take abiraterone acetate and prednisone for 24 weeks before radical prostatectomy
Outcomes
Primary Outcome Measures
Pathologic Complete Response Rate（pCR）
The proportion of subjects with no morphologically recognizable cancer cell in tumor specimens after radical prostatectomy.
Secondary Outcome Measures
Rate of Subjects With Minimal Residual Disease
The proportion of subjects that have residual tumors with maximum diameter of 5 mm or less after radical prostatectomy.
Rate of positive surgical margin (PSM)
The rate of positive surgical margins in the prostatectomy specimen after neoadjuvant therapy.
Rate of Nodal Metastases After 6 Months of Treatment
The rate of the presence of tumor cells within surgically excised lymph nodes will be assessed after 6 months of neoadjuvant treatment.
Rate of Pathologic T3 Disease After 6 Months of Treatment
The rate of the presence of T3 disease (e.g. extraprostatic tumor not invading adjacent structures) will be determine from the prostatectomy specimen after 6 months of neoadjuvant treatment.
Biochemical Progression-free Survival (bPFS)
Biochemical progression will be defined per the American Urological Association guidelines (i.e. confirmed prostate-specific antigen post-radical prostatectomy >= 0.2 ng/mL) or death. Will be estimated using Kaplan-Meier methods and 95% CI will be estimated using Greenwood's formula.
PSA decline rate
The rate of PSA decline to baseline PSA after 6 months of neoadjuvant therapy.
Incidence and severity of adverse events
Safety as assessed by the incidence and severity of adverse events and serious adverse events graded according to the National Cancer Institute - Common Terminology Criteria for adverse events (CTCAE) version 4.0.
Quality of life (QOL) as assessed by FACT-P
The QOL will be measured using the functional assessment of cancer therapy-prostate（FACT-P）. The questionnaires will be administered at baseline, prior to RP and every 3 months for 2 years post RP.
Quality of life as assessed by EQ-5D
The QOL will be measured using the EuroQol five dimensions questionnaire（EQ-5D）. The questionnaires will be administered at baseline, prior to RP and every 3 months for 2 years post RP.
Radiographic progression-free survival (rPFS)
Time from surgery to radiographic progression or death
Overall survival
Time from surgery to death due to any cause
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04736108
Brief Title
Neoadjuvant Therapy of Abiraterone Plus ADT for Intraductal Carcinoma of the Prostate
Official Title
A Single-center, Phase II Neoadjuvant Study of Abiraterone Acetate in the Treatment of Intraductal Carcinoma of the Prostate
Study Type
Interventional
2. Study Status
Record Verification Date
February 2021
Overall Recruitment Status
Not yet recruiting
Study Start Date
May 2021 (Anticipated)
Primary Completion Date
October 2022 (Anticipated)
Study Completion Date
December 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
West China Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
Neoadjuvant treatment before radical prostatectomy has been proven to provide benefits on peri-operation results, especially on reduction of tumor volume and minimization of biochemical recurrence. This study will evaluate the efficacy and safety of abiraterone acetate Plus androgen deprivation therapy（ADT）in high-risk localized prostate cancer with intraductal carcinoma of the prostate（IDC-P）.
Detailed Description
IDC-P is an adverse pathological entity of prostate cancer, characterized by the growth of malignant cells in pre-existing prostatic ducts and acini, and is present in high-grade disease and associated with poor prognosis. Previous studies have shown that IDC-P was significantly associated with an adverse clinical course in patients who received radical prostatectomy or radiotherapy, and the presence of IDC-P on the biopsy specimen was associated with a poor prognosis in terms of overall survival (OS) and a poor docetaxel response in patients with distant metastasis at the initial diagnosis. Our previous researches as well as other published data indicated that abiraterone had a better therapeutic efficacy than docetaxel as the first-line therapy in metastatic castration resistance prostate cancer（mCRPC）with IDC-P. Therefore we intended to perform this single-arm phase II clinical trial to evaluate the initial efficacy and safety of abiraterone acetate Plus ADT as neoadjuvant therapy for high-risk localized prostate cancer with IDC-P. The primary endpoint is the pathologic complete response (pCR).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Cancer
Keywords
abiraterone acetate
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
50 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
ADT with Abiraterone and prednisone
Arm Type
Experimental
Arm Description
All subjects in this arm will receive luteinizing hormone releasing hormone analogue (LHRHa) plus abiraterone acetate and prednisone, as per standard of care. Goserelin 10.8 mg will be used once per 12 weeks. Abiraterone acetate will be administered orally as 1000 mg once daily along with 5 mg of oral prednisone once per day. Subjects will continue to take abiraterone acetate and prednisone for 24 weeks before radical prostatectomy
Intervention Type
Drug
Intervention Name(s)
Abiraterone acetate
Intervention Description
1000 mg orally daily for 24 weeks before radical prostatectomy
Intervention Type
Drug
Intervention Name(s)
Prednisolone
Intervention Description
5 mg oral low dose prednisone, once daily
Intervention Type
Drug
Intervention Name(s)
Goserelin
Intervention Description
10.8 mg goserelin hypodermic once per 12 weeks
Primary Outcome Measure Information:
Title
Pathologic Complete Response Rate（pCR）
Description
The proportion of subjects with no morphologically recognizable cancer cell in tumor specimens after radical prostatectomy.
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Rate of Subjects With Minimal Residual Disease
Description
The proportion of subjects that have residual tumors with maximum diameter of 5 mm or less after radical prostatectomy.
Time Frame
6 months
Title
Rate of positive surgical margin (PSM)
Description
The rate of positive surgical margins in the prostatectomy specimen after neoadjuvant therapy.
Time Frame
6 months
Title
Rate of Nodal Metastases After 6 Months of Treatment
Description
The rate of the presence of tumor cells within surgically excised lymph nodes will be assessed after 6 months of neoadjuvant treatment.
Time Frame
6 months
Title
Rate of Pathologic T3 Disease After 6 Months of Treatment
Description
The rate of the presence of T3 disease (e.g. extraprostatic tumor not invading adjacent structures) will be determine from the prostatectomy specimen after 6 months of neoadjuvant treatment.
Time Frame
6 months
Title
Biochemical Progression-free Survival (bPFS)
Description
Biochemical progression will be defined per the American Urological Association guidelines (i.e. confirmed prostate-specific antigen post-radical prostatectomy >= 0.2 ng/mL) or death. Will be estimated using Kaplan-Meier methods and 95% CI will be estimated using Greenwood's formula.
Time Frame
2 years
Title
PSA decline rate
Description
The rate of PSA decline to baseline PSA after 6 months of neoadjuvant therapy.
Time Frame
6 months
Title
Incidence and severity of adverse events
Description
Safety as assessed by the incidence and severity of adverse events and serious adverse events graded according to the National Cancer Institute - Common Terminology Criteria for adverse events (CTCAE) version 4.0.
Time Frame
6 months
Title
Quality of life (QOL) as assessed by FACT-P
Description
The QOL will be measured using the functional assessment of cancer therapy-prostate（FACT-P）. The questionnaires will be administered at baseline, prior to RP and every 3 months for 2 years post RP.
Time Frame
Up to 24 months after surgery
Title
Quality of life as assessed by EQ-5D
Description
The QOL will be measured using the EuroQol five dimensions questionnaire（EQ-5D）. The questionnaires will be administered at baseline, prior to RP and every 3 months for 2 years post RP.
Time Frame
Up to 24 months after surgery
Title
Radiographic progression-free survival (rPFS)
Description
Time from surgery to radiographic progression or death
Time Frame
2 years
Title
Overall survival
Description
Time from surgery to death due to any cause
Time Frame
5 years
Other Pre-specified Outcome Measures:
Title
Rate of Magnetic Resonance Imaging Downstaging after Neoadjuvant Therapy
Description
The rate of MRI imaging downstaging after neoadjuvant therapy
Time Frame
6 months
Title
Exploratory analysis to correlate tissue expression of PSA, CYP17, Ki67, and AR with pathologic response
Description
To correlate the expression of PSA, CYP17, Ki67, and AR by immunohistochemistry with pCR/npCR in the prostatectomy specimen.
Time Frame
6 months
10. Eligibility
Sex
Male
Gender Based
Yes
Gender Eligibility Description
Only male patient can enter this study
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age ≥ 18 years
Histologically or cytologically diagnosis of prostate cancer with positive IDC-P status
High-risk localized prostate cancer, defined by either: Tumor stage ≥T3a by digital rectal examination, or Primary tumor Gleason score ≥ 8, or PSA > 20 ng/mL
No evidence of metastases
The ECOG score of the patient is ≤2
Expected survival over 5 years
Patients must participate voluntarily and sign an informed consent form (ICF), indicating that they understand the purpose and required procedures of the study, and are willing to participate in. Patients must be willing to obey the prohibitions and restrictions specified in the research protocol
Agree to collect the tumor tissue and blood samples needed for the research and apply them to related study
Adequate hematologic, renal and hepatic function:
Absolute neutrophil count [ANC] ≥1.5 x 10^9/L
Platelet count [PLT] ≥100 x 10^9/L
Hemoglobin [HGB] ≥9 g/dL
Serum Total bilirubin [TBIL] ≤1.5 x upper limit of normal (ULN)
Aspartate aminotransferase (AST), alanine aminotransferase (ALT) < 2.5 x ULN
Serum albumin [ALB] ≥2.8 g/dL
Serum Creatinine ≤ 1.5 x ULN
Creatinine Clearance ≥ 40 mL/min
Exclusion Criteria:
Prior androgen deprivation therapy (medical or surgical), radiation therapy or chemotherapy for prostate cancer
Evidence of metastatic disease (M1) on imaging studies
Pathological finding consistent with small cell, ductal or neuroendocrine carcinoma of the prostate
Major surgery or severe trauma within 30 days before enrollment
Patients with severe or uncontrolled concurrent，including but not limited to：
Severe or uncontrolled concurrent infections
Human immunodeficiency virus [HIV] infection positive
Suffer from acute or chronic active hepatitis B (HBsAg positive and HBV DNA>1x10^3/mL) Or acute or chronic active hepatitis C (HCV antibody positive and HCV RNA>15 IU/mL)
Active tuberculosis, etc
Abnormal cardiac function as manifested by NYHA (New York Heart Association) class III or IV heart failure，or clinically significant ventricular arrhythmias
Uncontrolled hypertension（Systolic blood pressure≥160mmHg or Diastolic blood pressure≥100mmHg）
Severe or unstable angina, myocardial infarction，arterial or venous thromboembolic events (eg, pulmonary embolism, cerebrovascular accident including transient ischemic attacks) Occurred within 6 months before enrollment
Evidence of serious and/or unstable pre-existing medical, psychiatric or other condition (including laboratory abnormalities) that could interfere with patient safety or provision of informed consent to participate in this study
Any condition that in the opinion of the investigator, would preclude participation in this study
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Hao Zeng, Professor
Phone
008618980602129
Email
kucaizeng@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hao Zeng, Professor
Organizational Affiliation
West China Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
West China Hospital
City
Chengdu
State/Province
Sichuan
ZIP/Postal Code
610000
Country
China
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hao Zeng, Professor
Phone
008618980602129
Email
kucaizeng@163.com
12. IPD Sharing Statement
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Neoadjuvant Therapy of Abiraterone Plus ADT for Intraductal Carcinoma of the Prostate
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