Androgen Deprivation Therapy Combined With Docetaxel for High Risk Prostate Cancer

• ClinicalTrials.gov Identifier: NCT04869371
• Recruitment Status: Active, not recruiting
• First Posted: May 3, 2021
• Last Update Posted: December 29, 2022
• Sponsor: Hongqian Guo
• Information provided by (Responsible Party): Hongqian Guo, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Study Description

Brief Summary:

This randomized, controlled, single center clinical trial aims to evaluate the efficacy and safety of Androgen Deprivation Therapy Combined with Docetaxel for High Risk Prostate Cancer with a six-month treatment cycle.

Condition or disease	Intervention/treatment	Phase
Neoadjuvant Therapy \ High Risk Prostate Cancer \ Docetaxel	Drug: Docetaxel injection; Drug: Triptorelin Pamoate for Injectable Suspension; Drug: Prednisone Acetate Tablets	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 75 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized, Controlled, Single Center Clinical Trial to Evaluate the Efficacy and Safety of Neoadjuvant Therapy With Androgen Deprivation Therapy Combined With Docetaxel for High Risk and Very High Risk Prostate Cancer
• Actual Study Start Date: December 12, 2018
• Actual Primary Completion Date: December 1, 2020
• Estimated Study Completion Date: January 1, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Androgen Deprivation Therapy with Docetaxel; All subjects in this arm will receive luteinizing hormone releasing hormone analogue (LHRHa) plus docetaxel and prednisone, as per standard of care. Triptorelin pamoate (Diphereline) 15mg will be used once per 12 weeks. Docetaxel (75 mg/m2 body surface area) will be administered as intravenous drip every 3 weeks for 6 cycles. Robot assisted radical prostatectomy will be followed in 2 weeks when 24-week treatment cycle is finished.	Drug: Docetaxel injection; 75 mg/m2 body surface area every 3 weeks for 6 cycles before robot assisted radical prostatectomy; Drug: Triptorelin Pamoate for Injectable Suspension; 15mg every 12 weeks; Drug: Prednisone Acetate Tablets; 5 mg oral low dose prednisone, once daily
Active Comparator: ADT alone; All subjects in this arm will receive LHRHa alone for 24 weeks before receiving robot assisted radical prostatectomy. Triptorelin Pamoate 15mg will be administered once per 12 weeks.	Drug: Triptorelin Pamoate for Injectable Suspension; 15mg every 12 weeks

Outcome Measures

Primary Outcome Measures :

1. Pathologic Complete Response Rate [ Time Frame: up to 8 months ]
   The proportion of subjects with no morphologically recognizable cancer cell in tumor specimens after radical prostatectomy.
2. pCR or MRD rate [ Time Frame: up to 8 months ]

   The proportion of patients with pCR or MRD. Pathologic complete response (pCR): defined as no morphologically recognizable cancer cell in tumor specimens after radical prostatectomy.

   Minimal Residual Disease (MRD): defined as residual tumors with maximum diameter of 3 mm or less after radical prostatectomy.

Secondary Outcome Measures :

1. Imaging Response Rate [ Time Frame: up to 8 months ]
   The proportion of subjects whose primary tumor is in complete remission on imaging or residual tumor's maximum diameter is less than 0.5cm.
2. Rate of Stage Degradation [ Time Frame: up to 8 months ]
   Clinical or pathological stage degradation after neoadjuvant therapy
3. Rate of Positive Surgical Margins [ Time Frame: up to 8 months ]
   The proportion of subjects with positive surgical margins after radical prostatectomy.
4. Rate of Complete Serum Remission [ Time Frame: up to 8 months ]
   The proportion of subjects whose PSA is less than or equal to 0.2 ng/ml after 6 months of treatment.
5. Operative time (min) [ Time Frame: 12 month ]
   The operative time(min) of radical prostatectomy.
6. Estimated blood loss (ml) [ Time Frame: 12 month ]
   Estimated blood loss (ml) during the process of radical prostatectomy.
7. Hospital length of stay (day) [ Time Frame: 12 month ]
   The hospitalization time, recorded in day.
8. Drainage duration (day) [ Time Frame: 12 month ]
   Length of drainage duration, recorded in day.
9. Incidence of complications (%) [ Time Frame: 12 month ]
   The proportion of subjects who suffer from major complications.
10. Recovery time of urinary continence (day) [ Time Frame: 12 month ]
    The recovery time of urinary continence (day) after radical prostatectomy, defined as 0 pad/day.
11. biochemical progression-free survival (bPFS) [ Time Frame: 3 years ]
    Biochemical progression was defined as two consecutive rising PSA values that were above 0.2ng/ml at least one month apart, or starting adjuvant therapy after surgery including radiotherapy, ADT or anti-androgen therapy. The time for bPFS was measured from randomization to biochemical progression or death from any cause.
12. metastasis-free survival (MFS) [ Time Frame: 5 years ]
    Time from date of randomization to date of evidence of systemic disease on bone scan or cross-sectional imaging.
13. Serum complete response rate [ Time Frame: after 6 month neoadjuvant therapy and before surgery ]
    Serum complete response rate, defined as the proportion of participants with PSA ≤ 0.1 ng/mL after 6-month neoadjuvant therapy.
14. Rate of extracapsular extension [ Time Frame: 12 month ]
    The proportion of patients with extracapsular extension on pathologic specimens after neoadjuvant therapy.
15. Rate of positive lymph node [ Time Frame: 12 month ]
    The proportion of patients with positive lymph node on pathologic specimens after neoadjuvant therapy.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Patients must be ≥ 18 and ≤75 years of age.
• All patients must have a histologically or cytologically diagnosis of prostate cancer and must be eligible for radical prostatectomy.

• All patients must undergo thorough tumor staging and meet one of the following criteria:

  1. multi-parameter MRI or PSMA PET / CT shows clinical staging of primary tumor ≥ T3,
  2. Gleason score of primary tumor ≥ 8, 3.prostate specific antigen (PSA) ≥20 ng/ml.
  3. Eastern Cooperative Oncology Group (ECOG) physical condition score ≤ 1.
  4. Patients must have adequate hematologic function, within 28 days prior to registration as evidenced by: white blood cell (WBC) ≥ 4.0 × 109 /L, platelets≥ 100 × 109 / L, hemoglobin ≥ 9 g / dL, and international normalized ratio (INR) < 1.5.
  5. Patients must have adequate hepatic function, within 28 days prior to registration, as evidenced by: total bilirubin (TBIL)≤1.5 x upper limit of normal (ULN),and SGOT (AST) and SGPT (ALT) ≤ 2.5 x ULN.
  6. Patients must have adequate renal function, within 28 days prior toregistration, as evidenced by serum creatinine ≤2×ULN
• 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.

Exclusion Criteria:

• Patients with prostate having neuroendocrine, small cell, or sarcoma-like features are not eligible.
• Patients with low-risk and medium-risk, localized prostate cancer (the following conditions are met at the same time) are not eligible: multiparameter MRI or PSMA PET / CT shows clinical staging of primary tumor < T3, Gleason score of primary tumor < 8, and prostate specific antigen (PSA) <20 ng/ml.
• Patients with clinical or radiological evidence of extra-regional lymph node metastases or bone metastases or visceral metastases are not eligible.
• Patients who have previously received androgen deprivation therapy (medical or surgical) or focal treatment of prostate cancer or prostate cancer radiotherapy or prostate cancer chemotherapy are not eligible.
• Patients with severe or uncontrolled concurrent infections are not eligible.
• Patients must not have New York Heart Association Class III or IV congestive heart failure at the time of screening. Patients must not have any thromboembolic event, unstable angina pectoris, myocardial infarction within 6 months prior to registration.
• Patients must not have uncontrolled severe hypertension, persistent uncontrolled diabetes, oxygen-dependent lung disease, chronic liver disease, or HIV infection.
• Patients must not have had other malignancies other than prostate cancer in the past 5 years, but cured basal cell or squamous cell skin cancers can be enrolled.
• Patients with mental illness, mental disability or inability to give informed consent are not eligible.

Contacts and Locations

Locations

China, Jiangsu

The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Nanjing, Jiangsu, China, 210000

Sponsors and Collaborators

Hongqian Guo

Investigators

• Principal Investigator: Hongqian Guo, MD; Nanjing Drum Tower Hospital, affiliated to medical school of Nanjing University

More Information

• Responsible Party: Hongqian Guo, chief physician, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
• ClinicalTrials.gov Identifier: NCT04869371
• Other Study ID Numbers: IUNU-PC-106
• First Posted: May 3, 2021
• Last Update Posted: December 29, 2022
• Last Verified: December 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Prednisone; Docetaxel; Triptorelin Pamoate; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Antineoplastic Agents, Hormonal; Luteolytic Agents; Contraceptive Agents, Female; Contraceptive Agents; Reproductive Control Agents; Contraceptive Agents, Hormonal