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Pilot Trial of Chemohormonal Therapy Followed by Prostatectomy in High Risk Prostate Cancer

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ClinicalTrials.gov Identifier: NCT03358563
Recruitment Status : Recruiting
First Posted : November 30, 2017
Last Update Posted : July 31, 2019
Sponsor:
Collaborators:
United States Department of Defense
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University of Wisconsin, Madison

Tracking Information
First Submitted Date  ICMJE October 13, 2017
First Posted Date  ICMJE November 30, 2017
Last Update Posted Date July 31, 2019
Actual Study Start Date  ICMJE January 5, 2018
Estimated Primary Completion Date July 1, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 29, 2017)
Change in pCR rates [ Time Frame: Up to 6 months ]
Evaluate the pathologic complete response (pCR) rates in the primary tumor from patients with newly diagnosed locally advanced or oligometastatic prostate cancer treated with combination androgen deprivation therapy (ADT) and 3 cycles of docetaxel chemotherapy followed by prostatectomy.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03358563 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 14, 2018)
  • Change in PSA [ Time Frame: From baseline (3 months prior to prostatectomy) to 6 weeks after prostatectomy. ]
    Evaluate the percentage of change in prostate-specific antigen (PSA) from baseline (3 months prior to prostatectomy) to week 6 after prostatectomy in patients with newly diagnosed locally advanced or oligometastatic prostate cancer treated with combination ADT and docetaxel as well as the maximum decline in PSA that occurs at any point during treatment.
  • PSA Recurrence [ Time Frame: Up to 12 months ]
    Rate of patients with PSA recurrence at month 12 after surgery
  • Safety and tolerability of combination ADT and docetaxel measured by CTCAE v.4.0 [ Time Frame: Up to 6 months ]
    Evaluate safety and tolerability of the combination of ADT and docetaxel for up to three months following the last dose of docetaxel.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 29, 2017)
  • Change in PSA [ Time Frame: From baseline (3 months prior to prostatectomy) to 4 weeks after prostatectomy. ]
    Evaluate the percentage of change in prostate-specific antigen (PSA) from baseline (3 months prior to prostatectomy) to week 4 after prostatectomy in patients with newly diagnosed locally advanced or oligometastatic prostate cancer treated with combination ADT and docetaxel as well as the maximum decline in PSA that occurs at any point during treatment.
  • PSA Recurrence [ Time Frame: Up to 12 months ]
    Rate of patients with PSA recurrence at month 12 after surgery
  • Safety and tolerability of combination ADT and docetaxel measured by CTCAE v.4.0 [ Time Frame: Up to 6 months ]
    Evaluate safety and tolerability of the combination of ADT and docetaxel for up to three months following the last dose of docetaxel.
Current Other Pre-specified Outcome Measures
 (submitted: November 29, 2017)
  • Evaluating PSMA PET/MRI imaging [ Time Frame: Up to 12 months ]
    Evaluate PSMA PET/MRI imaging as a method for determining treatment response in primary prostate cancer and metastatic lesions after ADT and docetaxel.
  • Evaluating Response Heterogeneity [ Time Frame: Up to 6 months ]
    Evaluate heterogeneity of response in multifocal prostate lesions at the time the primary objective is assessed
  • Change in total tumor burden in individual lesions [ Time Frame: Up to 12 months ]
    Evaluate change in total tumor burden in individual lesions and across all lesions over time for each patient
  • Disease progression [ Time Frame: Up to 12 months ]
    Correlate disease progression on MRI, technetium Tc 99m medronate (99mTc-MDP) bone scintigraphy and CT scans with PSMA uptake measures
  • PSMA PET results and PSA response correlation [ Time Frame: Up to 12 months ]
    Correlate prostate-specific membrane antigen (PSMA) PET results with PSA response and time to PSA progression
  • Evaluate genomic signatures in multifocal prostate cancer after ADT and Docetaxel [ Time Frame: Up to 12 months ]
    Prostate cancer cells extracted from the prostatectomy specimen will undergo nucleic acid extraction. DNA will be isolated and sequenced using the Foundation Medicine Next Generation Sequencing platform or other genomic panels
  • Evaluate gene expression signatures in multifocal prostate cancer after ADT and Docetaxel [ Time Frame: Up to 12 months ]
    Prostate cancer cells will be extracted from the prostatectomy specimen and undergo nucleic acid extraction. mRNA will be isolated and analyzed with gene expression panels with quantitative RT PCR and/or next generation sequencing.
  • Evaluate gene expression signatures in prostate stroma after ADT and Docetaxel [ Time Frame: Up to 12 months ]
    Prostate stromal cells will be extracted from the prostatectomy specimen and undergo nucleic acid extraction. mRNA will be isolated and analyzed with gene expression panels with quantitative RT PCR and/or next generation sequencing.
  • Evaluate infiltrating immune cells in prostatectomy specimens after ADT and Docetaxel [ Time Frame: Up to 12 months ]
    Immune cells will be extracted from the prostatectomy specimen and bone marry biopsies. These cells are labelled with antibodies and quantified using flow cytometry.
  • Evaluating EpCAM-positive disseminated and circulating tumor cells [ Time Frame: Up to 12 months ]
    Evaluate epithelial cell adhesion molecule (EpCAM)-positive disseminated and circulating tumor cells for subcellular localization of the androgen receptor and glucocorticoid receptor
  • Disseminated and circulating tumor cell analyses versus PSMA PET/MRI and clinical outcomes [ Time Frame: Up to 12 months ]
    Correlate disseminated and circulating tumor cell analyses with the PSMA PET/MRI measures and clinical outcomes.
  • Evaluate immune microenvironment in bone marrow after ADT and Docetaxel [ Time Frame: Up to 12 months ]
    Immune cells will be extracted from the prostatectomy specimen and bone marrow biopsies.
  • Evaluate secretory profile of stroma after ADT and Docetaxel [ Time Frame: Up to 12 months ]
    Prostate stromal cells will be extracted from the prostatectomy specimen and undergo nucleic acid extraction.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Pilot Trial of Chemohormonal Therapy Followed by Prostatectomy in High Risk Prostate Cancer
Official Title  ICMJE Pilot Neoadjuvant Trial of Chemohormonal Therapy Followed by Prostatectomy in Patients With High Risk or Oligometastatic Prostate Cancer
Brief Summary This is a pilot multimodality treatment approach trial with androgen deprivation therapy in combination with docetaxel chemotherapy followed by radical prostatectomy in patients with newly diagnosed high-risk and oligometastatic prostate cancer. This study aims to evaluate the rates of complete pathologic response (pCR) at the time of prostatectomy as well as PSA response, time to PSA recurrence and safety and toxicity of the combination. This study will be heavily embedded with biomarker analyses of the tumor and tumor cells in circulation as well in the bone marrow before and after treatment and will also include imaging analyses using a novel positron emission tomography (PET) imaging technology.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Early Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Prostate Cancer
Intervention  ICMJE
  • Drug: Docetaxel
    Docetaxel is a commercially marketed product that has been approved by the FDA for the treatment of metastatic prostate cancer. It is also approved for the treatment of other malignant disease, such as locally advanced or metastatic breast cancer that returns after any prior chemotherapy; locally advanced or metastatic non-small cell lung cancer that recurs after prior platinum-based chemotherapy. However, the FDA does not currently approve its use in patients with localized prostate cancer but no evidence of radiographic metastases.
    Other Names:
    • docetaxel chemotherapy
    • taxotere
    • PR 56976
    • NSC #628503
  • Drug: Degarelix
    Degarelix is a leuteinizing hormone-releasing hormone (LHRH) antagonist. Degarelix is administered at an initial dose of 240 mg subcutaneously (2 separate injections of 120mg each totaling 240 mg) two weeks prior to cycle 1 day 's 1 treatment with chemotherapy. The initial dose is followed by a maintenance dose of 80mg administered subcutaneously as a single injection every 28 days at cycle 2 day 1 (+/- 7 days) and cycle 3 day 10 (+/- 7 days)
    Other Name: Degarelix acetate
  • Drug: Bicalutamide
    The dose for bicalutamide tablets therapy in combination with an LHRH analog (in this study, degarelix) is one 50 mg tablet once daily (morning or evening), with or without food. It is recommended that bicalutamide tablets be taken at the same time each day. Treatment with bicalutamide tablets should be started at the same time as treatment with an LHRH analog.
    Other Name: Casodex
Study Arms  ICMJE Experimental: Degarelix SC + bicalutamide + docetaxel
Degarelix SC monthly x3 + bicalutamide 50mg orally QD x 14 wks + Docetaxel 75mg/m2 IV q 21 days x 3
Interventions:
  • Drug: Docetaxel
  • Drug: Degarelix
  • Drug: Bicalutamide
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 29, 2017)
30
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 1, 2021
Estimated Primary Completion Date July 1, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Evaluate safety and tolerability of the combination of ADT and docetaxel for up to three months following the last dose of docetaxel.
  • High risk prostate cancer defined as extracapsular extension (cT3a) or seminal vesicle involvement (cT3b) or invasion of adjacent structures (cT4), serum PSA >20 ng/mL or Gleason score of 8 to 10 and/or regional lymph node or
  • Oligometastatic disease defined as disseminated metastases beyond regional lymph nodes that meet the following criteria:

    • No visceral metastases
    • Less than four bony metastases.
  • Ability to comply with all study procedures and willingness to remain supine for 120 minutes during imaging.
  • Patients must be informed of the experimental nature of the study and its potential risks, and must sign an Institutional Review Board (IRB)-approved written informed consent form indicating such an understanding.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at screening.
  • Patients must be considered candidates for prostatectomy as per standard of care.
  • Adequate hematologic and renal function as evidenced by the following within 4 weeks of day 1:

    • ANC >1500/mm3
    • Hemoglobin (HgB) >10.0 gr/dL independent of transfusion
    • Platelets >100,000/mm3
    • Creatinine <2.0 mg/dL
    • Total bilirubin < Upper Limit of Normal (ULN)
  • Estimated life expectancy of ≥ 12 months at screening.
  • Throughout the study, patient and his female partner who is of childbearing potential must use 2 acceptable methods of birth control (1 of which must include a condom as a barrier method of contraception) from screening through 3 months after last dose of study drug. Two acceptable methods of birth control thus include the following:

    • A condom (barrier method of contraception) AND One of the following is required:
    • Established and ongoing use of oral, injected, or implanted hormonal method of contraception by the female partner
    • Placement of an intrauterine device or intrauterine system by the female partner
    • Additional barrier method: Contraceptive sponge or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository by the female partner
    • Tubal ligation in the female partner performed at least 6 months before screening
    • Vasectomy or other procedure resulting in infertility (eg, bilateral orchiectomy), performed at least 6 months before screening
  • While receiving chemotherapy, the patient must use a condom if having sex with a pregnant woman.
  • Must agree not to donate sperm from first dose of study drug through 3 months after the last dose of study drug.

Exclusion Criteria:

  • Prior treatment for prostate cancer, including ADT, orchiectomy, antiandrogens, ketoconazole, abiraterone acetate or enzalutamide.
  • Prior radiation to the prostate.
  • Use of other investigational agent for prostate cancer.
  • No active secondary malignancy
  • Chronic liver disease or abnormal liver function:

    • Total bilirubin >ULN (NOTE: in subjects with Gilbert's syndrome, if total bilirubin is >ULN, measure direct and indirect bilirubin and if direct bilirubin is within normal range, subject may be eligible) or
    • Alanine (ALT) or aspartate (AST) aminotransferase >2.0 x ULN or
    • ALT or aspartate AST >1.5 x ULN concomitant with alkaline phosphatase >2.5 x ULN.
  • Peripheral neuropathy grade >1.
  • Active cardiac disease defined as active angina, symptomatic congestive heart failure, or myocardial infarction within the previous 6 months.
  • Major surgery within 4 weeks before screening.
  • Patients with known psychological or sociological conditions, addictive disorders or family problems, which would preclude compliance with the protocol.
  • Herbal supplements that have been shown to modulate testosterone or androgen signaling (e.g. Saw Palmetto) are not allowed while on study.
  • Subjects may not be enrolled concurrently on other treatment studies.
  • Any concurrent disease, infection, or comorbid condition that interferes with the ability of the patient to participate in the trial; places the patient at undue risk; or complicates the interpretation of the data, in the opinion of the investigator or medical monitor.
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Cancer Connect 800-622-8922 cancerconnect@uwcarbone.wisc.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03358563
Other Study ID Numbers  ICMJE UW17009
P30CA014520 ( U.S. NIH Grant/Contract )
2017-0606 ( Other Identifier: Institutional Review Board )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University of Wisconsin, Madison
Study Sponsor  ICMJE University of Wisconsin, Madison
Collaborators  ICMJE
  • United States Department of Defense
  • National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Christos Kyriakopoulos, MD University of Wisconsin, Madison
PRS Account University of Wisconsin, Madison
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP