Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Hormonal Therapy and Chemotherapy Followed by Prostatectomy in Patients With Prostate Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02494713
Recruitment Status : Terminated (slow enrollment; resource re-allocation)
First Posted : July 10, 2015
Results First Posted : November 27, 2018
Last Update Posted : November 27, 2018
Sponsor:
Information provided by (Responsible Party):
Robert J Amato, The University of Texas Health Science Center, Houston

Brief Summary:
This is a study for men who have locally-advanced prostate cancer and are eligible to undergo prostatectomy. Standard treatment is prostatectomy alone, but there is a chance that cancer may spread to other organs in the future, even after the prostate is removed. If this were to occur, standard treatment would be androgen deprivation therapy (ADT; hormone therapy that blocks testosterone) plus chemotherapy. Clinical trials suggest that neoadjuvant treatment (treatment given before primary therapy) may prevent a recurrence. The purpose of this research study is to assess the safety and benefit of ADT plus chemotherapy given before prostate removal.

Condition or disease Intervention/treatment Phase
Prostate Cancer Drug: Degarelix Drug: Doxorubicin Drug: Ketoconazole Drug: Docetaxel Drug: Estramustine Phase 2

Detailed Description:

This is an open-label, single-arm study of neoadjuvant ADT and chemotherapy in subjects with non-metastatic, locally-advanced prostate cancer who are eligible for radical prostatectomy.

Patients will be treated with 4 monthly injections of degarelix along with two 8-week cycles of chemotherapy. Each cycle of chemotherapy will consist of 6 weeks of chemotherapy and 2 weeks of rest. In the absence of toxicity or disease progression, patients will receive 2 cycles of treatment prior to radical prostatectomy.

The primary endpoint will be complete or near-complete pathologic response.

Safety will be assessed on any patient receiving at least one dose of study drug by the reporting of adverse events, vital signs and by the assessment of findings on physical exam and routine safety laboratory determinations. The severity of adverse events and certain abnormal laboratory findings will be assessed according to the NCI CTCAE V4.03.

Laboratory-based studies will evaluate the following:

  • Complete metabolic profile

    o BUN, creatinine, alkaline phosphatase, ALT/AST, total bilirubin, LDH, calcium, albumin, glucose, magnesium, uric acid, phosphorous

  • Electrolytes

    o Sodium, potassium, chloride, CO2 content

  • Hematology

    • CBC with differential, platelet count
    • PT, INR, PTT
  • Testosterone
  • Biomarkers

    • PSA
    • CTCs

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 4 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Neoadjuvant Androgen Deprivation Therapy and Chemotherapy Followed by Radical Prostatectomy in Patients With Prostate Cancer
Study Start Date : October 2015
Actual Primary Completion Date : September 14, 2017
Actual Study Completion Date : September 14, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arm Intervention/treatment
ADT + chemotherapy
Patients will be treated with 4 monthly injections of degarelix along with two 8-week cycles of chemotherapy (doxorubicin and ketoconazole, weeks 1, 3, 5 and docetaxel and estramustine, weeks 2, 4, 6). Each cycle of chemotherapy will consist of 6 weeks of chemotherapy and 2 weeks of rest. In the absence of toxicity or disease progression, patients will receive 2 cycles of treatment prior to radical prostatectomy.
Drug: Degarelix
Subcutaneous injection, once/month for 4 months
Other Names:
  • Firmagon
  • degarelix acetate

Drug: Doxorubicin
20 mg/m2 as a 24-hour intravenous infusion on day 1 each week, weeks 1, 3, and 5
Other Name: Adriamycin

Drug: Ketoconazole
400 mg orally 3 times daily for 7 days, in weeks 1, 3, and 5
Other Name: Nizoral

Drug: Docetaxel
35 mg/m2 intravenously on day 1 of each week, weeks 2, 4, and 6
Other Name: Taxotere

Drug: Estramustine
280 mg orally 3 times daily for 7 days, in weeks 2, 4, and 6
Other Name: Emcyt




Primary Outcome Measures :
  1. Efficacy as Measured by Pathologic Response [ Time Frame: Day of prostate removal, which is about 5 months following the day participant signed consent. ]
    Pathologic response is defined by percentage of tumor burden remaining at time of prostate removal. Percentage of tumor burden is measured based on a pathologist's assessment of the prostate tissue removed and visual estimate of how much tumor there is in the prostate.


Secondary Outcome Measures :
  1. Efficacy as Measured by Prostate-specific Antigen (PSA) Levels [ Time Frame: baseline ]
    Prostate-specific antigen, or PSA, is a protein produced by normal, as well as malignant, cells of the prostate gland. The PSA test measures the level of PSA in a man's blood. For this test, a blood sample is sent to a laboratory for analysis. The results are reported as nanograms of PSA per milliliter (ng/mL) of blood.

  2. Efficacy as Measured by Prostate-specific Antigen (PSA) Levels [ Time Frame: Cycle 2 Day 1, about 8 weeks after treatment initiation (but before prostatectomy) ]
    Prostate-specific antigen, or PSA, is a protein produced by normal, as well as malignant, cells of the prostate gland. The PSA test measures the level of PSA in a man's blood. For this test, a blood sample is sent to a laboratory for analysis. The results are reported as nanograms of PSA per milliliter (ng/mL) of blood.

  3. Efficacy as Measured by Prostate-specific Antigen (PSA) Levels [ Time Frame: Cycle 2 Day 57, about 16 weeks after treatment initiation (but before prostatectomy) ]
    Prostate-specific antigen, or PSA, is a protein produced by normal, as well as malignant, cells of the prostate gland. The PSA test measures the level of PSA in a man's blood. For this test, a blood sample is sent to a laboratory for analysis. The results are reported as nanograms of PSA per milliliter (ng/mL) of blood.

  4. Efficacy as Measured by Prostate-specific Antigen (PSA) Levels [ Time Frame: Day 133, about 19 weeks after treatment initiation (but before prostatectomy) ]
    Prostate-specific antigen, or PSA, is a protein produced by normal, as well as malignant, cells of the prostate gland. The PSA test measures the level of PSA in a man's blood. For this test, a blood sample is sent to a laboratory for analysis. The results are reported as nanograms of PSA per milliliter (ng/mL) of blood.

  5. Efficacy as Measured by Prostate-specific Antigen (PSA) Levels [ Time Frame: about 20 weeks after treatment initiation (day of prostatectomy) ]
    Prostate-specific antigen, or PSA, is a protein produced by normal, as well as malignant, cells of the prostate gland. The PSA test measures the level of PSA in a man's blood. For this test, a blood sample is sent to a laboratory for analysis. The results are reported as nanograms of PSA per milliliter (ng/mL) of blood.

  6. Efficacy as Measured by Prostate-specific Antigen (PSA) Levels [ Time Frame: about 32 weeks after treatment initiation (about 12 weeks after prostatectomy) ]
    Prostate-specific antigen, or PSA, is a protein produced by normal, as well as malignant, cells of the prostate gland. The PSA test measures the level of PSA in a man's blood. For this test, a blood sample is sent to a laboratory for analysis. The results are reported as nanograms of PSA per milliliter (ng/mL) of blood.

  7. Efficacy as Measured by Prostate-specific Antigen (PSA) Levels [ Time Frame: about 44 weeks after treatment initiation (about 24 weeks after prostatectomy) ]
    Prostate-specific antigen, or PSA, is a protein produced by normal, as well as malignant, cells of the prostate gland. The PSA test measures the level of PSA in a man's blood. For this test, a blood sample is sent to a laboratory for analysis. The results are reported as nanograms of PSA per milliliter (ng/mL) of blood.

  8. Efficacy as Measured by Prostate-specific Antigen (PSA) Levels [ Time Frame: about 68 weeks after treatment initiation (about 48 weeks after prostatectomy) ]
    Prostate-specific antigen, or PSA, is a protein produced by normal, as well as malignant, cells of the prostate gland. The PSA test measures the level of PSA in a man's blood. For this test, a blood sample is sent to a laboratory for analysis. The results are reported as nanograms of PSA per milliliter (ng/mL) of blood.

  9. Efficacy as Measured by Circulating Tumor Cell (CTC) Numbers [ Time Frame: From the time the participant signs the informed consent until prostatectomy, an average of 5 months. ]
  10. Efficacy as Measured by Volume of the Prostate Tumor as Assessed by Multiparametric Prostate Magnetic Resonance Imaging (mpMRI) [ Time Frame: baseline ]
    The volume of the prostate tumor was measured by a radiologist's assessment of multiparametric prostate magnetic resonance imaging.

  11. Efficacy as Measured by Volume of the Prostate Tumor as Assessed by Multiparametric Prostate Magnetic Resonance Imaging (mpMRI) [ Time Frame: post treatment but prior to prostatectomy (about 25 days after the end of treatment) ]
    The volume of the prostate tumor was measured by a radiologist's assessment of multiparametric prostate magnetic resonance imaging.

  12. Safety of Drug Regimen as Measured by Number of Adverse Events [ Time Frame: From the time participant first initiates ADT plus chemotherapy until participant's completion of neoadjuvant ADT plus chemotherapy. ]
    Number of adverse events was measured as a count of all participant adverse events that occurred from the time participant first initiates ADT plus chemotherapy until participant's completion of neoadjuvant ADT plus chemotherapy.

  13. Surgical Morbidity as Measured by Number of Adverse Events [ Time Frame: From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 20 months ]
    Number of adverse events was measured as a count of all participant adverse events that occurred from the time participant first initiates ADT plus chemotherapy until the participant was taken off-study or the study was stopped, an average of 20 months



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Pathologic proof of prostatic adenocarcinoma without evidence of regional and/or distant metastasis, clinical stage T1c or T2a with high grade disease (Gleason 8-10) on initial biopsy, clinical stage T2b-T2c with Gleason grade 7 (4+3), or clinical stage T3. No neuroendocrine differentiation or small cell features.
  • Recent (<6 weeks prior to study entry) negative bone scan and CT of the chest and abdomen.
  • Appropriate surgical candidate for radical prostatectomy and a performance status of <2 (ECOG scale).
  • Adequate bone marrow function as defined as an absolute peripheral granulocyte count >1500 and platelet count >100,000.
  • Adequate hepatic function per the following criteria:

    • Albumin ≥2.8 g/dL
    • AST and ALT ≤5 x ULN
    • Total bilirubin <2 mg/dL
  • Adequate renal function per the following criteria:

    o Serum creatinine ≤1.5 x ULN

  • Normal coagulation profile (INR ≤ 1.5, aPTT ≤ 1.5 x ULN for the lab) and no history of substantial non-iatrogenic bleeding diatheses. Use of anticoagulants is limited to local use only (for control of central line patency).
  • Age ≥ 18 years
  • Written informed consent to participate in this study.

Exclusion Criteria:

  • Prostatic adenocarcinoma with neuroendocrine differentiation or small cell features
  • Surgical resection or major surgery within 4 weeks or stereotactic biopsy within 1 week of first ADT and chemotherapy treatment
  • Previous or current hormonal treatment, chemotherapy, radiation therapy, immunotherapy, or investigational study drug.
  • Unable to tolerate multiparametric MRI or is contraindicated.
  • Patients not appropriate surgical candidates for radical prostatectomy based on the evaluation of coexistent medical diseases and competing causes of death.
  • Patients with uncontrolled cardiac, hepatic, renal, or neurologic/psychiatric disorder.
  • Severe gastrointestinal bleeding within 12 weeks of treatment with ADT and chemotherapy
  • Patients who are HIV positive or have chronic hepatitis B or C infections.
  • Congestive heart failure New York Heart Association (NYHA) class 3 or 4, or history of congestive heart failure New York Heart Association (NYHA) class 3 or 4, unless a 2D echocardiogram or multi-gated acquisition scan (MUGA) performed within 3 months of enrollment demonstrates a left ventricular ejection fraction >45%.
  • Sensory neuropathy grade >1.
  • History of another malignancy within the previous 5 years other than curatively treated non-melanoma skin cancer.
  • Use of herbal products that may decrease PSA levels (e.g., saw palmetto) or systemic corticosteroids greater than the equivalent of 10 mg of prednisone per day within 4 weeks of enrollment.
  • Any other condition, including concurrent medical condition, social circumstance or drug dependency, which in the opinion of the investigator could compromise patient safety and/or compliance with study requirements

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02494713


Locations
Layout table for location information
United States, Texas
UTHealth Memorial Hermann Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
The University of Texas Health Science Center, Houston
Investigators
Layout table for investigator information
Principal Investigator: Robert J Amato, D.O. The University of Texas Health Science Center, Houston
  Study Documents (Full-Text)

Documents provided by Robert J Amato, The University of Texas Health Science Center, Houston:
Layout table for additonal information
Responsible Party: Robert J Amato, Professor and Director, Division of Oncology, The University of Texas Health Science Center, Houston
ClinicalTrials.gov Identifier: NCT02494713    
Other Study ID Numbers: GU-14-101
HSC-MS-14-0424 ( Other Identifier: UTHSC-H CPHS (IRB) )
First Posted: July 10, 2015    Key Record Dates
Results First Posted: November 27, 2018
Last Update Posted: November 27, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Robert J Amato, The University of Texas Health Science Center, Houston:
Advanced Prostate Cancer
Neoadjuvant
Hormone therapy
ADT
Androgen Deprivation Therapy
Chemotherapy
Radical Prostatectomy
Additional relevant MeSH terms:
Layout table for MeSH terms
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Prostatic Diseases
Ketoconazole
Docetaxel
Doxorubicin
Estramustine
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Antifungal Agents
Anti-Infective Agents
14-alpha Demethylase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Steroid Synthesis Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Cytochrome P-450 CYP3A Inhibitors
Antineoplastic Agents, Alkylating
Alkylating Agents