Clinical Trials /

Phase II Study of Docetaxel Before Degarelix in Patients With Newly Diagnosed Metastatic Prostate Cancer.

NCT03069937

Description:

The purpose of this study is to look at patient outcomes when docetaxel is started prior to ADT with degarelix.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase II Study of Docetaxel Before Degarelix in Patients With Newly Diagnosed Metastatic Prostate Cancer.
  • Official Title: A Phase II Study of Docetaxel Before Medical Castration With Degarelix in Patients With Newly Diagnosed Metastatic Prostatic Adenocarcinoma.

Clinical Trial IDs

  • ORG STUDY ID: 102509
  • SECONDARY ID: Pro00061532
  • NCT ID: NCT03069937

Conditions

  • Metastatic Prostatic Adenocarcinoma

Interventions

DrugSynonymsArms
DocetaxeltaxotereDocetaxel + Degarelix
DegarelixFirmagonDocetaxel + Degarelix

Purpose

The purpose of this study is to look at patient outcomes when docetaxel is started prior to ADT with degarelix.

Detailed Description

      This study will look at two drugs, docetaxel and degarelix, which are both FDA approved for
      the treatment of prostate cancer. Docetaxel is a standard chemotherapy treatment for
      metastatic prostate cancer. Degarelix is an androgen deprivation therapy (ADT) agent that
      decreases the amount of testosterone in the body, which helps to fight tumor growth. Usually,
      docetaxel is given after ADT. This study will look at how your cancer changes when docetaxel
      is started before ADT. You are being asked to participate in this study because you have
      metastatic prostate cancer that can be treated with docetaxel and ADT.
    

Trial Arms

NameTypeDescriptionInterventions
Docetaxel + DegarelixExperimentalDocetaxel (TAXOTERE) will be given for up to 6 cycles every 21 days. During the 5th and 6th cycles, degarelix (Firmagon) will be administered on Cycle 5 day 1 and cycle 6 day 8. After cycle 6, degarelix will continue to be given every 28 days for a 5 more doses, for a total of 7 doses.
  • Docetaxel
  • Degarelix

Eligibility Criteria

        INCLUSION CRITERIA Patients eligible for study participation must meet all of the following
        criteria.

          1. Histological or cytological diagnosis of adenocarcinoma of the prostate.

          2. Metastatic disease identified via radiographic assessment by CT scans of the chest,
             abdomen, pelvis, and nuclear bone scan. MRI may be used if deemed necessary by the
             investigator. See Section 8.5 for more details about radiographic assessment
             requirements.

             More specifically, patients must have at least one of the following at time of study
             enrollment:

               1. Any visceral metastases identified by CT scans or MRI.

               2. Site(s) of bony metastasis identified by nuclear bone scan, MRI, and/or CT scan.

               3. Lymph node based disease not considered to be within a single radiation therapy
                  port (e.g. at or above the aortic bifurcation.)

          3. Non-castrate testosterone level, >50 ng/dl, at study enrollment.

          4. Age greater than or equal to 18 years.

          5. ECOG performance status 0-2.

          6. Meet the following hematologic criteria within 14 days of enrollment to trial:

               1. Absolute neutrophil count > 1,500/mm3

               2. Hemoglobin > 8.0 g/dl (may be transfused)

               3. Platelet count > 100,000 mm3

          7. Have adequate end-organ function as defined by the following parameters. All lab
             values must be obtained within 14 days of enrollment to trial:

               1. Creatinine clearance of > 30 ml/min. Creatinine clearance should be determined by
                  the Cockcroft-Gault formula (Appendix A)

               2. AST < 2 x institutional ULN

               3. ALT < 2 x institutional ULN

               4. Total bilirubin < institutional ULN

          8. Agree to use barrier methods of birth control during the docetaxel portion of the
             protocol and for at least one month after last docetaxel administration.

          9. Informed and must sign and give written informed consent in accordance with
             institutional and federal guidelines.

        EXCLUSION CRITERIA

        Patients eligible for study participation CANNOT meet any of the following criteria:

          1. CNS metastases (brain or leptomeningeal).

          2. Osseous metastases felt in the opinion of the clinician to be high-risk for impending
             pathologic fracture or spinal cord compression.

          3. Active cardiac disease defined as symptomatic congestive heart failure, history of
             NYHA Class III or IV Heart Failure, uncontrollable supraventricular arrhythmias, any
             history of a ventricular arrhythmia, active angina pectoris, myocardial infarction or
             coronary intervention within 6 months of registration.

          4. Prior malignancy requiring systemic therapy within the last 5 years except for treated
             basal or squamous cell skin cancer. History of low-grade malignancies with limited
             potential to progress as determined by the primary investigator may be enrolled.

          5. Subjects must not have received any previous androgen deprivation therapy (LHRH
             agonist or LHRH antagonist) or cytotoxic therapy for prostate cancer in the metastatic
             setting.

             Exception Patients may have received no more than 30 days of anti-androgen (e.g.
             bicalutamide) in the metastatic setting prior to the start of study treatment.

          6. Subjects must not have had more than 36 months of hormonal therapy in combination with
             prostatectomy or radiation in the setting of localized disease and must not have shown
             any evidence of disease recurrence within 12 months after stopping hormonal therapy.
             Disease recurrence after hormonal therapy is defined as PSA > 0.2ng/dl after
             prostatectomy + hormonal therapy or PSA that is 2.0ng/dl more than the PSA nadir after
             radiotherapy + hormonal therapy. Previous hormonal therapy to the prostate must have
             stopped at least 12 months prior to enrollment.

          7. Subjects must not have been treated with prior docetaxel in the setting of metastatic
             prostate cancer. Subjects may have been treated with docetaxel in the setting of
             localized prostate cancer (likely as a trial-based neoadjuvant or adjuvant approach to
             prostatectomy or radiation.) Subjects treated with this approach must not have shown
             any evidence of disease recurrence within 12 months after stopping docetaxel. Disease
             recurrence after docetaxel is defined as PSA > 0.2ng/dl after prostatectomy +
             docetaxel or PSA that is 2.0ng/dl more than the PSA nadir after radiotherapy
             +docetaxel. Previous docetaxel in the setting of localized prostate cancer must have
             stopped at least 12 months prior to study enrollment.

          8. Palliative radiation therapy may have been received but not within the 30 days prior
             to study treatment.

          9. Presence of peripheral neuropathy > Grade 1.

         10. Known HIV-positive

         11. Presence of any severe or uncontrolled concurrent medical condition felt in the
             opinion of the investigator to increase the risk of serious toxicity from the study
             therapy.

         12. Prior hypersensitivity to any of the components of the study drugs.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:PSA response at 10 months
Time Frame:10 months
Safety Issue:
Description:PSA complete response is defined as PSA level less than or equal to 0.2 ng/ml for two consecutive measurements at least three weeks apart. Date of complete response will be defined as the date of first recorded value less than 0.2 ng/ml. PSA partial response is defined as a decline of PSA from trial baseline of > 50% for two consecutive measurements at least three weeks apart. Date of partial response will be defined as the date of first recorded decline of > 50% baseline. Date of partial response will be defined as the date of first recorded decline of > 50% baseline. PSA progression will be defined as > 25% increase from the PSA nadir (lowest PSA value recorded since trial enrollment) and > 2 ng/dl above the nadir. Two consecutive increases must be recorded at least three weeks apart. Date of PSA progression will be defined as the first recorded PSA value that is a > 25% increase from the PSA nadir and > 2 ng/dl above the nadir.

Secondary Outcome Measures

Measure:PSA response at 6 months
Time Frame:6 months
Safety Issue:
Description:PSA complete response is defined as PSA level less than or equal to 0.2 ng/ml for two consecutive measurements at least three weeks apart. Date of complete response will be defined as the date of first recorded value less than 0.2 ng/ml. PSA partial response is defined as a decline of PSA from trial baseline of > 50% for two consecutive measurements at least three weeks apart. Date of partial response will be defined as the date of first recorded decline of > 50% baseline. Date of partial response will be defined as the date of first recorded decline of > 50% baseline. PSA progression will be defined as > 25% increase from the PSA nadir (lowest PSA value recorded since trial enrollment) and > 2 ng/dl above the nadir. Two consecutive increases must be recorded at least three weeks apart. Date of PSA progression will be defined as the first recorded PSA value that is a > 25% increase from the PSA nadir and > 2 ng/dl above the nadir.
Measure:Frequency of adverse events (AEs) using CTCAE v. 4
Time Frame:10 months
Safety Issue:
Description:Toxicity for all evaluable patients will be defined by CTCAE (NCI Common Terminology Criteria for Adverse Events) Version 4.0.
Measure:Frequency of disease progression at 12 weeks using PSA
Time Frame:12 weeks
Safety Issue:
Description:PSA progression will be defined as > 25% increase from the PSA nadir (lowest PSA value recorded since trial enrollment) and > 2 ng/dl above the nadir. Two consecutive increases must be recorded at least two weeks apart. Date of PSA progression will be defined as the first recorded PSA value that is a > 25% increase from the PSA nadir and > 2 ng/dl above the nadir. PSA progression will not be established during the first 12 weeks of therapy (4 cycles of docetaxel) as defined by PCWG2 criteria. Thus subjects with no PSA decline from baseline during therapy will have date of PSA progression defined as first PSA value after 12 weeks that is a > 25% increase from the PSA nadir and > 2 ng/dl above the nadir.
Measure:PSA response at 12 weeks
Time Frame:12 weeks
Safety Issue:
Description:PSA complete response is defined as PSA level less than or equal to 0.2 ng/ml for two consecutive measurements at least two weeks apart. Date of complete response will be defined as the date of first recorded value less than 0.2 ng/ml. PSA Partial Response is defined as a decline of PSA from trial baseline of > 50% for two consecutive measurements at least two weeks apart. Date of partial response will be defined as the date of first recorded decline of > 50% baseline. PSA progression is defined in outcome 4.
Measure:Development of castration resistance after initiation with ADT
Time Frame:10 months
Safety Issue:
Description:This will be defined as the time from initial Degarelix injection to the time of disease progression (clinical, radiographic or PSA. Determination of castration resistant disease status will require disease progression and a measured serum testosterone level less than 50 ng/dl.
Measure:Progression free survival
Time Frame:34 months
Safety Issue:
Description:Progression free Survival (PFS) will be defined as the duration of time from start of study treatment to time of disease progression or death, whichever comes first.
Measure:Overall survival (OS)
Time Frame:34 months
Safety Issue:
Description:OS is defined as the time interval from trial enrollment to death due to any cause. Survival times will be censored for patients lost to follow-up or still alive at the trial's termination.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Medical University of South Carolina

Last Updated

May 22, 2020