Clinical trial NCT03069937: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Prostatic Adenocarcinoma
Lead sponsor: Medical University of South Carolina
Sponsor class: OTHER
Collaborators: name: Ferring Pharmaceuticals
First posted: 2017-03-03
Enrollment: 52
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Primary outcomes:
measure: PSA Response at 10 Months
timeFrame: 10 months
Secondary outcomes:
measure: PSA Response at 6 Months
timeFrame: 6 months
measure: Frequency of Adverse Events (AEs) Using CTCAE v. 4
timeFrame: 10 months
measure: Frequency of Disease Progression at 12 Weeks Using PSA
timeFrame: 12 weeks
measure: PSA Response at 12 Weeks
timeFrame: 12 weeks
measure: Development of Castration Resistance After Initiation With ADT
timeFrame: 10 months
measure: Progression Free Survival
timeFrame: 34 months
measure: Overall Survival (OS)
timeFrame: 34 months
Other outcomes:
Locations:
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
Study officials:
References: