Back to resultsPhase II Study of Docetaxel Before Degarelix in Patients With Newly Diagnosed Metastatic Prostate Cancer.
Primary Purpose
Metastatic Prostatic Adenocarcinoma
Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Docetaxel
Degarelix
Sponsored by
About this trial
This is an interventional treatment trial for Metastatic Prostatic Adenocarcinoma
Eligibility Criteria
INCLUSION CRITERIA Patients eligible for study participation must meet all of the following criteria.
- Histological or cytological diagnosis of adenocarcinoma of the prostate.
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:
- Any visceral metastases identified by CT scans or MRI.
- Site(s) of bony metastasis identified by nuclear bone scan, MRI, and/or CT scan.
- Lymph node based disease not considered to be within a single radiation therapy port (e.g. at or above the aortic bifurcation.)
- Non-castrate testosterone level, >50 ng/dl, at study enrollment.
- Age greater than or equal to 18 years.
- ECOG performance status 0-2.
Meet the following hematologic criteria within 14 days of enrollment to trial:
- Absolute neutrophil count > 1,500/mm3
- Hemoglobin > 8.0 g/dl (may be transfused)
- Platelet count > 100,000 mm3
Have adequate end-organ function as defined by the following parameters. All lab values must be obtained within 14 days of enrollment to trial:
- Creatinine clearance of > 30 ml/min. Creatinine clearance should be determined by the Cockcroft-Gault formula (Appendix A)
- AST < 2 x institutional ULN
- ALT < 2 x institutional ULN
- Total bilirubin < institutional ULN
- 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.
- 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:
- CNS metastases (brain or leptomeningeal).
- Osseous metastases felt in the opinion of the clinician to be high-risk for impending pathologic fracture or spinal cord compression.
- 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.
- 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.
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.
- 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.
- 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.
- Palliative radiation therapy may have been received but not within the 30 days prior to study treatment.
- Presence of peripheral neuropathy > Grade 1.
- Known HIV-positive
- 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.
- Prior hypersensitivity to any of the components of the study drugs.
Sites / Locations
- Medical University of South Carolina
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Docetaxel + Degarelix
Arm Description
Docetaxel (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.
Outcomes
Primary Outcome Measures
PSA response at 10 months
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
PSA response at 6 months
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.
Frequency of adverse events (AEs) using CTCAE v. 4
Toxicity for all evaluable patients will be defined by CTCAE (NCI Common Terminology Criteria for Adverse Events) Version 4.0.
Frequency of disease progression at 12 weeks using PSA
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.
PSA response at 12 weeks
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.
Development of castration resistance after initiation with ADT
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.
Progression free survival
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.
Overall survival (OS)
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.
Full Information
NCT ID
NCT03069937
First Posted
February 28, 2017
Last Updated
July 1, 2023
Sponsor
Medical University of South Carolina
Collaborators
Ferring Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT03069937
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.
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
March 1, 2017 (Actual)
Primary Completion Date
September 30, 2023 (Anticipated)
Study Completion Date
December 31, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Medical University of South Carolina
Collaborators
Ferring Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Prostatic Adenocarcinoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
52 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Docetaxel + Degarelix
Arm Type
Experimental
Arm Description
Docetaxel (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.
Intervention Type
Drug
Intervention Name(s)
Docetaxel
Other Intervention Name(s)
taxotere
Intervention Description
The docetaxel dose is a 75mg/m2 intravenous (given through the vein) injection.
Intervention Type
Drug
Intervention Name(s)
Degarelix
Other Intervention Name(s)
Firmagon
Intervention Description
Degarelix will be given as a subcutaneous (given under the skin) injection in the abdomen. The first dose will be a 240mg dose; all other doses will be 80 mg.
Primary Outcome Measure Information:
Title
PSA response at 10 months
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.
Time Frame
10 months
Secondary Outcome Measure Information:
Title
PSA response at 6 months
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.
Time Frame
6 months
Title
Frequency of adverse events (AEs) using CTCAE v. 4
Description
Toxicity for all evaluable patients will be defined by CTCAE (NCI Common Terminology Criteria for Adverse Events) Version 4.0.
Time Frame
10 months
Title
Frequency of disease progression at 12 weeks using PSA
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.
Time Frame
12 weeks
Title
PSA response at 12 weeks
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.
Time Frame
12 weeks
Title
Development of castration resistance after initiation with ADT
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.
Time Frame
10 months
Title
Progression free survival
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.
Time Frame
34 months
Title
Overall survival (OS)
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.
Time Frame
34 months
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
INCLUSION CRITERIA Patients eligible for study participation must meet all of the following criteria.
Histological or cytological diagnosis of adenocarcinoma of the prostate.
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:
Any visceral metastases identified by CT scans or MRI.
Site(s) of bony metastasis identified by nuclear bone scan, MRI, and/or CT scan.
Lymph node based disease not considered to be within a single radiation therapy port (e.g. at or above the aortic bifurcation.)
Non-castrate testosterone level, >50 ng/dl, at study enrollment.
Age greater than or equal to 18 years.
ECOG performance status 0-2.
Meet the following hematologic criteria within 14 days of enrollment to trial:
Absolute neutrophil count > 1,500/mm3
Hemoglobin > 8.0 g/dl (may be transfused)
Platelet count > 100,000 mm3
Have adequate end-organ function as defined by the following parameters. All lab values must be obtained within 14 days of enrollment to trial:
Creatinine clearance of > 30 ml/min. Creatinine clearance should be determined by the Cockcroft-Gault formula (Appendix A)
AST < 2 x institutional ULN
ALT < 2 x institutional ULN
Total bilirubin < institutional ULN
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.
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:
CNS metastases (brain or leptomeningeal).
Osseous metastases felt in the opinion of the clinician to be high-risk for impending pathologic fracture or spinal cord compression.
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.
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.
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.
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.
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.
Palliative radiation therapy may have been received but not within the 30 days prior to study treatment.
Presence of peripheral neuropathy > Grade 1.
Known HIV-positive
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.
Prior hypersensitivity to any of the components of the study drugs.
Facility Information:
Facility Name
Medical University of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Phase II Study of Docetaxel Before Degarelix in Patients With Newly Diagnosed Metastatic Prostate Cancer.
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