Metastatic Prostatic Adenocarcinoma
Conditions
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.
Interventions
DRUGDocetaxel
The docetaxel dose is a 75mg/m2 intravenous (given through the vein) injection.
DRUGDegarelix
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.
Sponsors
Ferring Pharmaceuticals
Medical University of South Carolina
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PSA Response at 10 Months | 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 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
| Measure | Time frame | Description |
|---|---|---|
| Number of Grade 3 and 4 Adverse Events Related to Docetaxel During First 4 Cycles | Up to 12 weeks (first 4 cycles of docetaxel) | This measure reports the number of Grade 3 and 4 adverse events that were possibly or probably related to docetaxel and occurred during the first 4 cycles (approximately 12 weeks) of treatment |
| Frequency of Disease Progression at 12 Weeks Using PSA | 12 weeks | 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 | 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. |
| PSA Response at 6 Months | 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 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. |
| Progression Free Survival | 34 months | 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) | From trial enrollment until death or end of follow-up (up to 52.4 months) | 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 to Development of Castration Resistance After Initiation With ADT | From initiation of Degarelix until disease progression or end of follow-up (up to 34 months) | 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. |
Countries
United States
Participant flow
Recruitment details
Of the 52 subjects in the study, 51 were evaluable for the primary endpoint. The one unevaluable subject got a second primary malignancy noted after registration but prior to start of study.
Participants by arm
| Arm | Count |
|---|---|
| Docetaxel + Degarelix 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.
Docetaxel: The docetaxel dose is a 75mg/m2 intravenous (given through the vein) injection.
Degarelix: 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. | 52 |
| Total | 52 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Second primary malignancy noted | 1 |
Baseline characteristics
| Characteristic | Docetaxel + Degarelix |
|---|---|
| Age, Continuous | 67.5 years STANDARD_DEVIATION 7.01 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 51 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 17 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 35 Participants |
| Region of Enrollment United States | 52 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 52 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 28 / 51 |
| other Total, other adverse events | 49 / 51 |
| serious Total, serious adverse events | 4 / 51 |
Outcome results
Primary
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 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
Population: The Primary endpoint for this trial is a binary indicator of PSA less than or equal to 0.2 ng/mL at 10 months (40 weeks) on study. This also represents 7 months (28 weeks) on androgen deprivation therapy with Degarelix
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Docetaxel + Degarelix | PSA Response at 10 Months | 15 Participants |
Secondary
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.
Time frame: 12 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Docetaxel + Degarelix | Frequency of Disease Progression at 12 Weeks Using PSA | 12 Participants |
Secondary
Number of Grade 3 and 4 Adverse Events Related to Docetaxel During First 4 Cycles
This measure reports the number of Grade 3 and 4 adverse events that were possibly or probably related to docetaxel and occurred during the first 4 cycles (approximately 12 weeks) of treatment
Time frame: Up to 12 weeks (first 4 cycles of docetaxel)
Population: Total possibly and probably related events that occur in the first 4 cycles Docetaxel
| Arm | Measure | Value (COUNT_OF_UNITS) |
|---|---|---|
| Docetaxel + Degarelix | Number of Grade 3 and 4 Adverse Events Related to Docetaxel During First 4 Cycles | 6 adverse events |
Secondary
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.
Time frame: From trial enrollment until death or end of follow-up (up to 52.4 months)
Population: subjects who died from any cause
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Docetaxel + Degarelix | Overall Survival (OS) | 52.4 months |
Secondary
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.
Time frame: 34 months
Population: progressions from day 1 of Docetaxel
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Docetaxel + Degarelix | Progression Free Survival | 15.9 months |
Secondary
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.
Time frame: 12 weeks
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Docetaxel + Degarelix | PSA Response at 12 Weeks | PSA complete response | 1 Participants |
| Docetaxel + Degarelix | PSA Response at 12 Weeks | PSA partial response | 20 Participants |
Secondary
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 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
Population: Undetectable PSA at 6 months is a binary indicator for each patient of PSA less than or equal to 0.2 ng/dl at 6 months (24 weeks) on study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Docetaxel + Degarelix | PSA Response at 6 Months | 14 Participants |
Secondary
Time to 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.
Time frame: From initiation of Degarelix until disease progression or end of follow-up (up to 34 months)
Population: evaluable subjects who were administered Degarelix
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Docetaxel + Degarelix | Time to Development of Castration Resistance After Initiation With ADT | 16.1 months |