Prostate Cancer
Conditions
Keywords
Prostate, Cancer, Docetaxel, 03-076
Brief summary
We postulate that multiple apoptototic events are indusce through testosterone depletion and repletion with taxotere given in conjunction with androgen withdrawal.
Interventions
DRUGGnRh (Leuprolide)
Leuprolide LUPRON
DRUGTestosterone Gel
Starting during week 3 (day 19) of cycle 1, 7.5G applied topically daily for 3 days (applied at approximately 9p)
DRUGDocetaxel
70 mg/m2 given on day o1 of each 3 week cycle
Sponsors
Memorial Sloan Kettering Cancer Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of prostate adenocarcinoma histologically confirmed at MSKCC or SKCCC. * Patient must have a serum testosterone \> 180 ng/dl. * Karnofsky performance status (KPS)\>\_70%. * Patients must have adequate organ function as defined by the following * laboratory criteria: * WBC \>\_ 3500/mm3 * ANC \>\_1500/mm3 * Platelet count \>100,000/mm3 * Hemoglobin \>8.0g/dL * Creatinine \<1.6mg/dl * Total Bilirubin WNL (unless due to Gilbert's disease and other LFTs are WNL) * SGOT and SGPT If alkaline phosphatase is \_\< 2.5 x ULN, any elevations in * AST/ALT; OR if AST/ALT is \_\<1.5 x ULN, any elevation in alkaline phos * Prior hormonal therapy is allowed as: 1. Neoadjuvant treatment prior to radiation therapy or radical pmstatectomy, provided that the total duration of therapy does not exceed 6 months (Proscar is not considered a hormone therapy). 2. One cycle of intermittent therapy up to a maximum exposure of 6 months (Proscar is not considered a hormone therapy). * Patients must be at least 18 years of age. * Patients must have signed an informed consent document stating that they understand the investigational nature of the proposed treatment
Exclusion criteria
* Clinically significant cardiac disease (New York Heart Association Class III/IV), or severe debilitating pulmonary disease. * Uncontrolled serious active infection. * Anticipated survival of less than 3 months. * Active CNS or epiduraltumor * Inability or unwillingness to comply with the treatment protocol, follow-up, or research tests * Peripheral neuropathy \>\_ grade 3. * Patients with a history of severe hypersensitivity reaction to drugs formulated with polysorbate 80. * Men of childbearing potential must be willing to consent to using effective contraception while on treatment and for at least 6 months after completion of the treatment. * Prior chemotherapy * Concomitant use of phenytoin, carbamazepine, barbiturates, rifampicin, phenobarbital, St. Johns's Wort (hypericum perforatum) and ketoconazole is prohibited.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| PSA of <_ 0.05 ng/ml After Radical Prostatectomy or Radiation Therapy and PSA <_ 2.0 ng/ml for Patients With Clinical Metastases Without Prior Definitive Therapy | Conclusion of the study (at 6 months then at 18 months post-treatment) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Effects of Testosterone Administration on Docetaxel Pharmacokinetics. | at Cycle 1 and 2 | Docetaxel Pharmacokinetic parameters for cycles 1 and 2. |
Countries
United States
Participant flow
Recruitment details
Protocol Open to Accrual: 07/08/2003 Protocol Closed to Accrual: 02/28/2006 Primary Completion Date: 02/26/2008 Recruitment Location is the Medical Clinic
Participants by arm
| Arm | Count |
|---|---|
| Lupron and Docetaxel (75mg/m2) and Testosterone for 7 Days GnRh (Leuprolide): Leuprolide LUPRON
Docetaxel: 75 mg/m2 given on day 1 of each 3 week cycle
Testosterone Gel: Starting during week 3 (day 19) of cycle 1, 7.5G applied topically daily for 7 days | 63 |
| Lupron and Docetaxel (70 mg/m2) and Testosterone for 3 Days GnRh (Leuprolide): Leuprolide LUPRON
Docetaxel: 70 mg/m2 given on day 1 of each 3 week cycle
Testosterone Gel: Starting during week 3 (day 19) of cycle 1, 7.5G applied topically daily for 3 days | 39 |
| Total | 102 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Lupron and Docetaxel (75mg/m2) and Testosterone for 7 Days | Lupron and Docetaxel (70 mg/m2) and Testosterone for 3 Days | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 20 Participants | 13 Participants | 33 Participants |
| Age, Categorical Between 18 and 65 years | 43 Participants | 26 Participants | 69 Participants |
| Age, Continuous | 65 years STANDARD_DEVIATION 25.45584412 | 58.5 years STANDARD_DEVIATION 26.1629509 | 61.5 years STANDARD_DEVIATION 30.40559159 |
| Region of Enrollment United States | 63 participants | 39 participants | 102 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 63 Participants | 39 Participants | 102 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 63 / 63 | 39 / 39 |
| serious Total, serious adverse events | 36 / 63 | 8 / 39 |
Outcome results
Primary
PSA of <_ 0.05 ng/ml After Radical Prostatectomy or Radiation Therapy and PSA <_ 2.0 ng/ml for Patients With Clinical Metastases Without Prior Definitive Therapy
Time frame: Conclusion of the study (at 6 months then at 18 months post-treatment)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lupron + Docetaxel (75mg/m2) +Testosterone (RISING PSA) | PSA of <_ 0.05 ng/ml After Radical Prostatectomy or Radiation Therapy and PSA <_ 2.0 ng/ml for Patients With Clinical Metastases Without Prior Definitive Therapy | at 6 months post-treatment | 9 participants |
| Lupron + Docetaxel (75mg/m2) +Testosterone (RISING PSA) | PSA of <_ 0.05 ng/ml After Radical Prostatectomy or Radiation Therapy and PSA <_ 2.0 ng/ml for Patients With Clinical Metastases Without Prior Definitive Therapy | at 18 months post-treatment | 0 participants |
| Lupron + Docetaxel (75mg/m2) + Testosterone for (Metastatic) | PSA of <_ 0.05 ng/ml After Radical Prostatectomy or Radiation Therapy and PSA <_ 2.0 ng/ml for Patients With Clinical Metastases Without Prior Definitive Therapy | at 18 months post-treatment | 0 participants |
| Lupron + Docetaxel (75mg/m2) + Testosterone for (Metastatic) | PSA of <_ 0.05 ng/ml After Radical Prostatectomy or Radiation Therapy and PSA <_ 2.0 ng/ml for Patients With Clinical Metastases Without Prior Definitive Therapy | at 6 months post-treatment | 14 participants |
| Lupron +Docetaxel (70 mg/m2) +Testosterone (RISING PSA) | PSA of <_ 0.05 ng/ml After Radical Prostatectomy or Radiation Therapy and PSA <_ 2.0 ng/ml for Patients With Clinical Metastases Without Prior Definitive Therapy | at 6 months post-treatment | 13 participants |
| Lupron +Docetaxel (70 mg/m2) +Testosterone (RISING PSA) | PSA of <_ 0.05 ng/ml After Radical Prostatectomy or Radiation Therapy and PSA <_ 2.0 ng/ml for Patients With Clinical Metastases Without Prior Definitive Therapy | at 18 months post-treatment | 3 participants |
| Lupron + Docetaxel (70 mg/m2) + Testosterone (Metastatic) | PSA of <_ 0.05 ng/ml After Radical Prostatectomy or Radiation Therapy and PSA <_ 2.0 ng/ml for Patients With Clinical Metastases Without Prior Definitive Therapy | at 6 months post-treatment | 12 participants |
| Lupron + Docetaxel (70 mg/m2) + Testosterone (Metastatic) | PSA of <_ 0.05 ng/ml After Radical Prostatectomy or Radiation Therapy and PSA <_ 2.0 ng/ml for Patients With Clinical Metastases Without Prior Definitive Therapy | at 18 months post-treatment | 2 participants |
Secondary
The Effects of Testosterone Administration on Docetaxel Pharmacokinetics.
Docetaxel Pharmacokinetic parameters for cycles 1 and 2.
Time frame: at Cycle 1 and 2
Population: A population pharmacokinetic model was fit to the data from all individuals simultaneously using a non-linear mixed effects modeling. This was performed using NONMEM. The NONMEM model accounts for between-patient, between-course, and residual variability (random effects) as well as parameter differences predicted by covariates (fixed effects).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lupron + Docetaxel (75mg/m2) +Testosterone (RISING PSA) | The Effects of Testosterone Administration on Docetaxel Pharmacokinetics. | Docetaxel clearance (Cycle 1) | 23.9 L/hr | Standard Deviation 12.1 |
| Lupron + Docetaxel (75mg/m2) +Testosterone (RISING PSA) | The Effects of Testosterone Administration on Docetaxel Pharmacokinetics. | Docetaxel clearance (Cycle 2) | 23.6 L/hr | Standard Deviation 7.43 |