Inclusion Criteria
1. Subjects must have a histological diagnosis of adenocarcinoma of the prostate which
is measurable or evaluable Stage D1 or D2
2. Age > 18
3. Subjects must have metastatic prostate cancer deemed to be unresponsive or refractory
to hormone therapy by one or more of the following (despite androgen deprivation and
antiandorgen withdrawal when applicable) check all that apply.
- Progression of bidimensionally measurable disease (see section 10.1a) assessed
within 28 days prior to registration.
- Progression of evaluable but not measurable disease (i.e., bone scan ) assessed
with 42 days prior to registration
- Rising PSA - Rising PSA is defined as at least two consecutive rises in PSA to
be documented over a reference value ( measure 1). The first rising PSA (
measure 2) must be at taken at least 7 days after the reference value. A third
confirmatory PSA measure is required (2nd beyond the reference level) to be
greater than the second measure, and it must be obtained at least 7 days after
the 2nd measure. If this is not the case, a fourth PSA is required to be taken
and be greater than the second measure. The Subject must have a PSA>= 5 ng/ml in
addition to increasing PSA to be eligible.
4. Subjects may have received prior surgery. However, at least 21 days must have elapsed
since completion of surgery and Subject must have recovered from all side effects.
5. Subjects must have stopped biophosphnates at least 28 days prior to enrollment.
Subjects should not be planning to receive concomitant bisphosphonates.
6. Subjects must have adequate hepatic function as defined by:
- a serum bilirubin <=1.5 x the institutional upper limit of normal (IULN),
- SGOT or SGPT <=2.5 x the institutional upper limit of normal obtained within 14
days prior to start of therapy
7. Subjects must have a pre-study PSA within 28 days prior to start of therapy
8. Subject may have measurable metastatic diseases by a CT scan of the abdomen and
pelvis within 28 days and by a bone scan within 42 days prior to start of therapy.
The Subject is required to have an elevated PSA >= 2 that has failed to respond to
hormone therapy.
9. Subjects must have been surgically or medically castrated. If method of castration is
LHRH agonist (leuprolide or goserelin), then the Subject should be willing to
continue the use of LHRN agonists. Castration using LHRH agonist should not be
interrupted and subjects who have stopped treatment should be willing to restart.
10. Subjects must not take vitamins, herbs, or micronutrient supplement within 28 days
prior to start of therapy.
11. Prior radiation therapy (to less than 30% of the bone marrow only) is allowed. This
includes prior use of samarium, but subjects can not have received prior strontium.
At least 28 days must have elapsed since the completion of radiation therapy and the
Subject must have recovered from side effects. Soft tissue disease which has been
radiated in the prior 2 months is not assessable as measurable disease.
12. Subjects with a history of myocardial infarction are not eligible. Subjects must have
a baseline EKG to rule out underlying cardiac disease within 42 days prior to
registration. Subjects with a history of cardiac disease, specifically CHF are
ineligible unless their disease is well-controlled. Subjects with history of CVA or
atrial fibrillation are ineligible.
13. Subjects with a history of brain metastases or who currently have treated or
untreated brain metastases are not eligible. Subjects with clinical evidence of brain
metastases must have a brain CT or MRI negative for metastatic disease within 56 days
prior to registration.
*Liver function tests should be evaluated prior to each treatment.
14. Subjects must have an ECOG performance status 0-2.
15. Subjects must have an adequate renal function as defined by:
•a serum creatinine <=1.5 x the institutional upper limit of normal obtained within 14
days prior to start of therapy and a urine protein: creatinine (UPC) ratio of <= 1.0.
16. Subjects must have the following hematological criteria (minimal values):
- Absolute neutrophil count > 1,500/mm³
- Hemoglobin of > 8.0gm/dL,
- White blood cell count >2500,
- Platelets > 100,000/mm³
17. Subjects must be able to take oral medications
EXCLUSION
1. Subjects must not have received chemotherapy, biologic therapy or any other
investigational drug for any reason within 28 days prior to start of therapy and must
have recovered from toxicities of prior therapy to grade 1 or less with the exception
of alopecia.
2. Subjects may not have ongoing problems with bowel obstruction or short bowel syndrome
characterized by grade 2 or greater diarrhea or malabsorptive disorders.
3. Men of child bearing potential must be willing to consent to using effective
contraception while on treatment and for at least 3 months thereafter.
4. Subjects with a history of severe hypersensitivity reaction to docetaxel or other
drugs formulated with polysorbate 80 will be excluded
5. Subjects should not have psychological, familial, sociological, or geographical
conditions that do not permit medical follow-up or compliance with the study
protocol.
6. Except for cancer-related abnormalities, subjects should not have unstable or
preexisting major medical conditions.
7. Subjects should not have any medical life-threatening complications of their
malignancies
8. Subjects should not have a known severe and/or uncontrolled concurrent medical
disease (e.g., uncontrolled diabetes, uncontrolled chronic renal or liver disease,
active uncontrolled infection, or HIV).
9. Subjects should not have current, recent (within 4 weeks of the first infusion of
this study), or planned participation in an experimental drug study.
10. Baseline blood pressure of < or equal to 150/100 mmHg. Subjects with a blood pressure
reading above this level should be initiated on anti-hypertensive therapy and may be
considered for protocol treatment when their blood pressure is adequately controlled.
11. Subjects with New York Heart Association (NYHA) Grade II or greater congestive heart
failure are not eligible.
12. Subjects with clinically significant peripheral vascular disease are not eligible.
13. Subjects with evidence of bleeding diathesis or coagulopathy are not eligible.
14. Subjects with central nervous system or brain metastases are not eligible.
15. Subjects who had major surgical procedure, open biopsy, or significant traumatic
injury within 28 days prior to Day 0, anticipation of need for major surgical
procedure during the course of the study are not eligible.
16. Subjects with minor surgical procedures, fine needle aspirations or core biopsies
within 7 days prior to Day 0 are not eligible.
17. Subjects with history of abdominal fistula, gastrointestinal perforation, or
intra-abdominal abscess are not eligible.
18. Subjects with serious, non-healing wound, ulcer, or bone fracture are not eligible.
19. Subjects who are diagnosed of any other malignancy except non-melanomatous skin
cancer in the past 5 years are not eligible.
20. Subjects receiving anticoagulation therapy (e.g. Coumadin) prior to registration are
not eligible. Subjects are permitted to have prior Coumadin for prophylaxis against
agents that might produce blood clots. Subjects with Aspirin are acceptable.
21. Subjects with active thrombophlebitis or hypercoagulability are not eligible.
Subjects with known history of pulmonary embolus are not eligible.
22. Subjects must have completed the baseline quality of life (QOL) measures prior to
registration: the EORTC QLQ-C30 plus the prostate cancer module; the McGill Pain
Questionnaire; the Pain Medication Log. The nurse or Clinical Research Associate must
complete the QOL cover sheet for the baseline assessment prior to registration.
Subject must be willing to complete other questionnaires while on study or they are
not eligible.
23. All Subjects must be informed and must sign and give written informed consent in
accordance with institutional and federal guidelines. Subjects who are unable to
comply with study and/or follow-up procedures are not eligible.
