A Randomized Phase I Study of Testosterone Replacement in Patients With Low Risk Hormone Refractory Prostate Cancer
- Patient has a histologically documented diagnosis of prostate adenocarcinoma (PCa)
not amenable to curative treatment with surgery or radiation treatment.
- Patient was surgically or pharmacologically castrated at least 6 months prior to
randomization. Castration must be verified by a screening testosterone value of <30
ng/dL. Any patient pharmacologically castrated must be maintained on androgen
suppression therapy for the duration of the study.
- Patient must have had a previous trial of anti-androgen therapy.
- Patients must have a documented anti-androgen withdrawal period prior to
randomization: flutamide requires a minimum 4 weeks withdrawal, and nilutamide and
bicalutamide require a minimum 6 weeks withdrawal.
- Patient must meet one of the following PSA criteria:
- A 50% rise in PSA values within a minimum rise to at least 3.0 ng/mL, within 6 months
prior to randomization, OR
- A rising PSA defined as two sequential increases in PSA values. The following data
are required: an initial value (#1) followed by a PSA value demonstrating an
increase (#2). The increase must be confirmed by another rise in PSA (#3) (3>2>1).
There must be at least 2 weeks between each qualifying PSA value and the absolute PSA
value at enrollment must be at least 3.0 ng/ml.
- At the time of screening the patient must have no evidence of visceral organ-confined
metastatic disease OR the presence of minimal bone metastases only without evidence
of visceral organ-confined metastatic disease.
- The absence of visceral organ-confined metastatic disease is defined as:
- No organ-confined soft tissue metastases (e.g. lung, liver, etc.) as verified by
chest/abdomen/pelvic CT scan.
- The presence of pathologically enlarged lymph nodes will not exclude subjects from
the study and will not be included in the definition of visceral organ-confined
- The presence of minimal bone metastases is defined as <1.4% by Bone Scan Index
criteria (see section 9).
- ECOG performance status <2 (Karnofsky >70%, see Appendix A).
- Age >18 years. Because no dosing or adverse event data are currently available on
the use of Androderm® in the context of androgen ablation in patients <18 years of
age, children are excluded from this study but will be eligible for future pediatric
phase 1 single-agent trials.
- Patients must have normal hepatic and renal function as defined below:
- total bilirubin within normal institutional limits
- AST(SGOT)/ALT(SGPT) <1.5 X institutional upper limit of normal
- Patient has had no other active malignancies with the exception of non-melanoma skin
- Patient must possess the ability to understand and be willing to sign a written
informed consent document.
- Patients with a history of any previous cytotoxic therapy or radionuclide therapy
(such as rhenium, strontium, or samarium).
- Patients may not be receiving any other investigational agents.
- Uncontrolled intercurrent illness including, but not limited to ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
- Patients with evidence of visceral organ-confined metastases other than minimal bone
metastases (as defined by <1.4% Bone Scan Index, see section 9) and/or pathologically
enlarged lymph nodes will be excluded.
- Patients with local recurrences who are candidates for local salvage therapy (e.g.
surgery, radiation, brachytherapy, cryotherapy) will be excluded.
- Patients with significant pulmonary disease who have received chronic or pulse
steroid therapy within the last 3 months prior to randomization will be excluded.
Steroid therapy for non-pulmonary, non-oncologic conditions are allowed if the
patient has been on a chronic, steady-dose regimen for a minimum of 2 months prior to
- Patients with known skin allergies to polyester, alcohol, aluminum, or silicone.