Prostate Cancer, Prostatic Neoplasms
Conditions
Brief summary
The purpose of this study is to determine if treatment with fulvestrant leads to a slowing of tumor progression in patients who have developed androgen-independent (AIPC) or hormone-refractory prostate cancer (HRPC) and who have a rising serum prostate specific antigen (PSA).
Detailed description
The purpose of this study is to determine if treatment with fulvestrant leads to a slowing of tumor progression in patients who have developed androgen-independent (AIPC) or hormone-refractory prostate cancer (HRPC) and who have a rising serum prostate specific antigen (PSA). In vitro studies have shown that fulvestrant downregulates androgen receptor (AR) in LNCaP cancer cell lines to a significant extent, thereby inhibiting growth of tumor cells. In addition, it is important to emphasize that fulvestrant has also been found to decrease growth of AR-negative prostate cancer cells. These observations provide the rational for using fulvestrant for the treatment of AIPC and HRPC.
Interventions
DRUGFulvestrant
Fulvestrant 250 mg IM on Days 1 and 14 in the first month, thereafter 250 mg monthly
Sponsors
AstraZeneca
Stanford University
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
* Must give signed written informed consent * Must be of age 18 years or older * Histologically confirmed adenocarcinoma of the prostate * Must be currently receiving LHRH agonists and have castrate levels of testosterone or have had an orchiectomy * Must have had rise in PSA despite anti-androgen withdrawal * Must exhibit two consecutive rises in PSA after the last hormonal manipulation * Minimum PSA \> 5mg/dL * KPS \> 80% * Up to one prior chemotherapy treatments allowed * Life expectancy of greater than 6 months
Exclusion criteria
* Concomitant hormonal therapy other than an LHRH * Noncompliance * Platelets less than 100 x 10e9 /L * International normalization ratio (INR) greater than 1.6 * Total bilirubin greater than 1.5 x ULRR * ALT or AST greater than 2.5 x ULRR if no demonstrable liver metastases or greater than 5.0 x ULRR in presence of liver metastases * History of bleeding diathesis (ie, disseminated intravascular coagulation \[DIC\], clotting factor deficiency) * History of long-term anticoagulant therapy (other than antiplatelet therapy) * History of hypersensitivity to active or inactive excipients of fulvestrant (ie, castor oil or Mannitol)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PSA Reduction ≥ 50% | 3 months | Number of subjects with serum PSA reduction ≥ 50% at 3 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PSA Doubling Time | 3 months | Number of subjects with prolongation of PSA doubling time |
| Stable Disease After One Year | 12 months | Stable disease was defined as continuing treatment without disease progression, with disease progression defined as 3 consecutive rises in serum PSA or objective progression by RECIST criteria. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Fulvestrant 250 mg IM fulvestrant (250 mg) day 1 & day 14 of 1st month, then monthly | 10 |
| Total | 10 |
Baseline characteristics
| Characteristic | Fulvestrant 250 mg |
|---|---|
| Age, Continuous | 75 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 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 | 8 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 10 |
| serious Total, serious adverse events | 3 / 10 |
Outcome results
Primary
PSA Reduction ≥ 50%
Number of subjects with serum PSA reduction ≥ 50% at 3 months
Time frame: 3 months
Population: All subjects (10 males) had castration-resistant prostate cancer. 6 had recieved prior radical prostatectomy as primary therapy. 4 had received prior chemotherapy. The majority had previously received 2 hormonal therapies. 2 had recieved radiation therapy, and 2 had recieved hormonal monotherapy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fulvestrant 250 mg | PSA Reduction ≥ 50% | 0 participants |
Secondary
PSA Doubling Time
Number of subjects with prolongation of PSA doubling time
Time frame: 3 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fulvestrant 250 mg | PSA Doubling Time | 3 participants |
Secondary
Stable Disease After One Year
Stable disease was defined as continuing treatment without disease progression, with disease progression defined as 3 consecutive rises in serum PSA or objective progression by RECIST criteria.
Time frame: 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fulvestrant 250 mg | Stable Disease After One Year | 1 participants |