Prostate Cancer
Conditions
Keywords
Prostate, Androgen, AIPC, Doxil
Brief summary
The primary objective of this study is to evaluate PSA response rates of the combination of Doxil and Thalidomide in patients with AIPC who have failed chemotherapy. Secondary objectives include: 1) To evaluate the clinical response rate of this combination on measurable disease 2) To evaluate overall survival for this combination.
Detailed description
This is an open label, Phase II trial of thalidomide and Doxil in patients with androgen independent prostate cancer whom have a rising PSA while on chemotherapy. The primary objective of this study is to evaluate PSA response rates of the combination of Doxil and Thalidomide in patients with AIPC who have failed chemotherapy. Secondary objectives include: 1) To evaluate the clinical response rate of this combination on measurable disease (If measurable soft tissue lesions are present on radiological or clinical exam) ; 2) To evaluate overall survival for this combination. There will be between 18 and 35 subjects at least 18 years of age enrolled on this single site study.
Interventions
DRUGThalidomide
100 mg PO q day and escalation will occur bt 50 mg every 4 weeks to a maximum of 200mg
DRUGDoxil
On day 1 of each cycle 40 mg/m2 IV over 1 hr every 28 days
Sponsors
Ortho Biotech, Inc.
University of Pittsburgh
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
* Histologically or cytologically confirmed adenocarcinoma of the prostate. * Confirmed androgen independent prostate cancer with evidence of rising PSA (two successive increases in PSA, at least 4 weeks apart) while on chemotherapy. If the PSA is less than 5, the increase in PSA must be at least 50%. Must also have castrate testosterone levels (\<50 ng/ml) * Patients could not have received more than 2 previous chemotherapy regimens. * No anthracyclines within the past 6 months. * No prior single agent thalidomide in the last 12 months. No prior cytotoxic chemotherapy + thalidomide given in conjunction * Age \> 18 years of age * Performance status ECOG 0-2 * Peripheral neuropathy must be \< grade 1 * Must have adequate hematologic, hepatic and renal function * Men of reproductive potential must be willing to consent to using effective contraception while on treatment and for at least 4 weeks thereafter * Patients must have left ventricular ejection fraction of \> 50% within 42 days prior to first dose of study drug. The method used at baseline must be used for later monitoring * Must have been off an anti-androgen for at least 4-6 weeks (Flutamide and Bicalutamide respectively) and documented as having a rising PSA * Measurable or evaluable disease (PSA elevation will constitute evaluable disease). Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>20 mm with conventional techniques CT scan or as \>10 mm with spiral CT scan. See section 6.B for the evaluation of measurable disease * Life expectancy of greater than 3 months * Patients must be willing and able to comply with the FDA-mandated S.T.E.P.S.® program * Ability to understand and sign written informed consent approved by the Institutional Review Board \[IRB/Ethics Committee\], which will be obtained prior to study entry.
Exclusion criteria
* Patients with unstable angina, uncompensated CHF, a history of an MI, PE or DVT within the last 3 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate | 24 weeks | The number of patients experiencing a response to treatment, per RECIST criteria / total number of patients evaluable for response. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Best Overall PSA Response | 4 weeks | PSA response as stable disease or progressive disease, per Prostate-Specific Antigen Working Group criteria. |
| Overall Survival | 36 months | — |
| Time to Progression | Up to 18 months | Time from start of treatment until the disease progression per RECIST criteria. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Thalidomide and Doxil Combination of Thalidomide and Doxil
Thalidomide: 100 mg PO q day and escalation will occur bt 50 mg every 4 weeks to a maximum of 200mg
Doxil: On day 1 of each cycle 40 mg/m2 IV over 1 hr every 28 days | 39 |
| Total | 39 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Thalidomide and Doxil |
|---|---|
| Age, Continuous | 70 years |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 39 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 39 / 39 |
| serious Total, serious adverse events | 9 / 39 |
Outcome results
Primary
Response Rate
The number of patients experiencing a response to treatment, per RECIST criteria / total number of patients evaluable for response.
Time frame: 24 weeks
Population: Patients that received greater than one cycle of therapy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Thalidomide and Doxil | Response Rate | 9.3 percentage of participants |
Secondary
Best Overall PSA Response
PSA response as stable disease or progressive disease, per Prostate-Specific Antigen Working Group criteria.
Time frame: 4 weeks
Population: Patients that received greater than one cycle of therapy and met criteria for stable or progressive disease according to Prostate-Specific Antigen Working Group criteria.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Thalidomide and Doxil | Best Overall PSA Response | Stable disease | 48.8 percentage of patients |
| Thalidomide and Doxil | Best Overall PSA Response | Progressive Disesase | 43.7 percentage of patients |
Secondary
Overall Survival
Time frame: 36 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Thalidomide and Doxil | Overall Survival | 12 months |
Secondary
Time to Progression
Time from start of treatment until the disease progression per RECIST criteria.
Time frame: Up to 18 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Thalidomide and Doxil | Time to Progression | 3.7 months |