Prostate Cancer
Conditions
Keywords
stage III prostate cancer, stage II prostate cancer, adenocarcinoma of the prostate, stage I prostate cancer, stage IV prostate cancer
Brief summary
RATIONALE: Biological therapies, such as GM-CSF, may stimulate the immune system in different ways and stop tumor cells from growing. Thalidomide may stop the growth of prostate cancer by blocking blood flow to the tumor. Giving GM-CSF and thalidomide before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. PURPOSE: This phase II trial is studying how well giving GM-CSF together with thalidomide works in treating patients undergoing surgery for high-risk prostate cancer.
Detailed description
OBJECTIVES: * Evaluate the impact of neoadjuvant sargramostim (GM-CSF) and thalidomide on pathologic response (histologic P0, margin positivity, capsular penetration), prostate-specific antigen (PSA) response, and other investigational endpoints in patients with high-risk prostate cancer undergoing prostatectomy. * Determine the safety and feasibility of GM-CSF and thalidomide. OUTLINE: This is an open-label study. Patients receive sargramostim (GM-CSF) subcutaneously on days 1, 3, and 5 and oral thalidomide on days 1-5 or 1-7 in weeks 1-4. Treatment repeats every 4 weeks for 2 courses in the absence of unacceptable toxicity. Patients undergo radical prostatectomy with bilateral pelvic lymphadenectomy at week 8 or 9. PROJECTED ACCRUAL: A total of 29 patients will be accrued for this study.
Interventions
BIOLOGICALsargramostim
administered subcutaneously, generally well tolerated doses range from 50-500 ug/m2/day
DRUGthalidomide
doses up to 400 mg/day
PROCEDUREconventional surgery
SOC care surgery
PROCEDUREneoadjuvant therapy
post radical prostatectomy
Sponsors
National Cancer Institute (NCI)
The Cleveland Clinic
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
No minimum to 120 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically confirmed adenocarcinoma of the prostate meeting any of the following criteria for high-risk disease: * Clinical stage II or III (T2b, T2c, or T3 with any grade or prostate-specific antigen \[PSA\]) * Gleason score 7 (4+3 only) or ≥ 8 (any stage or PSA) * Serum PSA ≥ 10 ng/dL (any grade or stage) * Any stage, PSA, or Gleason score with ≥ 35% chance of biochemical failure at 5 years based on Kattan's nomogram * No clinical evidence of CNS metastases * No metastatic disease as demonstrated by radiological exam (CT scan, MRI, bone scan, x-ray) within 8 weeks of study entry * Appropriate medical candidate for radical prostatectomy PATIENT CHARACTERISTICS: * ECOG performance status 0-1 * Creatinine ≤ 2.0 mg/dL * Granulocyte count ≥ 1,800/mm³ * Platelet count ≥ 100,000/mm³ * AST \< 3 times upper limit of normal * Bilirubin ≤ 1.5 mg/dL * Fertile patients must use effective contraception during and for 4 weeks after completion of study treatment * No active unresolved infection * No pre-existing peripheral neuropathy \> grade 1 * No known HIV positivity * No other malignancy within the past 5 years except curatively treated basal cell or squamous cell carcinoma of the skin or controlled Ta transitional cell carcinoma of the bladder * No known contraindication to sargramostim (GM-CSF) or thalidomide PRIOR CONCURRENT THERAPY: * No prior radiotherapy to the prostate or pelvis * No prior chemotherapy or hormonal therapy for prostate cancer * No parenteral antibiotics within the past 7 days
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients P0 at Surgery | 8 weeks | Pathologic Complete Response is defined as complete eradication of tumor. |
| Proportion of Patients With Negative Surgical Margins | 8 Weeks | Presence or Absence of prostate cancer tissue at the sites of surgical resection. This is done by reviewing the entire specimen resected at the time or Radical Prostatectomy. |
| Prostate-specific Antigen Response | 8 weeks | Number of subjects that achieved a PSA decline while on therapy. Any PSA decline while on treatment, compared with baseline PSA prior to study entry. |
| Time to Clinical Progression | 32 months | Time to progression. WIth a median follow up of 32 months (12-51 months), 5 of 26 patients developed biochemical failure. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| GM-CSF Injections and Oral Thalidomide taught to administer an injection of GM-CSF under your skin (subcutaneous injection) and will administer this medicine to yourself every Monday, Wednesday and Friday for 4 weeks at time. Thalidomide will be taken orally (by mouth) every evening at bed time. You will continue these injections 3 times a week and the daily oral medicine for up to 2 months if the therapy appears to be helping your disease.
sargramostim: administered subcutaneously, generally well tolerated doses range from 50-500 ug/m2/day
thalidomide: doses up to 400 mg/day
conventional surgery: SOC care surgery
neoadjuvant therapy: post radical prostatectomy | 27 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Physician Decision | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | GM-CSF Injections and Oral Thalidomide |
|---|---|
| Age, Continuous | 59 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 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 | 24 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 27 / 27 |
| serious Total, serious adverse events | 3 / 27 |
Outcome results
Primary
Proportion of Patients P0 at Surgery
Pathologic Complete Response is defined as complete eradication of tumor.
Time frame: 8 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GM-CSF Injections and Oral Thalidomide | Proportion of Patients P0 at Surgery | 0 Participants |
Primary
Proportion of Patients With Negative Surgical Margins
Presence or Absence of prostate cancer tissue at the sites of surgical resection. This is done by reviewing the entire specimen resected at the time or Radical Prostatectomy.
Time frame: 8 Weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GM-CSF Injections and Oral Thalidomide | Proportion of Patients With Negative Surgical Margins | 0 Participants |
Primary
Prostate-specific Antigen Response
Number of subjects that achieved a PSA decline while on therapy. Any PSA decline while on treatment, compared with baseline PSA prior to study entry.
Time frame: 8 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GM-CSF Injections and Oral Thalidomide | Prostate-specific Antigen Response | 22 Participants |
Primary
Time to Clinical Progression
Time to progression. WIth a median follow up of 32 months (12-51 months), 5 of 26 patients developed biochemical failure.
Time frame: 32 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GM-CSF Injections and Oral Thalidomide | Time to Clinical Progression | 5 Participants |