Hormone Refractory Prostate Cancer
Conditions
Keywords
prostate cancer, vaccine, immunotherapy
Brief summary
This investigational study involves treatment with an Ad/PSA vaccine for men with prostate cancer who present with evidence of hormone refractory metastatic disease.
Detailed description
Subjects in this trial will be eligible if they have recent evidence of hormone refractory disease (D3) and either (a) have a positive bone scan or a positive CT scan (with obvious soft tissue metastasis or lymph nodes \>1 cm), with a PSA doubling time of \>/= 12 months, a total PSA of \< 5 mg/ml, and are asymptomatic; or (b) have a negative bone scan with any PSA doubling time, are asymptomatic, and are not a candidate for chemotherapy. This is a virus vaccine in which the gene for prostate specific antigen (PSA) has been placed into a common cold virus termed adenovirus (Ad) to produce this Ad/PSA product. The purpose of this study is to determine whether vaccination with the Ad/PSA vaccine will induce an anti-PSA immunity that will result in the destruction of the remaining prostate cancer cells. Subjects will be vaccinated three times, each injection administered at 30-day intervals. Based upon our earlier clinical trial, the vaccine is considered safe and should not induce any major side effects. The investigators hope that vaccination with this PSA virus will cause the body to produce immunity to the PSA and that immunity will destroy any cell that produces PSA. Since the only cells left in the body that produce PSA will be the cancer cells, the investigators propose that the vaccination and ensuing anti-PSA immunity will kill the prostate cancer cells. Importantly, this treatment should not cause any major side effects as would treatment with anti-cancer drugs.
Interventions
BIOLOGICALADENOVIRUS/PSA VACCINE
1x10E8 pfu in Gelfoam subcutaneously on days 0, 30, 60
Sponsors
United States Department of Defense
David M Lubaroff
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* Men with prostate cancer who present with evidence of hormone refractory disease (D3). * Men with a positive bone scan or a positive CT scan (with obvious soft tissue metastasis or lymph nodes \>1 cm), a PSA doubling time of \>/= 6 months, and a total PSA of \<10 ng/ml, and asymptomatic OR men with a negative bone scan and a negative CT scan with any PSA doubling time and asymptomatic. * Scans must be obtained within 6 weeks of initiation of treatment. * Written informed consent. * Age \>/= 18 years. * Required laboratory values (obtained within 2 weeks of initiation of treatment) * Serum creatinine \</= 2.0 mg/dL * Adequate hematologic function: granulocytes \>/= 1800 per mm3, platelets \>/= 100,000 per mm3, WBC \>/= 3700, and lymphocytes \>590. * Adequate hepatocellular function: AST \<3x upper limit of normal and total bilirubin \<1.5 mg/dl (unless bilirubin elevation is consistent with Gilbert's syndrome). * Castrate levels of testosterone of \</= 50 ng/ml. * PSA can be used as an eligibility criterion must be drawn within 28 days prior to injection number 1 and will be drawn on Day 1 for use as a baseline value.
Exclusion criteria
* Active or unresolved clinically significant infection. * Parenteral antibiotics \<7 days prior to initiation of treatment. * Evidence of prior or current CNS metastases. Specific imaging is not necessary in the absence of signs or symptoms. * Co-morbid medical conditions which would result in a life expectancy (participation) of less than 1 year. * Patients with compromised immune systems; congenital, acquired, or drug-induced (immunosuppressive agents) will be excluded from the study. Use of prednisone at doses higher than 10 mg daily (or equipotent steroid doses) for more than 7 days within 3 months of initiation of treatment is not allowed. * Pre-existing malignancies that required treatment within the past 5 years except for basal or squamous cell cancers of the skin. * Prior participation in any vaccine studies for non-infectious diseases. * Prior chemotherapy, defined as prior cytotoxic chemotherapy for prostate cancer (or any cancer unless more than 5 years have elapsed). Examples of cytotoxic chemotherapy are mitoxantrone/prednisone and taxanes. Drugs such as Casodex or ketoconazole treatment must have been completed at least 6 weeks prior to initiation of treatment. * The inability to understand the language and the clinical protocol. * Allergy or religious objection to pork products; Gelfoam is produced from pork.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Stable, Decreased, or Increased PSA Doubling Times (PSADT) | 18 months | To evaluate the increase, decrease, or stable response rates (PSA responses and changes in PSADT) of the Ad/PSA vaccine using a prime-boost immunization strategy. PSADT will be calculated based on the MSKCC online calculator. |
| Number of Participants Who Develop a Strong or Modest Anti-PSA Immune Response | 18 months | Strong or modest antibody responses to PSA measured by the binding to PSA-secreting cell lines |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Alive and Deceased Following Treatment | Every 6 months, up to 14 years | To evaluate survival in evaluable patients receiving the Ad/PSA vaccine, as measured by 2-year, 5-year, 10-year, and overall survival (OS) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Adenovirus/PSA Vaccine ADENOVIRUS/PSA VACCINE: 1x10E8 pfu in Gelfoam subcutaneously on days 0, 30, 60 | 32 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 4 |
Baseline characteristics
| Characteristic | Adenovirus/PSA Vaccine |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 26 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 31 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 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 | 32 Participants |
| Region of Enrollment United States | 32 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 21 / 32 |
| other Total, other adverse events | 18 / 32 |
| serious Total, serious adverse events | 3 / 32 |
Outcome results
Primary
Number of Participants Who Develop a Strong or Modest Anti-PSA Immune Response
Strong or modest antibody responses to PSA measured by the binding to PSA-secreting cell lines
Time frame: 18 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Adenovirus/PSA Vaccine | Number of Participants Who Develop a Strong or Modest Anti-PSA Immune Response | Strong response | 15 participants |
| Adenovirus/PSA Vaccine | Number of Participants Who Develop a Strong or Modest Anti-PSA Immune Response | Modest response | 3 participants |
Primary
Number of Participants With Stable, Decreased, or Increased PSA Doubling Times (PSADT)
To evaluate the increase, decrease, or stable response rates (PSA responses and changes in PSADT) of the Ad/PSA vaccine using a prime-boost immunization strategy. PSADT will be calculated based on the MSKCC online calculator.
Time frame: 18 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Adenovirus/PSA Vaccine | Number of Participants With Stable, Decreased, or Increased PSA Doubling Times (PSADT) | Decreased PSADT | 7 Participants |
| Adenovirus/PSA Vaccine | Number of Participants With Stable, Decreased, or Increased PSA Doubling Times (PSADT) | Stable PSADT | 2 Participants |
| Adenovirus/PSA Vaccine | Number of Participants With Stable, Decreased, or Increased PSA Doubling Times (PSADT) | Increased PSADT or PSA decline | 17 Participants |
Secondary
Number of Participants Alive and Deceased Following Treatment
To evaluate survival in evaluable patients receiving the Ad/PSA vaccine, as measured by 2-year, 5-year, 10-year, and overall survival (OS)
Time frame: Every 6 months, up to 14 years
Population: 4 patients lost to follow-up
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Adenovirus/PSA Vaccine | Number of Participants Alive and Deceased Following Treatment | 10-year survival | Deceased | 16 Participants |
| Adenovirus/PSA Vaccine | Number of Participants Alive and Deceased Following Treatment | 2-year survival | Alive | 25 Participants |
| Adenovirus/PSA Vaccine | Number of Participants Alive and Deceased Following Treatment | 2-year survival | Deceased | 3 Participants |
| Adenovirus/PSA Vaccine | Number of Participants Alive and Deceased Following Treatment | 5-year survival | Alive | 20 Participants |
| Adenovirus/PSA Vaccine | Number of Participants Alive and Deceased Following Treatment | 5-year survival | Deceased | 8 Participants |
| Adenovirus/PSA Vaccine | Number of Participants Alive and Deceased Following Treatment | 10-year survival | Alive | 12 Participants |
| Adenovirus/PSA Vaccine | Number of Participants Alive and Deceased Following Treatment | Overall survival | Alive | 7 Participants |
| Adenovirus/PSA Vaccine | Number of Participants Alive and Deceased Following Treatment | Overall survival | Deceased | 21 Participants |