Phase II Study of Adenovirus/PSA Vaccine in Men With Hormone - Refractory Prostate Cancer

Hormone Refractory Prostate Cancer Clinical Trial

— APP22  

Official title:

Phase II Study of Adenovirus/PSA Vaccine in Men With Hormone - Refractory Prostate Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00583024
• Other study ID #: 201705744
• Secondary ID: PC061667/2200605
• Status: Completed
• Phase: Phase 2
• Start date: December 2007
• Est. completion date: January 31, 2023

Study information

• Verified date: April 2023
• Source: University of Iowa
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: January 31, 2023
• Est. primary completion date: December 31, 2020
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 90 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hormone Refractory Prostate Cancer
• Prostatic Neoplasms

Intervention

Biological:
• ADENOVIRUS/PSA VACCINE
1x10E8 pfu in Gelfoam subcutaneously on days 0, 30, 60

Locations

Country	Name	City	State
United States	Holden Comprehensive Cancer Center	Iowa City	Iowa

Sponsors (2)

Lead Sponsor	Collaborator
David M Lubaroff	United States Department of Defense

Country where clinical trial is conducted

United States, 

References & Publications (3)

Cavacini LA, Duval M, Eder JP, Posner MR. Evidence of determinant spreading in the antibody responses to prostate cell surface antigens in patients immunized with prostate-specific antigen. Clin Cancer Res. 2002 Feb;8(2):368-73. — View Citation

Elzey BD, Siemens DR, Ratliff TL, Lubaroff DM. Immunization with type 5 adenovirus recombinant for a tumor antigen in combination with recombinant canarypox virus (ALVAC) cytokine gene delivery induces destruction of established prostate tumors. Int J Cancer. 2001 Dec 15;94(6):842-9. doi: 10.1002/ijc.1556. — View Citation

Lubaroff DM, Konety B, Link BK, Ratliff TL, Madsen T, Shannon M, Ecklund D, Williams RD. Clinical protocol: phase I study of an adenovirus/prostate-specific antigen vaccine in men with metastatic prostate cancer. Hum Gene Ther. 2006 Feb;17(2):220-9. doi: 10.1089/hum.2006.17.220. No abstract available. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	18 months
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	18 months
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)	Every 6 months, up to 14 years