Phase II PAP Plus GM-CSF Versus GM-CSF Alone for Non-metastatic Prostate Cancer

Randomized Phase II Trial of a DNA Vaccine Encoding Prostatic Acid Phosphatase (pTVG-HP) Versus GM-CSF Adjuvant in Patients With Non-Metastatic Prostate Cancer

The investigators are trying to find new methods to treat prostate cancer. The approach the investigators are taking is to try to enhance patients' own immune response against the cancer. In this study the investigators will be testing the effectiveness of a vaccine that may be able to help the body fight prostate cancer.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Biological: pTVG-HP; Biological: rhGM-CSF

• Study Type: Interventional
• Enrollment (Actual): 99
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94115
      • UCSF Helen Diller Family Comprehensive Cancer Center
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Johns Hopkins University/Sidney Kimmel Comprehensive Cancer Center
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Carbone Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Histologic diagnosis of adenocarcinoma of the prostate
• Completion of local therapy by surgery and/or ablative radiation therapy at least 3 months prior to entry, with removal or ablation of all visible disease, including seminal vesical and/or local lymph node involvement
• Rising prostate specific antigen (PSA) levels without scan evidence of metastatic disease
• Asymptomatic or mildly symptomatic and life expectancy of at least 4 months

Exclusion Criteria:

• Small cell or other variant prostate cancer histology
• Evidence of immunosuppression
• Prior treatment with androgen deprivation except if given neoadjuvantly or adjuvantly with radiation therapy or at time of prostatectomy. In this situation, no more than 24 months of androgen deprivation must have been given and treatment must not have been within 12 months prior to screening for this study.
• Serum testosterone at screening < 50 ng/dL
• Known bone metastases or lymph node involvement as determined by bone scan or computed tomography (CT) scan of the abdomen and pelvis within 4 weeks of study entry
• Prior vaccine therapy for prostate cancer
• Known allergic reactions to granulocyte-macrophage colony-stimulating factor (GM-CSF)
• Severe intercurrent medical conditions or laboratory abnormalities that would impart, in the judgment of the Medical Monitor, excess risk associated with study participation or study agent administration

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: pTVG-HP vaccine with GM-CSF; pTVG-HP (100 µg) with rhGM-CSF (208 µg) administered intradermally (i.d.) biweekly for 6 total doses, then every 3 months to complete a 2-year treatment period	Biological: pTVG-HP; pTVG-HP (100 µg) with rhGM-CSF (208 µg) administered intradermally (i.d.) biweekly for 6 total doses, then every 3 months to complete a 2-year treatment period
Active Comparator: GM-CSF alone; rhGM-CSF (208 µg) administered intradermally (i.d.) biweekly for 6 total doses, then every 3 months to complete a 2-year treatment period	Biological: rhGM-CSF; rhGM-CSF (208 µg) administered intradermally (i.d.) biweekly for 6 total doses, then every 3 months to complete a 2-year treatment period; Other Names: GM-CSF; granulocyte-macrophage colony-stimulating factor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
2-year Metastasis-Free Survival Rate	2-year Metastasis-Free Survival (MFS) Rate with the development of metastases by conventional imaging used to define progression (as defined by RECIST 1.1 criteria). The 2-year MFS rate estimates which were obtained using the Kaplan-Meier analysis (taking into account censoring) using the intention-to-treat population.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prostate Specific Antigen (PSA) Doubling Time (DT)	PSA DT was calculated using all serum PSA values available from the same clinical laboratory for the specified period by the equation log2/b where b denotes the least-squares estimator of the linear regression model of the log-transformed PSA values on time. Pretreatment PSA DT (3-6 months before treatment, with a minimum of 4 values), on-treatment PSA DT was determined using values from month 3 to month 9.	up to 9 months
Number and Severity of Observed Toxicities	Number of participants who experienced any adverse events greater than grade 1 that were determined to be at least possibly related to treatment, highest grade reported per participant for each adverse event (AE). All toxicities were graded using National Cancer Institute Common Terminology Criteria for Adverse Events (version 4). Higher grades indicate more severe toxicities.	2 years
Median Time to Radiographic Disease Progression	Time to metastasis was determined from the date of registration to the first CT or bone scan that demonstrated metastatic disease. As defined by RECIST 1.1 criteria.	up to 2 years
PSA Progression Free Survival		up to 2 years

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Investigators: Principal Investigator: Douglas McNeel, M.D., PhD, University of Wisconsin, Madison

Publications and helpful links

General Publications

• McNeel DG, Eickhoff JC, Johnson LE, Roth AR, Perk TG, Fong L, Antonarakis ES, Wargowski E, Jeraj R, Liu G. Phase II Trial of a DNA Vaccine Encoding Prostatic Acid Phosphatase (pTVG-HP [MVI-816]) in Patients With Progressive, Nonmetastatic, Castration-Sensitive Prostate Cancer. J Clin Oncol. 2019 Dec 20;37(36):3507-3517. doi: 10.1200/JCO.19.01701. Epub 2019 Oct 23.

Helpful Links

• University of Wisconsin Carbone Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): May 23, 2011
• Primary Completion (Actual): June 30, 2020
• Study Completion (Actual): June 30, 2020

Study Registration Dates

• First Submitted: March 24, 2011
• First Submitted That Met QC Criteria: April 22, 2011
• First Posted (Estimate): April 26, 2011

Study Record Updates

• Last Update Posted (Actual): January 20, 2021
• Last Update Submitted That Met QC Criteria: January 15, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Sargramostim; Molgramostim
• Other Study ID Numbers: CO08801; A534260 (Other Identifier: UW Madison); SMPH/MEDICINE/MEDICINE*H (Other Identifier: UW Madison); 2013-1679 (Other Identifier: Institutional Review Board); NCI-2011-00965 (Registry Identifier: NCI CTRP); Protocol Version 10/7/2015 (Other Identifier: UW Madison)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No