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A Phase I Study of a DNA Vaccine Encoding Androgen Receptor Ligand-Binding Domain (AR LBD) +/-GMCSF

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ClinicalTrials.gov Identifier: NCT02411786
Recruitment Status : Active, not recruiting
First Posted : April 8, 2015
Last Update Posted : November 14, 2018
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Madison Vaccines Incorporated
Information provided by (Responsible Party):
University of Wisconsin, Madison

Brief Summary:
The purpose of this study is to determine if a vaccine called pTVG-AR can enhance patients' immune response against prostate cancer.

Condition or disease Intervention/treatment Phase
Prostate Cancer Biological: pTVG-AR Biological: gm-csf Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Study of a DNA Vaccine Encoding Androgen Receptor Ligand-Binding Domain (AR LBD), With or Without Granulocyte Macrophage Colony-Stimulating Factor Adjuvant, in Patients With Metastatic Prostate Cancer
Actual Study Start Date : July 27, 2015
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arm Intervention/treatment
Experimental: pTVG-AR biweekly
pTVG-AR (dose: 100 µg) alone without rhGM-CSF. Administered at weeks 0, 2, 4, 6, 8, and 10 (biweekly) for 6 doses, then administered at week 12, week 24, week 36, and week 48 (quarterly) for 4 doses, or 10 total doses.
Biological: pTVG-AR
Given ID
Other Name: pTVG-AR vaccine

Experimental: pTVG-AR staggered biweekly
pTVG-AR (dose: 100 µg) alone without rhGM-CSF. Administered at weeks 0, 2, 12, 14, 24, 26, 36, 38, 48 and 50 (staggered biweekly schedule) for 10 total doses.
Biological: pTVG-AR
Given ID
Other Name: pTVG-AR vaccine

Experimental: pTVG-AR with rhGM-CSF biweekly
pTVG-AR (dose: 100 µg) with rhGM-CSF (200 µg). Administered at weeks 0, 2, 4, 6, 8, and 10 (biweekly) for 6 doses, then administered at week 12, week 24, week 36, and week 48 (quarterly) for 4 doses, or 10 total doses.
Biological: pTVG-AR
Given ID
Other Name: pTVG-AR vaccine

Biological: gm-csf
Given ID
Other Names:
  • Recombinant human GM-CSF
  • rhGM-CSF

Experimental: pTVG-AR with rhGM-CSF staggered biweekly
pTVG-AR (dose: 100 µg) with rhGM-CSF (200 µg). Administered at weeks 0, 2, 12, 14, 24, 26, 36, 38, 48 and 50 (staggered biweekly schedule) for 10 total doses.
Biological: pTVG-AR
Given ID
Other Name: pTVG-AR vaccine

Biological: gm-csf
Given ID
Other Names:
  • Recombinant human GM-CSF
  • rhGM-CSF




Primary Outcome Measures :
  1. Number and severity of adverse events following serial intradermal vaccinations of a DNA vaccine encoding AR LBD, with or without GM-CSF as an adjuvant, in patients with metastatic prostate cancer [ Time Frame: From first immunization to Week 72 ]
  2. Immune Response Rate [ Time Frame: From first immunization to Week 72 ]

Secondary Outcome Measures :
  1. Median Progression-Free Survival [ Time Frame: From first immunization to Week 72 ]
    Median time to PSA progression will be determined as a function of the date the patient started on androgen deprivation and as a function of treatment start date (week 0). Development of new metastases or discontinuation of study to begin other therapy, while not expected to precede a PSA progression endpoint, would also constitute a progression endpoint.

  2. 18-Month Progression-Free Survival [ Time Frame: 18 months ]
  3. The proportion of patients with a T-cell immune response. [ Time Frame: From first immunization to Week 72 ]
    Generation of AR LBD-specific peptide-specific CD8+ T cells as defined by ELISPOT and tetramer staining

  4. The number of patients that generate antigen specific tolerance [ Time Frame: From first immunization to Week 72 ]
    Antigen-specific tolerance generation following multiple immunizations

  5. Association between pre-existing immune responses to the AR LBD and development of subsequent effector and memory T-cell immune response [ Time Frame: From first immunization to Week 72 ]
  6. Association between development of antigen-specific T cells and 18-month progression-free survival [ Time Frame: From first immunization to Week 72 ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must be at least 18 years of age with a histologic diagnosis of adenocarcinoma of the prostate.
  • Patients must have metastatic prostate cancer (clinical stage D1 or D2 disease), with previously documented lymph node, soft tissue and/or bone metastases by radiographic imaging (including CT (or MRI) of abdomen and pelvis and bone scintigraphy). Patients in situations in which there is a reasonable clinical suspicion of a second primary tumor (or other non-prostate cancer reason for radiographic abnormalities) are not eligible unless metastatic disease is histologically confirmed to be prostate cancer.
  • Patients must have started androgen deprivation therapy (bilateral orchiectomy versus LHRH agonist, and with or without androgen antagonist) at least one month (4 weeks) prior to enrollment and no more than six months (24 weeks) prior to enrollment. Patients must continue the androgen deprivation therapy throughout the study period, and patients are not permitted to change the type of androgen deprivation therapy (e.g. by adding an androgen antagonist) during the course of investigational therapy.
  • Patients must have a serum testosterone < 50 ng/dL demonstrated within 1 month of study entry.
  • Patients must either not be a candidate for docetaxel chemotherapy for newly diagnosed metastatic prostate cancer, as determined by their treating oncologist, or have declined this therapy
  • Patients must have evidence of response to androgen deprivation as defined by a documented decline in serum PSA values from pre-androgen deprivation treatment baseline and without evidence of PSA progression while on androgen deprivation (defined by PCWG2 criteria as a 25% increase in serum PSA and an absolute increase of 2 ng/mL over nadir).
  • Patients with a prior history of a second malignancy are eligible provided they have been treated with curative intent and have been free of disease greater than three years. There will be no exclusion for patients with a history of basal cell carcinoma, squamous cell skin cancer, or other in situ carcinoma that has been adequately treated.
  • Patients who are sexually active must use a reliable form of contraception while on study and for 4 weeks after the last immunization.
  • ECOG performance score < 2.
  • Patients must have adequate hematologic, renal and liver function as defined by: WBC > 3000/mm3, hematocrit > 30%, platelet count > 100,000/mm3, serum creatinine < 1.6 mg/dl or a calculated creatinine clearance > 60 cc/min, and serum bilirubin < 2.0 mg/dl, within 4 weeks prior to first immunization.
  • Patients must be informed of the experimental nature of the study and its potential risks and must sign an IRB-approved written informed consent form indicating such an understanding.

Exclusion Criteria:

  • Small cell or other (non-adenocarcinoma) variant prostate cancer histology.
  • Patients cannot have evidence of immunosuppression or have been treated with immunosuppressive therapy, such as chemotherapy, chronic treatment dose corticosteroids (greater than the equivalent of 10 mg prednisone per day), or radiation therapy to >30% of the bone marrow, within 6 months of the first vaccination. Treatment or salvage radiation therapy encompassing < 30% of bone marrow must have been completed 4 weeks prior to the first vaccination.
  • Seropositive for HIV, hepatitis B (HBV) or hepatitis C (HCV) per patient history.
  • Patients previously treated with neoadjuvant and/or adjuvant androgen deprivation (e.g. with radiation therapy) prior to the 6-month eligibility period are allowed, assuming they did not meet criteria for progression (defined by PCWG2 criteria as a 25% increase in serum PSA and an absolute increase of 2 ng/mL over nadir) while on treatment.
  • Patients must not be concurrently taking other medications or supplements with known hormonal effects (other than LHRH agonists or non-steroidal anti-androgen), including PC-SPES, megestrol acetate, finasteride, ketoconazole, estradiol, or Saw Palmetto. All other medications with possible anti-cancer effects must be discussed with the Protocol Principal Investigator prior to study entry.
  • Patients previously treated with herbal supplements as described in 6.B.5, or other potential or experimental therapies for prostate cancer (apart from LHRH agonists and antiandrogens as described in 6.A.3 above), must have been discontinued these treatments and completed at least a one-month washout prior to first vaccination.
  • Patients must not have plans to receive concomitant chemotherapy, other biological or immune therapies, or radiation therapy for the treatment of prostate cancer during the period of study treatment.
  • Patients must not have known psychological or sociological conditions, addictive disorders or family problems, which would preclude compliance with the protocol.
  • Patients must not have known allergic reactions to GM-CSF or the tetanus vaccine.
  • Prior treatment with another experimental anti-tumor vaccine is permissible.
  • Patients with unstable or severe intercurrent medical conditions or laboratory abnormalities that would impart, in the judgment of the Protocol Principal Investigator, excess risk associated with study participation or study agent administration.
  • Unable or unwilling to undergo two leukapheresis procedures.
  • Patients with medical conditions precluding leukapheresis.
  • Patients cannot have concurrent enrollment on other phase I, II, or III investigational treatment studies for the treatment of prostate cancer.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02411786


Locations
United States, New Jersey
Cancer Institute of New Jersey
New Brunswick, New Jersey, United States, 08903
United States, Washington
University of Washington Seattle Cancer Care Alliance
Seattle, Washington, United States, 98109
United States, Wisconsin
University of Wisconsin Carbone Cancer Center
Madison, Wisconsin, United States, 53792
Sponsors and Collaborators
University of Wisconsin, Madison
National Cancer Institute (NCI)
Madison Vaccines Incorporated
Investigators
Principal Investigator: Douglas G. McNeel, M.D., Ph.D. UW Carbone Cancer Center

Responsible Party: University of Wisconsin, Madison
ClinicalTrials.gov Identifier: NCT02411786     History of Changes
Other Study ID Numbers: UW14072
5P30CA014520-40 ( U.S. NIH Grant/Contract )
First Posted: April 8, 2015    Key Record Dates
Last Update Posted: November 14, 2018
Last Verified: November 2018

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Vaccines
Androgens
Molgramostim
Immunologic Factors
Physiological Effects of Drugs
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents