Clinical Trials /

pTVG-HP and Nivolumab in Patients With Non-Metastatic PSA-Recurrent Prostate Cancer

NCT03600350

Description:

The purpose of this study is to evaluate the safety of an investigational DNA vaccine, pTVG-HP, a plasmid DNA encoding human prostatic acid phosphatase (PAP), in combination with nivolumab, and the efficacy of this combination in decreasing serum Prostate-Specific Antigen (PSA) in patients with non-metastatic, non-castrate prostate cancer (clinical stage D0/M0).

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: pTVG-HP and Nivolumab in Patients With Non-Metastatic PSA-Recurrent Prostate Cancer
  • Official Title: Phase II Trial of a DNA Vaccine Encoding Prostatic Acid Phosphatase (pTVG-HP) and Nivolumab in Patients With Non-Metastatic, PSA-Recurrent Prostate Cancer

Clinical Trial IDs

  • ORG STUDY ID: UW18008
  • SECONDARY ID: 2018-0418
  • SECONDARY ID: P30CA014520
  • NCT ID: NCT03600350

Conditions

  • Prostate Cancer

Interventions

DrugSynonymsArms
pTVG-HPTreatment Group
NivolumabOpdivoTreatment Group
GM-CSFLeukine, SargramostimTreatment Group

Purpose

The purpose of this study is to evaluate the safety of an investigational DNA vaccine, pTVG-HP, a plasmid DNA encoding human prostatic acid phosphatase (PAP), in combination with nivolumab, and the efficacy of this combination in decreasing serum Prostate-Specific Antigen (PSA) in patients with non-metastatic, non-castrate prostate cancer (clinical stage D0/M0).

Trial Arms

NameTypeDescriptionInterventions
Treatment GroupExperimentalNivolumab 240 mg IV every two weeks x 6 beginning day 1, then every four weeks x 9 beginning week 12 pTVG-HP (100 µg) administered intradermally (i.d.) every two weeks x 6 beginning day 1, then every four weeks x 9 beginning week 12 rhGM-CSF (208 µg) administered intradermally (i.d.) every two weeks x 4 beginning week 4, then every four weeks x 9 beginning week 12 NOTE: Only administered to patients for whom serum PSA obtained week 4 > serum PSA obtained at day 1.
  • pTVG-HP
  • Nivolumab
  • GM-CSF

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must be at least 18 years of age with a histologic diagnosis of
             adenocarcinoma of the prostate

          -  Patients must have undergone radical prostatectomy

          -  Patients must have completed local therapy by surgery and any adjuvant/salvage
             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.

          -  Patients must have biochemically recurrent, non-metastatic (by CT and bone scan)
             clinical stage D0/M0 disease defined by the following:

               -  Patients must have evidence of detectable serum PSA with at least 4 serum PSA
                  measurements available, from the same clinical laboratory, at least two weeks
                  apart up to one year, and the final serum PSA value must be > 2.0 ng/mL.

               -  PSA doubling time, calculated from most recent 4 serum PSA values (collected up
                  to one year prior to enrollment, at least 2 weeks apart, and all from the same
                  clinical laboratory), must be a positive number (i.e. evidence of PSA rise over
                  time).

               -  PSA doubling time will be calculated using the Memorial Sloan-Kettering Cancer
                  Center nomogram
                  (http://www.mskcc.org/applications/nomograms/prostate/PsaDoublingTime.aspx).

               -  Patients must not have definitive evidence of metastases as determined by CT of
                  the abdomen/pelvis and bone scintigraphy (bone scan). Note: patients with lesions
                  detectable by highly sensitive methods (e.g. NaF PET imaging or PSMA PET imaging)
                  will be considered eligible as long as these lesions do not meet size criteria on
                  CT imaging (visceral lesions suspicious for metastases or lymph node > 15 mm in
                  short axis) and/or are not independently observed on bone scan

          -  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, superficial bladder 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 and life expectancy of at least 12 months.

          -  Patients must have normal hematologic, renal and liver function as defined by: WBC >
             3000/mm3, hematocrit > 30%, platelet count > 100,000/mm3, serum creatinine < 1.5 mg/dl
             or a calculated creatinine clearance > 60 cc/min, AST or ALT < 3.0x ULN, 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.

          -  Willingness to provide blood samples for immune studies, per study calendar, up to one
             year after study, even if off study treatment.

        Exclusion Criteria:

          -  Small cell or other variant prostate cancer histology

          -  Patients cannot have evidence of immunosuppression or have been treated with
             immunosuppressive therapy, such as chemotherapy or chronic treatment dose
             corticosteroids (greater than the equivalent of 10 mg prednisone per day), within 3
             months of the first vaccination.

          -  Seropositive for HIV, hepatitis B (HBV) or hepatitis C (HCV) per patient history due
             to the immunosuppressive features of these diseases.

          -  Prior treatment with an LHRH agonist or nonsteroidal antiandrogen, except in the
             following circumstances: Neoadjuvant/adjuvant androgen deprivation therapy
             administered with radiation therapy or at the time of prostatectomy is acceptable,
             provided that there was no evidence of PSA progression while on treatment. In this
             situation, patients must not have received more than 24 months of androgen deprivation
             treatment. Other treatment with androgen deprivation therapy is prohibited.

          -  Serum testosterone at screening < 50 ng/dL.

          -  Patients must not be concurrently taking other medications or supplements with known
             hormonal effects, including PC-SPES, megestrol acetate, finasteride, ketoconazole,
             estradiol, or Saw Palmetto. All other medications with possible anticancer effects
             must be discussed with the PI prior to study entry.

          -  Patients previously treated with herbal supplements as described in 5.B.6 or other
             potential or experimental therapies for prostate cancer must have discontinued these
             treatments and completed at least a 4 week washout prior to beginning treatment.

          -  Patients must not have evidence of bone metastases or lymph node involvement as
             determined by bone scan or CT scan of the abdomen and pelvis within 4 weeks of study
             registration. Note: Advanced imaging modalities (such as NaF-PET/CT, choline PET/CT,
             fluciclovine, or PSMA PET scans) will NOT be used to determine evidence of metastases
             for eligibility purposes or for defining disease progression.

          -  Patients must not have been treated with a prior vaccine therapy for prostate cancer.

          -  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.

          -  Patients with unstable or severe intercurrent medical conditions or laboratory
             abnormalities that would impart, in the judgment of the PI, excess risk associated
             with study participation or study agent administration.

          -  Patients cannot have concurrent enrollment on other phase I, II, or III
             investigational therapeutic treatment studies.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of subjects within acceptable toxicity boundaries
Time Frame:up to 48 weeks
Safety Issue:
Description:Subjects will be evaluated at each visit by a review of systems based on the most recent version of the NCI common toxicity criteria. Safety and Tolerability of this intervention is defined as following: a toxicity rate p0 of at most 15% of Grade ≥ 3 toxicity events (CTCAE v.4.0) will be considered as acceptable while a toxicity rate p1=35% or more will be considered as unacceptably high. Percentage of subjects within acceptable toxicity boundaries will be reported (95% confidence intervals constructed using the Wilson score method).

Secondary Outcome Measures

Measure:Metastasis-free Survival Rate
Time Frame:Up to 2 years
Safety Issue:
Description:The 2-year metastasis-free survival will be determined by investigator review of radiographic studies (CT/MRI and bone scintigraphy) performed 2 years after study initiation in subjects who have not already met criteria for radiographic progression.
Measure:Median Radiographic Progression-free Survival
Time Frame:Up to 2 years
Safety Issue:
Description:All participants will undergo radiographic imaging prior to treatment and at 6-month intervals (or as clinically required). The appearance of lesions consistent with metastatic disease will be used to define radiographic progression.
Measure:PSA Doubling Time
Time Frame:Up to 2 years
Safety Issue:
Description:Post-treatment doubling time will be calculated from: 1) All PSA values obtained from the same clinical laboratory using the same PSA assay beginning with the PSA value at day 1 (week 0) and continuing until the end-of study (or month 24) value (PSADT 0-24). 2) All PSA values obtained from the same clinical laboratory using the same PSA assay beginning with the PSA value at day 85 (month 3) to the day 253 (month 9) value (PSADT 3-9).
Measure:PSA Response Rate (</= 50% of baseline)
Time Frame:Up to 2 years
Safety Issue:
Description:The percentage of participants with PSA values less than or equal to their baseline value after 2 year.
Measure:Number of participants requiring GM-CSF as an adjuvant after week 4
Time Frame:up to week 4
Safety Issue:
Description:GM-CSF is used as a adjuvant if the PSA at week 4 is higher than baseline.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Wisconsin, Madison

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