pTVG-HP DNA Vaccine With or Without pTVG-AR DNA Vaccine and Pembrolizumab in Patients With Castration-Resistant, Metastatic Prostate Cancer

Running, not enrolling · Phase 2

Conditions studied: Castration-resistant Prostate Cancer, Metastatic Cancer, Prostate Cancer

In brief

This trial will evaluate the use of one versus two DNA vaccines, delivered concurrently with PD-1 blockade using pembrolizumab followed by treatment with pembrolizumab alone, and delivered over a prolonged period of time (for a maximum of 2 years (32 cycles) or until radiographic progression) on the treatment of castrate-resistant, metastatic prostate cancer. The hypothesis to be tested is that delivering two vaccines with PD-1 blockade will elicit a greater frequency and magnitude of tumor-directed CD8+ T cells, and thereby increase the percentage of patients experiencing objective anti-tumor effect as measured by PSA declines and/or objective radiographic responses. Participants must be 18 years of age or older and can expect to be on treatment for 2 years (32 cycles) and on study for up to 7 years (including 5 years of follow up via phone).

Key facts

Study ID

NCT04090528

Run by

University of Wisconsin, Madison

People needed

60

Starts

2019-10-21

Expected to finish

2027-03-01

Last updated by the study team

2026-06-25

Who can join

Age: 18 and older. Sex: male. Healthy volunteers: not accepted.

You may qualify if…

• Histologically confirmed diagnosis of prostate cancer (adenocarcinoma of the prostate)
• Metastatic disease as evidenced by the presence of soft tissue and/or bone metastases on imaging studies (CT of abdomen/pelvis, bone scintigraphy)
• Castrate-resistant disease, defined as follows:
• All participants must have received (and be receiving) standard of care androgen deprivation treatment (surgical castration versus GnRH analogue or antagonist treatment); subjects receiving Gonadotropin-releasing hormone (GnRH) analogue or antagonist must continue this treatment throughout the time on this study.
• Participants may or may not have been treated previously with a nonsteroidal antiandrogen. For participants previously treated with an antiandrogen, they must be off use of anti-androgen for at least 28 days before day 1 (for flutamide, apalutamide, enzalutamide, or other 2nd generation AR antagonists) or 6 weeks (for bicalutamide or nilutamide) prior to registration. Moreover, participants who demonstrate an anti-androgen withdrawal response, defined as a > 25% decline in PSA within 4-6 week of stopping a nonsteroidal antiandrogen, are not eligible until the PSA rises above the nadir observed after antiandrogen withdrawal.
• Participants must have a castrate serum level of testosterone (< 50 ng/dL) within 6 weeks of day 1
• Progressive disease while receiving androgen deprivation therapy defined by any one of the following as per the Prostate Cancer Clinical Trials Working Group 3 (PCWG3) bone scan criteria or RECIST 1.1 during or after completing last therapy:
• PSA: At least two consecutive rises in serum PSA, obtained at a minimum of 1-week intervals, with the final value > 2.0 ng/mL.
• Measurable disease: > 50% increase in the sum of the cross products of all measurable lesions or the development of new measurable lesions. The short axis of a target lymph node must be at least 15 mm by spiral CT to be considered a target lesion
• Non-measurable (bone) disease: The appearance of two or more new areas of uptake on bone scan (or Sodium Fluoride (NaF) positron emission tomography-computed tomography (PET/CT)) consistent with metastatic disease compared to previous imaging during castration therapy. The increased uptake of pre-existing lesions on bone scan will not be taken to constitute progression, and ambiguous results must be confirmed by other imaging modalities (e.g. X-ray, CT or MRI).
• Prior treatment with abiraterone or enzalutamide is permitted, but participants must have weaned to a daily corticosteroid dose equivalent of no more than 5 mg prednisone daily for at least 28 days prior to day 1.
• Life expectancy of at least 6 months
• Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
• Adequate hematologic, renal, liver, and coagulation function as evidenced by the following within 6 weeks of day 1:
• White Blood Cells (WBC) >/= 2000 / mm3
• Absolute Neutrophil Count (ANC) >/= 1500 / mm3
• Hemoglobin (HgB) >/= 9.0 gm/dL (Participants must not have received a blood transfusion within 14 days)
• Platelets >/= 100,000 / mm3
• Creatinine </= 1.5 x institutional upper limit of normal (ULN)
• Total bilirubin </= 1.5 x institutional ULN OR direct bilirubin </= ULN for participants with total bilirubin levels > 1.5 x ULN
• Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) </= 2.5 x institutional upper limit of normal
• Prothrombin Time (PT) or International Normalized Ratio (INR) </= 1.5 x ULN unless participant is receiving anticoagulant therapy and PT is within therapeutic range of intended use of anticoagulant (only required for participants receiving biopsy)
• Partial Thromboplastin Time (PTT) </= 1.5 x ULN unless participant is receiving anticoagulant therapy and a PTT is within therapeutic range of intended use of anticoagulant (only required for participants receiving biopsy)
• No known history of human immunodeficiency viruses (HIV 1 and 2), Human T-cell leukemia virus type 1 (HTLV-1), or active Hepatitis B or Hepatitis C
• Participants must be at least 4 weeks from any prior treatments and have recovered (to < Grade 2) from acute toxicity attributed to this prior treatment, unless considered chronic

You may not qualify if…

• Small cell or other variant (non-adenocarcinoma) prostate cancer histology, unless there is evidence that the tumor expresses PAP
• Participants may not be receiving other investigational agents or be receiving concurrent anticancer therapy other than standard androgen deprivation therapy
• Concurrent bisphosphonate therapy is not excluded, however participants should not start bisphosphonate therapy while on this study; those participants already receiving bisphosphonate therapy should continue at the same dosing and schedule as prior to study entry
• Rapidly progressive symptomatic metastatic disease, as defined by the need for increased opioid analgesics within one month of registration for the treatment of pain attributed to a prostate cancer metastatic lesion; participants receiving opioids must receive approval from the PI for eligibility
• Treatment with any of the following medications within 28 days of day 1, or while on study, is prohibited:
• Systemic corticosteroids (at doses over the equivalent of 5 mg prednisone daily); inhaled, intranasal or topical corticosteroids are acceptable
• Prostate Cancer and spes (PC-SPES)
• Megestrol
• Ketoconazole
• 5-α-reductase inhibitors - participants already taking 5-α-reductase inhibitors prior to 28 days prior to registration may stay on these agents throughout the course of therapy, but these should not be started while participants are on study
• Diethyl stilbesterol
• Abiraterone
• Enzalutamide
• Apalutamide
• Radium 223 (Xofigo®)
• Any other hormonal agent or supplement being used with the intent of cancer treatment must be reviewed by the PI for eligibility
• External beam radiation therapy within 4 weeks of registration is prohibited, or anticipated need for radiation therapy (e.g. imminent pathological fracture or spinal cord compression) within 3 months of registration. Participants must have recovered from all radiation-related toxicities and not have had radiation pneumonitis.
• Major surgery within 4 weeks of registration is prohibited
• Prior cytotoxic chemotherapy (for example, but not limited to, docetaxel, mitoxantrone, cabazitaxel) within 28 days of registration is prohibited
• Prior treatment with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or with any agent directed to another T-cell stimulatory or inhibitory receptor (e.g. CTLA-4, OX-40, CD137).
• Participants with a history of life-threatening autoimmune disease
• Participants with a history of non-infectious pneumonitis that required corticosteroid treatment, or has current pneumonitis
• Participants with a history of allergic reactions to the tetanus vaccine
• Participants who have undergone splenectomy or who have a diagnosis of immunodeficiency
• Participants must not have other active malignancies other than non-melanoma skin cancers or superficial (non-muscle-invasive) carcinoma of the bladder. Participants with a history of other cancers who have been adequately treated and have been recurrence-free for > 3 years are eligible.

Where it is running

• Washington University Siteman Cancer Center — St Louis, Missouri, United States
• University of Wisconsin Carbone Cancer Center — Madison, Wisconsin, United States

Full record on ClinicalTrials.gov

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