Rilimogene Galvacirepvec and Recombinant Fowlpox-PSA(L155) / TRICOM Vaccine in Preventing Relapse in Patients with Prostate Cancer after Radical Prostatectomy

Status: Active

Description

This phase II trial studies how well rilimogene galvacirepvec and recombinant fowlpox-prostate specific antigen (PSA)(L155) / triad of costimulatory molecules (B7-1, ICAM-1 and LFA-3) (TRICOM) vaccine work in preventing prostate cancer from coming back in patients who have undergone radical prostatectomy. Vaccines made from a gene-modified virus such as, rilimogene galvacirepvec and recombinant fowlpox-PSA(L155) / TRICOM vaccine, may help the body build an effective immune response to kill tumor cells. Giving vaccine after surgery may kill any remaining tumor cells.

Eligibility Criteria

Inclusion Criteria

  • Completed radical prostatectomy for pathologically-verified adenocarcinoma of the prostate no more than 120 days prior to enrollment; the following procedures are acceptable: radical retropubic prostatectomy (RRP), laparoscopic radical prostatectomy (with or without robotic assistance; LAPD), radical perineal prostatectomy (RPP)
  • Post-operative prostate-specific antigen (PSA) < 0.2 ng/mL by 120 days after prostatectomy
  • Must have one or more of the following: * pT3b or pT4 primary tumor * Gleason score 8-10 * pN1 lymph node disease * Positive surgical margins * Pre-operative PSA of >= 10 ng/mL
  • Patients with pT3a disease who lack one of the above criteria, and who refuse adjuvant radiation, may also be enrolled
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Total bilirubin < 1.5 x upper limit of normal (ULN)
  • Hepatic enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT]) =< 2.5 x ULN
  • Serum sodium, potassium, magnesium, phosphate, and calcium > lower limit of normal (LLN)
  • Serum creatinine =< 1.5 x ULN
  • Hemoglobin >= 9 gm/dL
  • Neutrophil count >= 1000/mcL
  • Platelets >= 100,000/mcL
  • Subject of fathering potential must use an adequate method of contraception to avoid conception throughout the study and for at least 4 weeks after the last dose of study drug to minimize the risk of pregnancy
  • Subjects must have had a negative bone scan, and computed tomography (CT) of abdomen and pelvis within 16 weeks prior to registration; additional forms of imaging (Prostascint scan, magnetic resonance imaging [MRI]) may be substituted for a CT scan of the abdomen and pelvis if clinically indicated
  • ELIGIBILITY FOR THE OPTIONAL SUB-STUDY
  • Patients who are being screened for the therapeutic clinical trial will also be approached for participation into the optional sub-study evaluating sociobiological response to stress; refusal to participate in the sub-study will not impact the patient’s eligibility to participate in the therapeutic intervention * Should a patient consent to the optional sub-study, the patient may proceed with the optional baseline interventions for the optional sub-study as outlined within the protocol’s study calendar

Exclusion Criteria

  • Pure small cell carcinoma of the prostate
  • Radiographically-demonstrable metastases at any time prior to the time of enrollment
  • Diagnosis of cancer requiring systemic therapy in the past 5 years
  • Presence of any major medical condition which, in the opinion of the investigator, precludes participation in the study
  • Neoadjuvant or adjuvant therapy of any kind
  • Chronic administration (defined as daily or every other day for continued use > 14 days) of systemic glucocorticoids within 28 days of the first planned dose of PROSTVAC-V/F; use of inhaled steroids, nasal sprays, and all topical preparations (creams, solutions, gels, ointments, etc.) for up to 5% of the body surface area is allowed
  • Use of systemic immunosuppressant agents including anti-metabolites, glucocorticoids, tumor necrosis factor (TNF) alpha antagonists, antibodies to interleukin (IL) 6 or IL6 receptor (R), calcineurin inhibitors, mammalian target of rapamycin (mTOR) antagonists
  • Prior history of serious toxicity or a systemic reaction to vaccinia immunization such as myopericarditis progressive vaccinia infection, or eczema vaccinatum
  • Inflammatory or exfoliative skin diseases such as eczema, psoriasis that disrupt epidermis
  • Active infections requiring systemic therapy
  • History or serologic evidence of chronic viral infection (hepatitis B or C), human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS)
  • History of allergy to eggs, egg products, aminoglycoside antibiotics
  • History of myocardial disease, such as myocarditis, cardiomyopathy, congestive heart failure, ischemic cardiomyopathy
  • Prior solid organ or stem cell transplant
  • History of or active autoimmune disease (e.g., autoimmune neutropenia, thrombocytopenia, or hemolytic anemia, systemic lupus, localized lupus, Sjogren’s syndrome, scleroderma, myasthenia gravis, Goodpasture’s syndrome, Addison’s disease, Hashimoto’s thyroiditis, or Graves disease); persons with vitiligo are not excluded
  • Uncontrolled diabetes; subjects with diabetes mellitus are not excluded if the condition is well-controlled (glycated hemoglobin [A1C] < 7.5)
  • Vaccination with live attenuated vaccine within 28 days prior to day 1 of PROSTVAC-V/F administration or vaccination with a killed vaccine within 14 days prior to day 1 of PROSTVAC-V/F
  • Inability to avoid close contact or household contact with the following high-risk individuals for three weeks after the day 1 vaccination or until the vaccination site heals completely: (a) children =< 3 years of age, (b) pregnant or nursing women, (c) individuals with prior or concurrent extensive eczema or other eczemoid skin disorders, or (d) immunocompromised individuals, such as those with HIV
  • Any condition which, in the opinion of the investigator, would prevent full participation in this trial (including follow-up), or would interfere with the evaluation of the trial endpoints

Locations & Contacts

South Carolina

Charleston
Medical University of South Carolina
Status: Active
Contact: Michael Brian Lilly
Phone: 843-792-4271
Email: lillym@musc.edu
Ralph H. Johnson Veterans Administration Medical Center
Status: Temporarily closed to accrual
Contact: Michael Brian Lilly
Phone: 843-792-4271
Email: lillym@musc.edu

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To determine if rilimogene galvacirepvec and recombinant fowlpox-PSA(L155)/TRICOM vaccine (PROSTVAC-V/F) has significant anti-tumor effect when used as a post-surgical adjuvant therapy in subjects at high risk of relapse after prostatectomy.

SECONDARY OBJECTIVES:

I. To compare observed relapse free survival (RFS)s for the study population with the predicted RFSs for the study population.

II. To compare the observed RFS with the RFSs of a historical comparison group of Medical University of South Carolina (MUSC) prostatectomy patients.

III. To describe associations between the RFS values and various immunologic, genetic, and biochemical parameters on research blood and tissue specimens.

IV. To describe the toxicity of PROSTVAC-V/F in this patient population.

TERTIARY OBJECTIVES:

I. To evaluate the effects of stress reactivity on the development of an effective anti-tumor immune response in this patient population

II. To evaluate the difference in terms of stress reactivity based on socio-economic status (SES), perceptions of social stressors, and allostatic load (AL) between racial subgroups.

III. To evaluate the difference between racial subgroups for the magnitude and distribution of stress responses with biological (AL) and immunologic measure of vaccine effect.

OUTLINE:

Within 120 days after surgery, patients receive rilimogene galvacirepvec subcutaneously (SC) on day 1 and recombinant fowlpox PSA(L155)/TRICOM vaccine SC on days 15, 28, 57, 85, 113, and 141 in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 2 years.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Prevention

Lead Organization

Lead Organization
Medical University of South Carolina

Principal Investigator
Michael Brian Lilly

Trial IDs

Primary ID 102377
Secondary IDs NCI-2016-01144
Clinicaltrials.gov ID NCT02772562