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Immunotherapy (Atezolizumab) and Vaccines (MVA-BN-Brachyury and PROSTVAC) for the Treatment of Intermediate-Risk and High-Risk Localized Prostate Cancer, the AtezoVax Study

Trial Status: Active

This trial studies how well atezolizumab, MVA-BN-brachyury and PROSTVAC work for the treatment of intermediate-risk and high-risk localized prostate cancer. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body’s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. PROSTVAC includes the use of two doses; a prime vaccine, PROSTVAC-V (the first vaccine may generate a response from the immune system) and a boost vaccine, PROSTVAC-F (the second vaccine may increase and maintain the response of the immune system). The MVA-BN-brachyury vaccine used with the PROSTVAC vaccine may start an immune response in the tumor. An ‘immune response’ is the process of the body detecting and attacking foreign bodies such as cancer cells. Immune responses are effective in killing some forms of cancer. Giving atezolizumab, MVA-BN-brachyury and PROSTVAC may work better than MVA-BN-brachyury and PROSTVAC alone.

Inclusion Criteria

  • Clinical staged unfavorable intermediate, high-risk or very high-risk prostate cancer per National Comprehensive Cancer Network (NCCN) guidelines
  • Histologically proven prostate adenocarcinoma
  • Patient must be a surgical candidate per the treating investigator’s judgement
  • Easter Cooperative Oncology Group (ECOG) performance status =< 1
  • Absolute neutrophil count (ANC) >= 1.5 × 10^9/L (without granulocyte colony-stimulation factor support within 2 weeks of screening)
  • Platelet count >= 100 × 10^9/L (without platelet transfusion within 2 weeks of screening)
  • Hemoglobin >= 9 g/dL (may not have been transfused within 2 weeks of study treatment initiation)
  • White blood cell count (WBC) >= 2.5 × 10^9/L
  • Total bilirubin level =< 1.5 x the upper limit of normal (ULN) (=< 3 x ULN for subjects with Gilbert’s disease). Patients with a history of unconjugated hyperbilirubinemia with otherwise acceptable liver enzyme levels (as per below criteria) may have higher bilirubin levels
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels =< 2.5 x ULN
  • Urine protein/creatinine ratio (UPCR) =< 2 mg/mg (=< 113.2 mg/mmol) * UPCR can be calculated with either a random spot urine test or a 24-hour test. The 24 urine collection test is more clinically validated, so it is the determining test if there is a discrepancy
  • Serum calculated creatinine clearance >= 50 mL/min using the Cockcroft-Gault equation
  • Highly effective contraception for male subjects throughout the study and for at least 6 months after last study treatment administration if the risk of conception exists
  • Patients must have archival prostate biopsy tissue available with identified prostate cancer. The archival tissue must not have been obtained more than 120 days before enrollment. If none is available, a repeat prostate biopsy is mandatory to be eligible for this study. The repeat biopsy, if performed, must have documented prostate adenocarcinoma
  • Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines
  • Prostate magnetic resonance imaging (MRI) must be performed within the past 240 days

Exclusion Criteria

  • Prostate cancer histology other than adenocarcinoma
  • Previous treatment for prostate cancer
  • Metastatic disease on imaging (computed tomography [CT], MRI, or nuclear bone [NM] bone scan) or through tissue biopsy. This includes nodal metastatic disease. A biopsy is not required to rule out metastasis
  • Use of immunosuppressive medication within 28 days of study treatment initiation, EXCEPT for the following: * Intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); * Systemic corticosteroids at physiologic doses =< 10 mg/day of prednisone or equivalent; * Steroids as premedication for hypersensitivity reactions (e.g. CT scan premedication)
  • Known history of and/or active autoimmune disease requiring systemic treatment. Patients with diabetes mellitus, thyroid disease, vitiligo, or other diseases determined to be not clinically meaningful (per the treating physician) will not be excluded for these conditions
  • Active autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent per treating physician’s clinical judgment. Subjects with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid diseases, or other conditions are eligible
  • The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions: * Cardiovascular disorders: ** Congestive heart failure New York Heart Association class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias within 90 days of study enrollment ** Uncontrolled hypertension defined as sustained blood pressure (BP) > 180 mm Hg systolic or > 120 mm Hg diastolic despite optimal antihypertensive treatment within 2 weeks of starting treatment ** Stroke (including transient ischemic attack [TIA]), myocardial infarction (MI), or other ischemic events, or thromboembolic event (eg, deep venous thrombosis, pulmonary embolism) within 90 days before the first dose * Uncontrolled tumor-related pain as assessed by the treating investigator * Pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently) * Uncontrolled or symptomatic hypercalcemia (ionized calcium > 1.5 mmol/L, calcium > 12 mg/dL or corrected serum calcium > ULN) * Active Tuberculosis
  • Prior allogeneic stem cell or solid organ transplantation
  • Known history of acquired immunodeficiency syndrome
  • Prior or concurrent malignancy whose natural history or treatment, in the opinion of the enrolling investigator, may have the potential to interfere with the safety or efficacy assessment of the investigational regimen
  • Known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening. Patients with a history of HBV or HCV infection are eligible if the viral load is documented as undetectable at screening. Screening tests for HBV, HCV or human immunodeficiency virus (HIV) are not mandatory by the study but will be performed per the discretion of the study investigators
  • Known history of atopic dermatitis or active skin condition (acute chronic, or exfoliative) that disrupts the epidermis that is clinically significant within the past 180 days
  • Known history of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
  • Known history of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
  • Active and inactive vaccinations within 28 days of study treatment initiation. Active vaccinations are prohibited for the duration of the study. Inactive vaccinations are acceptable after the prostatectomy is performed but cannot be given within 1 week of the study vaccine administration
  • Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version [v] 5.0 grade >= 3)
  • Known allergy to eggs, egg products, or aminoglycoside antibiotics (e.g. gentamicin or tobramycin)
  • Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab formulation
  • Known allergy or hypersensitivity to any component of the PROSTVAC or MVA-BN-Brachyury formulation
  • Subjects taking prohibited medications. A washout period of prohibited medications for a period of at least 14 days or as clinically indicated should occur prior to the start of treatment

Utah

Salt Lake City
Huntsman Cancer Institute / University of Utah
Status: ACTIVE
Contact: Benjamin L. Maughan
Phone: 801-213-6147

PRIMARY OBJECTIVES:

I. To measure the relative change in the number of infiltrating CD8+ lymphocytes within the prostate tissue between the paired biopsy and radical prostatectomy specimens.

II. To assess the safety of combination immunotherapy in localized prostate cancer.

SECONDARY OBJECTIVES:

I. To assess the undetectable prostate specific antigen (PSA) rate.

II. Assess the clinical activity of perioperative combination immunotherapy.

EXPLORATORY OBJECTIVES:

I. Determine the pathologic complete response rate compared to matched historical controls.

II. To quantify the difference in tumor immune infiltration cell populations between the prostatectomy and prostate biopsy tissue.

III. To establish a biomarker panel predictive of treatment efficacy which will be validated in future clinical trials.

OUTLINE:

NEOADJUVANT THERAPY: Patients receive atezolizumab intravenously (IV) over 30-60 minutes on day 1, rilimogene galvacirepvec (PROSTVAC-V) subcutaneously (SC) on day 1 of cycle 1, rilimogene glafolivec (PROSTVAC-F) SC on day 1 of cycle 2, and MVA-BN-brachyury-TRICOM vaccine intratumorally (IT) and intraprostatically (IP) on day 1. Treatment repeats every 21 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity.

SURGERY: Within 8 weeks, patients undergo standard of care radical prostatectomy.

ADJUVANT THERAPY: Within 3-8 weeks, patients receive atezolizumab IV over 30-60 minutes and rilimogene glafolivec SC on day 1. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 24 months after prostatectomy.

Trial Phase Phase I/II

Trial Type Treatment

Lead Organization
Huntsman Cancer Institute / University of Utah

Principal Investigator
Benjamin L. Maughan

  • Primary ID HCI121075
  • Secondary IDs NCI-2019-07865
  • Clinicaltrials.gov ID NCT04020094