Perioperative Atezolizumab With MVA-BN-Brachyury and PROSTVAC For Intermediate-Risk And High-Risk Localized Prostate Cancer

NCT04020094 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: HCI121075
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a prospective, open label, single arm phase II trial. A total of 22 patients will be treated with atezolizumab, PROSTVAC, and pre-operative MVA-BN-Brachyury to confirm the efficacy of prostatic combination immunotherapy and to measure the relative change in the number of tumor infiltrating CD8+ lymphocytes within the prostate tissue between the paired biopsy and radical prostatectomy specimens.

Conditions

Prostate Adenocarcinoma

Keywords

intermediate-risk prostate cancer; high-risk prostate cancer; very high-risk prostate cancer

Outcome Measures

Primary Outcomes (2)

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

  CD8+ lymphocytes in diagnostic biopsy and prostatectomy tissue samples will be quantified by immunohistochemistry (IHC) and analyzed using digital quantification. The relative change will be reported.

  Within 8 weeks after cycle2 day 1 visit

• To assess the safety of combination immunotherapy in localized prostate cancer through evaluation of Adverse Events (AEs), Adverse Events of Special Interest (AESIs), and Serious Adverse Events (SAEs)

  Adverse Events (AEs), Adverse Events of Special Interest (AESIs), and Serious Adverse Events (SAEs) as characterized by type, severity (as graded by National Cancer Institute Common Terminology Criteria for Adverse Events \[NCI CTCAE\] v5.0), timing, seriousness, and relationship to study treatment will be documented.

  Lead-in safety evaluation for first 6 subjects is the time from Cycle 1 Day 1 until the start Cycle 3 Day 1(about 63 days) then continuing through completion of the study. From enrollment through completion of the study for the remaining participants

Secondary Outcomes (2)

• To assess the undetectable PSA rate

  6 and 12 months

• Assess clinical activity of perioperative combination immunotherapy.

  PSA evaluation will occur every 3 months after completion of the adjuvant treatment period. PSA relapse-free survival will be calculated and compared to HCI matched historical controls. Patients will be followed for 2 years after prostatectomy.

Study Arms (1)

Treatment: all patients

EXPERIMENTAL

Combination Product: MVA-BN-Brachyury

Interventions

MVA-BN-Brachyury COMBINATION_PRODUCT

Cycle= 21 days. Neoadjuvant Therapy: Treatment will be given for 2 neoadjuvant cycles. MVA-BN-Brachyury will be administered as intratumoral injection on Day 1 of each of 2 neoadjuvant cycles. PROSTVAC-V will be administered as a subq injection on Day 1 of Cycle 1 (the first neoadjuvant cycle) and PROSTVAC-F will be administered as a subq injection on Day 1 of Cycle 2 (the second neoadjuvant cycle). Atezolizumab will be given as an infusion on Day 1 of each 2 neoadjuvant cycles. MVA-BN-Brachyury will be injected intratumorally into the prostate. Injections will target PI-RADS 4 and 5 lesions. Surgery: Patients will undergo SOC radical prostatectomy Adjuvant Therapy: Systemic treatment with atezolizumab and PROSTVAC-F will be reinitiated between 3 to 8 weeks after surgery and will continue for an additional 6 cycles. PROSTVAC-F will be given as a subq injection on Day 1 of each cycle. Atezolizumab will be given as an infusion on Day 1 of each cycle.

Also known as: PROSTVAC, Atezolizumab

Treatment: all patients

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male subjects aged ≥ 18 years.
• Clinical staged unfavorable intermediate, high-risk or very high-risk prostate cancer per NCCN guidelines.
• Histologically proven prostate adenocarcinoma
• Patient must be a surgical candidate
• ECOG Performance Status ≤ 1.
• Adequate organ function as defined as:
• Hematologic:
• Absolute neutrophil count (ANC) ≥ 1.5 × 109/L (without granulocyte colony-stimulation factor support within 2 weeks of screening blood test)
• Platelet count ≥ 100 × 109/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 × 109/L.
• Hepatic:
• Total bilirubin level ≤ 1.5 × the upper limit of normal (ULN) (≤ 3 × ULN for subjects with Gilbert's disease)
• AST and ALT levels ≤ 2.5 × ULN. Patient with a history of unconjugated hyperbilirubinemia with otherwise acceptable liver enzyme levels (as per above criteria) may have higher bilirubin levels.
• Renal:

You may not qualify if:

• Prostate cancer histology other than adenocarcinoma.
• Previous treatment for prostate cancer.
• Metastatic disease on imaging (CT, MRI, or 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 as per 5.2.5.
• The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
• o Cardiovascular disorders:
• Congestive heart failure New York Heart Association Class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias within 3 months 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 event, or thromboembolic event (eg, deep venous thrombosis, pulmonary embolism) within 3 months before first dose.
• Uncontrolled tumor-related pain.

Sponsors & Collaborators

• University of Utah: lead
• Bavarian Nordic: collaborator
• Genentech, Inc.: collaborator

Study Sites (1)

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

MeSH Terms

Interventions

PROSTVAC; atezolizumab

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This study is a prospective, open label, single arm phase II trial.

Study Record Dates

• First Submitted: July 8, 2019
• First Posted: July 15, 2019
• Study Start: November 20, 2019
• Primary Completion: April 9, 2021
• Study Completion: April 9, 2021
• Last Updated: September 22, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)