Neoadjuvant PROSTVAC-VF With or Without Ipilimumab for Prostate Cancer

NCT02506114 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: 14559NCI-2017-01679
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multicentered, open label, randomized phase II trial of PROSTVAC or ipilimumab or the combination of PROSTVAC and ipilimumab as neoadjuvant therapy in patients with localized prostate cancer. Eligible patients will be randomized to PROSTVAC monotherapy (Arm A), ipilimumab monotherapy (Arm B), or combination therapy with both PROSTVAC and ipilimumab (Arm C), prior to RP. In arms A and C, PROSTVAC-V will be administered subcutaneously as the primary vaccine on Day 1, which will be followed 2 weeks later with a series of 2 PROSTVAC-F subcutaneous administrations, given 3 weeks apart. In arms B and C, ipilimumab will be administered twice, at a dose of 3mg/kg, 3 weeks apart. In the combination arm, ipilimumab administration will coincide with the PROSTVAC-F administration. In arm B, ipilimumab will begin on Day 1. In all three arms, radical prostatectomy (RP) will occur 21 days, or three weeks, following final treatment administration of PROSTVAC or ipilimumab. No further therapy will be administered on study following RP.

Conditions

Prostatic Neoplasms

Keywords

prostate

Outcome Measures

Primary Outcomes (1)

• Proportion of Participants With Positive CD3+ T Cell Immune Response

  The proportion of participants who demonstrated a positive response following neoadjuvant therapy as measured by change from baseline in CD3+ T cell infiltration within prostate tumor tissue by immunohistochemistry (IHC) assessment following treatment will be reported. The change in the number of CD3+ T cell infiltration within prostate tissue between the biopsy and radical prostatectomy (RP) specimen will be quantified using immunohistochemistry (IHC),with a positive result if there is \>=2 fold increase in the number of CD3+T cell infiltration.

  Up to 2 years

Secondary Outcomes (4)

• Proportion of Participants With Any Positive Change in Immunologic Infiltration (CD3)

  Up to 2 years

• Proportion of Participants With Any Positive Change in Circulating Effector T Cells

  Up to 2 years

• Proportion of Participants With a Positive Change in Regulatory T Cells

  Up to 2 years

• Number of Participants With Treatment-Related Adverse Events

  Up to 2 years

Study Arms (3)

Arm A: PROSTVAC-V/F

EXPERIMENTAL

PROSTVAC-V: 2 x 10\^8pfu; subcutaneous; Day 1. PROSTVAC-F: 1 x 10\^9pfu; subcutaneous; Days 15, and 36.

Biological: PROSTVAC V/F

Arm B: Ipilimumab Monotherapy

EXPERIMENTAL

Ipilimumab: 3 mg/kg; intravenously; Days 1 and 21.

Drug: Ipilimumab

Arm C: Combined PROSTVAC-V/F + Ipilimumab

EXPERIMENTAL

PROSTVAC-V: 2 x 10\^8pfu; subcutaneous; Day 1. PROSTVAC-F: 1 x 10\^9pfu; subcutaneous; Days 15, and 36. Ipilimumab: 3 mg/kg; intravenously; Days 15 and 36.

Biological: PROSTVAC V/F; Drug: Ipilimumab

Interventions

PROSTVAC V/F BIOLOGICAL

PROSTVAC-V/F is a prostate-specific antigen(PSA)-based immunization strategy. It is intended to generate immune responses to prostate specific antigens and prostate cancer cells. It uses poxviral vectors to introduce modified PSA to the patient in an immunogenic manner to break self-tolerance, and thereby induce immune responses directed against prostate cancer cells.

Arm A: PROSTVAC-V/F; Arm C: Combined PROSTVAC-V/F + Ipilimumab

Ipilimumab DRUG

Arm B: Ipilimumab Monotherapy; Arm C: Combined PROSTVAC-V/F + Ipilimumab

Eligibility Criteria

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

You may qualify if:

• For a subject to be eligible for participation in this study, all of the following criteria must be satisfied:
• Patients must have histologically confirmed adenocarcinoma of the prostate without previous therapy for prostate cancer (PC).
• Treatment-naïve AND
• Undergoing radical prostatectomy (RP) as initial, locally definitive therapy for PC and
• Eligible for RP in a 3 month timeframe AND
• Consentable for RP
• Subject's archival prostate biopsy specimen is available, and subject consents to provide tissue for study endpoint analysis. The prostate biopsy slides or blocks must be available prior to starting any study treatment.
• Age ≥ 18 years
• Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Subject has adequate organ function, defined as:
• White blood cell (WBC) count ≥ 3,000/microliter (mcL)
• Absolute neutrophil count (ANC) ≥ 1,500/mcL
• Platelet count ≥ 100,000/mcL
• Hemoglobin (Hgb) ≥ 10.0 g/dL
• Creatinine ≤ 1.5x institutional upper limit of normal (ULN)

You may not qualify if:

• A subject will not be eligible for participation in this study if any of the following criteria apply.
• Subject's biopsy specimen reveals neuroendocrine or small cell features.
• Subject has any evidence of metastatic disease (pre-operative staging will be undertaken per urologic standard of care) as deemed by the Investigator.
• Subject has prior use of any hormones, including luteinizing hormone-releasing hormone (LHRH) agonists, ketoconazole, antiandrogens (such as bicalutamide, flutamide, or nilutamide), or 5-α-reductase inhibitors.
• Subject has prior use of any anti-cancer treatment or product, such as PC-SPES (or any other PC-x product: PC-HOPE, PC-CARE, PC-PLUS, etc).
• Subject has received prior radiation therapy or chemotherapy for prostate cancer.
• Chronic administration (defined as daily or every other day for continuous use \>14 days) of systemic corticosteroids within 28 days of the first planned dose off PROSTVAC-V/F. Use of inhaled steroids, nasal sprays, and topical creams for small body areas are allowed.
• Active atopic dermatitis or skin condition that disrupts the epidermis
• Inflammatory eye disease requiring steroid treatment
• History of prior solid organ or bone marrow transplant
• Previous history of hypersensitivity to eggs or allergy or untoward reaction to prior vaccinia (smallpox) vaccination.
• Splenectomy
• Subject, or subject's close household contacts (defined as those who share housing or have close physical contact) have any of the following conditions during the screening and/or treatment periods:
• active or a history of atopic dermatitis, eczema or other eczematoid skin disorders that disrupt the epidermis
• other acute, chronic or exfoliative skin conditions (e.g., burns, impetigo, varicella zoster, severe acne or other open rashes or wounds) until condition resolves

Sponsors & Collaborators

• Lawrence Fong: lead
• Bavarian Nordic: collaborator

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Ipilimumab

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

Study was terminated early due to low accrual, thus outcomes are not sufficiently powered for statistical significance.

Results Point of Contact

• Title: Dr. Lawrence Fong, MD
• Organization: University of California, San Francisco

Lawrence.Fong@ucsf.edu

(415) 514-3160

Study Officials

• Lawrence Fong, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, Department of Medicine (Hematology/Oncology)

Study Record Dates

• First Submitted: July 21, 2015
• First Posted: July 22, 2015
• Study Start: October 6, 2016
• Primary Completion: April 22, 2020
• Study Completion: April 22, 2020
• Last Updated: November 24, 2021
• Results First Posted: November 24, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)